Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Open accessAbstract
Visceral adipose tissue (VAT) is an important risk factor for obesity-related metabolic disorders. Therefore, a reduction in VAT has become a key goal in obesity management. However, VAT is correlated with intrahepatic triglyceride (IHTG) content, so it is possible that IHTG, not VAT, is a better marker of metabolic disease. We determined the independent association of IHTG and VAT to metabolic function, by evaluating groups of obese subjects, who differed in IHTG content (high or normal) but matched on VAT volume or differed in VAT volume (high or low) but matched on IHTG content. Stable isotope tracer techniques and the euglycemic–hyperinsulinemic clamp procedure were used to assess insulin sensitivity and very-low-density lipoprotein–triglyceride (VLDL-TG) secretion rate. Tissue biopsies were obtained to evaluate cellular factors involved in ectopic triglyceride accumulation. Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower ( P < 0.01), whereas VLDL-triglyceride secretion rate was almost double ( P < 0.001), in subjects with higher than normal IHTG content, matched on VAT. No differences in insulin sensitivity or VLDL-TG secretion were observed between subjects with different VAT volumes, matched on IHTG content. Adipose tissue CD36 expression was lower ( P < 0.05), whereas skeletal muscle CD36 expression was higher ( P < 0.05), in subjects with higher than normal IHTG. These data demonstrate that IHTG, not VAT, is a better marker of the metabolic derangements associated with obesity. Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues.
AI snapshot
Written from the paper’s full text.
TL;DR
In obese nondiabetic adults, intrahepatic triglyceride (IHTG) content, rather than visceral adipose tissue (VAT) volume, was independently linked to multiorgan insulin resistance and increased hepatic VLDL-triglyceride secretion. The authors conclude that VAT’s association with metabolic disease may reflect its correlation with IHTG.
Key findings
- When subjects were matched on VAT volume, those with high IHTG had 41%, 13%, and 36% lower hepatic, adipose tissue, and skeletal muscle insulin sensitivity, respectively (P < 0.01), and nearly double the VLDL-TG secretion rate (23 ± 2 vs. 12 ± 1 µmol/min; P < 0.001).
- When subjects were matched on IHTG content, no differences in insulin sensitivity or VLDL-TG secretion were observed between low- and high-VAT groups.
- In multivariate regression including age, sex, BMI, body fat percentage, IHTG, VAT, and subcutaneous abdominal adipose tissue, IHTG was the best predictor of insulin action in liver, skeletal muscle, and adipose tissue and of VLDL-TG secretion, accounting for 21%, 45%, 38%, and 21% of variability, respectively (P ≤ 0.01); VAT was not a predictor of any dependent variable.
- Skeletal muscle CD36 gene expression was almost 3-fold greater with high IHTG (0.82 ± 0.16 vs. 0.34 ± 0.05 AU; P < 0.05), while adipose tissue CD36 gene expression was 35% lower and adipose CD36 protein was 43% lower in the high-IHTG group.
Methods
- A total of 42 obese men and women were screened; 31 participated (mean BMI 35.7 ± 0.8 kg/m²), with 9 subjects assigned to more than one group. Subjects were nondiabetic and had no liver disease other than NAFLD.
- Groups were matched either on VAT volume with normal vs. high IHTG, or on IHTG content with low vs. high VAT. Body composition was assessed by DXA, MRI, and proton magnetic resonance spectroscopy.
- Metabolic function was assessed with stable isotope tracer techniques and a two-stage euglycemic-hyperinsulinemic clamp; VLDL-TG kinetics were measured with glycerol and palmitate tracers. Adipose and muscle biopsies were used for CD36 gene expression and protein analysis. Comparisons used t tests and stepwise linear regression.
Limitations
- The paper states that the data cannot determine whether the IHTG–metabolic dysfunction association is cause-and-effect, and that insulin resistance could be a cause rather than a consequence of IHTG accumulation; other mechanisms for insulin resistance are also noted.
- The authors state they did not measure CD36 gene expression or protein content in the liver, and instead infer likely hepatic CD36 changes from other studies.
- Evident from the text: the sample was small (31 participants, generally 10 per group), and 9 subjects were assigned to more than one group to achieve matching, which may limit generalizability and independence of group comparisons.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 29 cited sources checked · 0 supported · 0 flagged
- Findingown data
VAT was not a predictor of any of the dependent variables in the multivariate regression.
“VAT was not a predictor of any of the dependent variables.”
Quote in the paperSubstantial claim - Findingown data
Abdominal s.c. adipose tissue CD36 gene expression was 35% lower in the high IHTG than in the normal IHTG group (0.09±0.01 vs 0.14±0.01 AU, P<0.05).
“In contrast, abdominal s.c.adipose tissue CD36 gene expression was 35% lower in the high IHTG than in the normal IHTG group (0.09 Ϯ 0.01 and 0.14 Ϯ 0.01 AU; P Ͻ 0.05) (Fig. 3C)”
Quote in the paperSubstantial claim - Findingown data
Hepatic VLDL-TG secretion rate was almost double in subjects with high than in those with normal IHTG content (23±2 vs 12±1 μmol/min, P<0.001), when matched on VAT volume.
“Hepatic VLDL-TG secretion rate was almost double in subjects with high than in those with normal IHTG content (23 Ϯ 2 and 12 Ϯ 1 mol/min, respectively; P Ͻ 0.001), when matched on VAT volume (Fig. 2A).”
Quote in the paperSubstantial claim - Findingown data
VLDL-TG secretion rate was not different in subjects with low or high VAT volume, when matched on IHTG content.
“However, VLDL-TG secretion rate was not different in subjects with low or high VAT volume, when matched on IHTG content (Fig. 2 A).”
Quote in the paperSubstantial claim - Findingown data
Plasma insulin concentration was inversely correlated with adipose tissue CD36 expression (r=-0.56, P<0.01).
“Plasma insulin concentration was inversely correlated with adipose tissue CD36 expression (r ϭ 0.56, P Ͻ 0.01)”
Quote in the paperNot a substantial claim
- Findingown data§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Skeletal muscle insulin sensitivity was 36% lower in subjects with high IHTG than in those with normal IHTG, matched on VAT.
“Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower (P < 0.01), whereas VLDLtriglyceride secretion rate was almost double (P < 0.001), in subjects with higher than normal IHTG content, matched on VAT.”
Quote in the paperSubstantial claim - Findingown data§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Adipose tissue insulin sensitivity was 13% lower in subjects with high IHTG than in those with normal IHTG, matched on VAT.
“Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower (P < 0.01), whereas VLDLtriglyceride secretion rate was almost double (P < 0.001), in subjects with higher than normal IHTG content, matched on VAT.”
Quote in the paperSubstantial claim - Findingown data
Skeletal muscle CD36 gene expression was almost 3-fold greater in subjects with high IHTG than in those with normal IHTG content, matched on VAT volume (0.82±0.16 vs 0.34±0.05 AU, P<0.05).
“Skeletal muscle CD36 gene expression was almost 3-fold greater in subjects with high IHTG than in those with normal IHTG content, matched on VAT volume (0.82 Ϯ 0.16 and 0.34 Ϯ 0.05 arbitrary units; P Ͻ 0.05) (Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
Adipose tissue CD36 protein content was 43% lower in subjects with high IHTG than in those with normal IHTG (0.19±0.03 vs 0.33±0.05 AU, P<0.05).
“and adipose tissue CD36 protein content was 43% lower in subjects with high IHTG than in those with normal IHTG (0.19 Ϯ 0.03 and 0.33 Ϯ 0.05 AU; P Ͻ 0.05) (Fig. 3D).”
Quote in the paperSubstantial claim - Findingown data
Plasma insulin concentration was directly correlated with muscle insoluble CD36 content (r=0.58, P=0.02).
“and directly correlated with muscle insoluble CD36 content (r ϭ 0.58, P ϭ 0.02).”
Quote in the paperNot a substantial claim - Findingown data
Plasma adiponectin concentration was approximately 50% lower in subjects with high IHTG content than in those with normal IHTG matched on VAT volume.
“Plasma insulin concentration was almost 2-fold greater and plasma adiponectin concentration was Ϸ50% lower in subjects with high IHTG content than in those with normal IHTG who were matched on VAT volume (Table 2).”
Quote in the paperSubstantial claim - Findingown data
Total and detergent-soluble muscle CD36 protein content was not different between any of the subject groups.
“Total and detergent-soluble muscle CD36 protein content was not different between any of our subject groups”
Quote in the paperNot a substantial claim - Findingown data
The absolute secretion rate of VLDL-TG composed of systemic plasma FFA was similar in both the high and the normal IHTG groups (8±1 vs 9±1 μmol/min).
“In contrast, the absolute secretion rate of VLDL-TG composed of systemic plasma FFA was similar in both the high and the normal IHTG groups (8 Ϯ 1 and 9 Ϯ 1 mol/min, respectively) (Fig. 2 A).”
Quote in the paperSubstantial claim - Findingown data
Mean VAT volume in the high-VAT group was 2-fold greater than in the low-VAT group.
“mean VAT volume in the high-VAT group was 2-fold greater than in the low-VAT group (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
Detergent-insoluble CD36 content was 2-fold greater in subjects with high IHTG than in those with normal IHTG content.
“but detergent-insoluble CD36 content was 2-fold greater in subjects with high IHTG than in those with normal IHTG content (Fig. 3B).”
Quote in the paperNot a substantial claim - Findingown data
The secretion rate of VLDL-TG composed of nonsystemic fatty acids was 4-fold greater in subjects with high than with normal IHTG content (14±2 vs 3±1 μmol/min, P<0.001).
“The secretion rate of VLDL-TG composed of nonsystemic fatty acids was 4-fold greater in subjects with high than with normal IHTG content (14 Ϯ 2 and 3 Ϯ 1 mol/min, respectively; P Ͻ 0.001)”
Quote in the paperSubstantial claim - Findingown data
The relative contribution of fatty acids from different sources to total VLDL-TG production was not different between subjects with either low or high VAT volume, when matched on IHTG.
“The relative contribution of fatty acids from different sources to total VLDL-TG production was not different between subjects with either low or high VAT volume, when matched on IHTG (Fig. 2B).”
Quote in the paperSubstantial claim - Findingown data§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Hepatic insulin sensitivity was 41% lower in subjects with high IHTG than in those with normal IHTG, matched on VAT.
“Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower (P < 0.01), whereas VLDLtriglyceride secretion rate was almost double (P < 0.001), in subjects with higher than normal IHTG content, matched on VAT.”
Quote in the paperSubstantial claim - Findingown data
The increase in total VLDL-TG secretion rate in high IHTG subjects was accounted for by the increase in secretion of VLDL-TG composed of nonsystemic fatty acids.
“and accounted for their increase in total VLDL-TG secretion rate (Fig. 2 A).”
Quote in the paperSubstantial claim - Findingown data
The relative contribution of nonsystemic fatty acids incorporated into newly secreted VLDL-TG was much greater in subjects with high than with normal IHTG content (58±4% vs 28±4%, P<0.001).
“The relative contribution of nonsystemic fatty acids incorporated into newly secreted VLDL-TG (presumably derived from lipolysis of intrahepatic and i.p. triglyceride, hepatic lipolysis of circulating triglyceride, and de novo hepatic fatty acid synthesis) was much greater in subjects with high than with normal IHTG content (58 Ϯ 4% and 28 Ϯ 4%, respectively; P Ͻ 0.001) (Fig. 2B).”
Quote in the paperSubstantial claim - Findingown data
Mean IHTG content in the high-IHTG groups was 5-fold greater than in the normal-IHTG groups.
“Mean IHTG content in the high-IHTG groups was 5-fold greater than in the normal-IHTG groups”
Quote in the paperNot a substantial claim - Findingown data
Plasma insulin concentration was almost 2-fold greater in subjects with high IHTG content than in those with normal IHTG matched on VAT volume.
“Plasma insulin concentration was almost 2-fold greater and plasma adiponectin concentration was Ϸ50% lower in subjects with high IHTG content than in those with normal IHTG who were matched on VAT volume (Table 2).”
Quote in the paperSubstantial claim - Findingown data
No differences in insulin sensitivity measures were observed between subjects with low or high VAT volume, when matched on IHTG content.
“However, no differences in insulin sensitivity measures were observed between subjects with low or high VAT volume, when matched on IHTG content (Fig. 1).”
Quote in the paperSubstantial claim - Findingown data
Basal glucose and palmitate kinetics were not different between matched subjects within any of the 2 groups.
“Basal glucose and palmitate kinetics were not different between matched subjects within any of the 2 groups (Table 2).”
Quote in the paperNot a substantial claim - Findingown data
No significant differences in metabolic variables were detected between subjects with low or high VAT volume matched on IHTG content.
“No significant differences in metabolic variables were detected between subjects with low or high VAT volume who were matched on IHTG content (Table 2).”
Quote in the paperSubstantial claim - Findingown data
In the high intrahepatic triglyceride group, intrahepatic triglyceride content was significantly higher than in the normal intrahepatic triglyceride group (25.3 ± 3.5 vs 3.6 ± 0.5 % liver volume, P < 0.01).
“IHTG (% liver volume) | 3.6 Ϯ 0.5 | 25.3 Ϯ 3.5*”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*Value is significantly different from the corresponding value in the normal IHTG group, P Ͻ 0.01.”
Quote in the paperSubstantial claim - Also stated in: § ACKNOWLEDGMENTS. · plain
- Findingown data
In obese subjects matched on visceral adipose tissue volume, those with high intrahepatic triglyceride content had a significantly different relative contribution of nonsystemic fatty acids to VLDL-TG production than those with normal intrahepatic triglyceride content (P < 0.001).
“Very-low-density lipoprotein-triglyceride (VLDL-TG) secretion rate (A) and the relative contribution of systemic (generated primarily by lipolysis of s.c.adipose tissue triglycerides) and nonsystemic fatty acids (generated primarily by lipolysis of intrahepatic triglycerides) to VLDL-TG production (B) in subjects matched on visceral adipose tissue (VAT) volume with either normal or high intrahepat”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*, value is significantly different from corresponding value in the normal IHTG group, P Ͻ 0.001.”
Quote in the paperSubstantial claim - Also stated in: § ACKNOWLEDGMENTS. · plain
- Findingown data
In obese subjects matched on visceral adipose tissue volume, those with high intrahepatic triglyceride content had a significantly different VLDL-TG secretion rate than those with normal intrahepatic triglyceride content (P < 0.001).
“Very-low-density lipoprotein-triglyceride (VLDL-TG) secretion rate (A) and the relative contribution of systemic (generated primarily by lipolysis of s.c.adipose tissue triglycerides) and nonsystemic fatty acids (generated primarily by lipolysis of intrahepatic triglycerides) to VLDL-TG production (B) in subjects matched on visceral adipose tissue (VAT) volume with either normal or high intrahepat”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*, value is significantly different from corresponding value in the normal IHTG group, P Ͻ 0.001.”
Quote in the paperSubstantial claim - Also stated in: § ACKNOWLEDGMENTS. · plain
- Premisecitation
Adipose tissue adiponectin gene expression is decreased in CD36-null mice, demonstrating that adipose tissue CD36 is directly involved in the regulation of adiponectin production.
“Adipose tissue adiponectin gene expression is decreased in CD36null mice, demonstrating that adipose tissue CD36 is directly involved in the regulation of adiponectin production (38).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [38] source
Not checked in the free run.
- Interpretationown data
Our data refute the notion that increased VAT causes metabolic abnormalities associated with obesity.
“Our data refute the notion that increased VAT causes metabolic abnormalities associated with obesity”
Quote in the paperSubstantial claim- Rests on an assumption: A causal link between VAT and metabolic dysfunction has not been demonstrated in humans.
- Interpretationown data
The commonly observed relationship between increased VAT and metabolic disease is because of the correlation between VAT and IHTG.
“and suggest the commonly observed relationship between increased VAT and metabolic disease (1-4) is because of the correlation between VAT and IHTG (8)(9)(10).”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [1] source
Not checked in the free run.
- cites [2] source
Not checked in the free run.
- cites [3] source
Not checked in the free run.
- cites [4] source
Not checked in the free run.
- cites (8)(9)(10)
Not checked in the free run.
- Rests on an assumption: A causal link between VAT and metabolic dysfunction has not been demonstrated in humans.
- Interpretationown data
A more plausible mechanism for ectopic fat accumulation involves alterations in the regulation of FFA uptake from plasma by CD36.
“Our data suggest a more plausible mechanism for ectopic fat accumulation, which involves alterations in the regulation of FFA uptake from plasma by CD36.”
Quote in the paperSubstantial claim- Rests on an assumption: The mechanism responsible for differences in tissue CD36 content is not known.
- Interpretationown data
The results of the present study contradict the prevailing dogma that VAT has deleterious metabolic effects.
“The results of the present study contradict the prevailing dogma that VAT has deleterious metabolic effects (5,6).”
Quote in the paperSubstantial claim0 of 2 sources checked- Rests on an assumption: A causal link between VAT and metabolic dysfunction has not been demonstrated in humans.
- Interpretationown data
IHTG could be directly involved in the pathogenesis of dyslipidemia associated with obesity.
“The data from the present study support the notion that IHTG could be directly involved in the pathogenesis of dyslipidemia associated with obesity (11).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] source
Not checked in the free run.
- Rests on an assumption: The mechanism(s) responsible for the interrelationship among IHTG content, insulin resistance, and hypertriglyceridemia is not known.
- Premisecitation
Hepatic CD36 expression is directly correlated with liver fat in human subjects.
“hepatic CD36 expression is directly correlated with liver fat in human subjects (29).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [29] source
Not checked in the free run.
- Interpretationown data
Alterations in CD36 content in adipose tissue, muscle, and presumably liver might contribute to the association between ectopic fat distribution and obesity-related metabolic disease, by redirecting fatty acid uptake from adipose tissue toward other metabolic organs.
“Alterations in CD36 content in adipose tissue, muscle, and presumably liver might contribute to the association between ectopic fat distribution and obesity-related metabolic disease, by redirecting fatty acid uptake from adipose tissue toward other metabolic organs.”
Quote in the paperNot a substantial claim- Rests on an assumption: The mechanism responsible for differences in tissue CD36 content is not known.
- Interpretationown data
The reported association between VAT and metabolic disease is because of the direct correlation between VAT volume and IHTG content.
“and suggest that the reported association between VAT and metabolic disease is because of the direct correlation between VAT volume and IHTG content.”
Quote in the paperSubstantial claim- Rests on an assumption: A causal link between VAT and metabolic dysfunction has not been demonstrated in humans.
- Interpretationown data
Increased IHTG content is an important marker of the metabolic complications associated with obesity.
“These data underscore the importance of increased IHTG content as a marker of the metabolic complications associated with obesity.”
Quote in the paperSubstantial claim - Premisecitation§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
An increase in IHTG is associated with the same metabolic abnormalities linked to an increase in VAT.
“an increase in IHTG is associated with the same metabolic abnormalities linked to an increase in VAT (9)(10)(11)(12).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites (9)(10)(11)(12)
Not checked in the free run.
- Premisecitation§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
VAT is correlated with intrahepatic triglyceride (IHTG) content.
“VAT correlates directly with intrahepatic triglyceride (IHTG) content (8)(9)(10)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites (8)(9)(10)
Not checked in the free run.
- Interpretationown data
VAT is not an important contributor to the metabolic complications associated with obesity.
“These data demonstrate that VAT is not an important contributor to the metabolic complications associated with obesity”
Quote in the paperSubstantial claim- Rests on an assumption: A causal link between VAT and metabolic dysfunction has not been demonstrated in humans.
- Interpretationown data
The increase in VLDL-TG secretion rate in obese subjects who have NAFLD is primarily caused by the availability of nonsystemic fatty acids derived from lipolysis of IHTG, not VAT.
“Our data suggest that the increase in VLDL-TG secretion rate in obese subjects who have NAFLD is primarily caused by the availability of nonsystemic fatty acids derived from lipolysis of IHTG, not VAT, because VAT volume was the same in both groups and de novo lipogenesis accounts for up to 20% of the fatty acids secreted in VLDL-TG in subjects with NAFLD (39,40).”
Quote in the paperSubstantial claim0 of 2 sources checked- Rests on an assumption: The mechanism(s) responsible for the interrelationship among IHTG content, insulin resistance, and hypertriglyceridemia is not known.
- Interpretationown data
Alterations in cellular fatty acid transport are involved in the pathogenesis of ectopic fat distribution by diverting the accumulation of triglyceride away from adipose tissue and toward other key metabolic organs.
“Our data suggest that alterations in cellular fatty acid transport are involved in the pathogenesis of ectopic fat distribution by diverting the accumulation of triglyceride away from adipose tissue and toward other key metabolic organs.”
Quote in the paperSubstantial claim- Rests on an assumption: The mechanism responsible for differences in tissue CD36 content is not known.
- Interpretationown data
Alterations in cellular fatty acid uptake could be involved in the pathogenesis of ectopic triglyceride accumulation in subjects with NAFLD, by redirecting plasma FFA uptake from adipose tissue toward other tissues.
“the CD36 profile observed in different tissues and subject groups suggests that alterations in cellular fatty acid uptake could be involved in the pathogenesis of ectopic triglyceride accumulation in subjects with nonalcoholic fatty liver disease (NAFLD), by redirecting plasma FFA uptake from adipose tissue toward other tissues.”
- Also stated in: § Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity · hedged
“Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues.”
Quote in the paperSubstantial claim- Rests on an assumption: The mechanism responsible for differences in tissue CD36 content is not known.
- Also stated in: § Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity · hedged
- Interpretationown data
The small amount of triglyceride that accumulates in ectopic organs such as liver and skeletal muscle can be accommodated by the large adipose tissue mass in obese persons.
“However, it is unlikely that the small amount of triglyceride that accumulates in ''ectopic'' organs, such as liver and skeletal muscle, cannot be accommodated by the large adipose tissue mass in obese persons.”
Quote in the paperSubstantial claim- Rests on an assumption: The mechanism responsible for excessive triglyceride accumulation in nonadipose tissues (i.e., ectopic fat) is not known.
- Premisecitation
In vivo secretion rates of most adipokines from VAT are probably not greater than the secretion rates from s.c. adipose tissue.
“In addition, in vivo secretion rates of most adipokines from VAT are probably not greater than the secretion rates from s.c.adipose tissue (22).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
Not checked in the free run.
- Study design and conductown data
The range in visceral adipose tissue volume was similar in the normal and high intrahepatic triglyceride groups.
“The range in VAT volume was similar in both the normal (VAT volume: 689 -3,088 cm 3 ) and the high (VAT volume: 638 -2,702 cm 3 ) IHTG groups.”
Quote in the paperSubstantial claim - Premisecitation
De novo lipogenesis accounts for up to 20% of the fatty acids secreted in VLDL-TG in subjects with NAFLD.
“de novo lipogenesis accounts for up to 20% of the fatty acids secreted in VLDL-TG in subjects with NAFLD (39,40).”
Quote in the paperSubstantial claim0 of 2 sources checked - Study design and conductown data
The normal and high intrahepatic triglyceride groups were matched on visceral adipose tissue volume.
“Group 1 subjects (n ϭ 20) were matched on VAT volume and had either high (Ͼ10% of liver volume) (n ϭ 10) or normal (Յ5.5% of liver volume) (n ϭ 10) IHTG content (Table 1) (41).”
Quote in the paperSubstantial claim - Premisecitation
Increased plasmalemma skeletal muscle CD36 is associated with increased FFA uptake and insulin resistance in animal models and obese and diabetic human subjects.
“The potential importance of CD36 in regulating insulin sensitivity is supported by studies conducted in animal models and in obese and diabetic human subjects that found increased plasmalemma skeletal muscle CD36 was associated with increased FFA uptake and insulin resistance (25,30,31)”
Quote in the paperSubstantial claim0 of 3 sources checked
- May combine two claims. 10
- Classified as probably not a substantial claim. 9
- The quote only partly states this claim. 7
May combine two claims.
Findingown dataNo differences in CD36 adipose tissue gene expression and protein content and in muscle gene expression were detected between subjects with low or high VAT volume, when matched on IHTG content.
“No differences in CD36 adipose tissue gene expression and protein content and in muscle gene expression were detected between subjects with low or high VAT volume, when matched on IHTG content (Fig. 3).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataIn the high visceral adipose tissue group, visceral adipose tissue volume was significantly higher than in the low visceral adipose tissue group (1946 ± 319 vs 766 ± 77 cm3, P < 0.01).
“VAT volume (cm 3 ) | 1290 Ϯ 238 | 1335 Ϯ 178 | 766 Ϯ 77 | 1946 Ϯ 319 †”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“† Value is significantly different from the corresponding value in the low VAT groups, P Ͻ 0.01.”
Quote in the paperNot a substantial claim- Also stated in: § ACKNOWLEDGMENTS. · plain
The quote only partly states this claim.
Findingown dataIn obese subjects matched on visceral adipose tissue volume, those with high intrahepatic triglyceride content had significantly lower hepatic insulin sensitivity than those with normal intrahepatic triglyceride content (P < 0.05).
“Hepatic (A), skeletal muscle (B), and adipose tissue (C) insulin sensitivity in subjects matched on visceral adipose tissue (VAT) volume with either normal or high intrahepatic triglyceride (IHTG) content and subjects matched on IHTG content who had either low or high VAT volume.”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*, value is significantly different from the corresponding value in the normal IHTG group, P Ͻ 0.05.”
Quote in the paperSubstantial claim- Also stated in: § ACKNOWLEDGMENTS. · plain
The quote only partly states this claim.
Findingown dataIn obese subjects matched on visceral adipose tissue volume, those with high intrahepatic triglyceride content had significantly lower adipose tissue insulin sensitivity than those with normal intrahepatic triglyceride content (P < 0.05).
“Hepatic (A), skeletal muscle (B), and adipose tissue (C) insulin sensitivity in subjects matched on visceral adipose tissue (VAT) volume with either normal or high intrahepatic triglyceride (IHTG) content and subjects matched on IHTG content who had either low or high VAT volume.”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*, value is significantly different from the corresponding value in the normal IHTG group, P Ͻ 0.05.”
Quote in the paperSubstantial claim- Also stated in: § ACKNOWLEDGMENTS. · plain
The quote only partly states this claim.
Findingown dataIn obese subjects matched on visceral adipose tissue volume, those with high intrahepatic triglyceride content had significantly lower skeletal muscle insulin sensitivity than those with normal intrahepatic triglyceride content (P < 0.05).
“Hepatic (A), skeletal muscle (B), and adipose tissue (C) insulin sensitivity in subjects matched on visceral adipose tissue (VAT) volume with either normal or high intrahepatic triglyceride (IHTG) content and subjects matched on IHTG content who had either low or high VAT volume.”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*, value is significantly different from the corresponding value in the normal IHTG group, P Ͻ 0.05.”
Quote in the paperSubstantial claim- Also stated in: § ACKNOWLEDGMENTS. · plain
The quote only partly states this claim.
Findingown dataIn obese subjects matched on visceral adipose tissue volume, those with high intrahepatic triglyceride content had significantly different subcutaneous abdominal adipose tissue CD36 gene expression than those with normal intrahepatic triglyceride content (P < 0.05).
“Skeletal muscle (A) and s.c.abdominal adipose tissue (C) CD36 gene expression and skeletal muscle (B) and adipose tissue CD36 protein content (D) in subjects matched on visceral adipose tissue (VAT) volume with either normal or high intrahepatic triglyceride (IHTG) content and in subjects matched on IHTG content who had either low or high VAT volume.”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*, value is significantly different from corresponding value in the normal IHTG group, P Ͻ 0.05.”
Quote in the paperNot a substantial claim- Also stated in: § ACKNOWLEDGMENTS. · plain
The quote only partly states this claim.
Findingown dataIn obese subjects matched on visceral adipose tissue volume, those with high intrahepatic triglyceride content had significantly different skeletal muscle CD36 gene expression than those with normal intrahepatic triglyceride content (P < 0.05).
“Skeletal muscle (A) and s.c.abdominal adipose tissue (C) CD36 gene expression and skeletal muscle (B) and adipose tissue CD36 protein content (D) in subjects matched on visceral adipose tissue (VAT) volume with either normal or high intrahepatic triglyceride (IHTG) content and in subjects matched on IHTG content who had either low or high VAT volume.”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*, value is significantly different from corresponding value in the normal IHTG group, P Ͻ 0.05.”
Quote in the paperSubstantial claim- Also stated in: § ACKNOWLEDGMENTS. · plain
The quote only partly states this claim.
Findingown dataIn obese subjects matched on visceral adipose tissue volume, those with high intrahepatic triglyceride content had significantly different subcutaneous abdominal adipose tissue CD36 protein content than those with normal intrahepatic triglyceride content (P < 0.05).
“Skeletal muscle (A) and s.c.abdominal adipose tissue (C) CD36 gene expression and skeletal muscle (B) and adipose tissue CD36 protein content (D) in subjects matched on visceral adipose tissue (VAT) volume with either normal or high intrahepatic triglyceride (IHTG) content and in subjects matched on IHTG content who had either low or high VAT volume.”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*, value is significantly different from corresponding value in the normal IHTG group, P Ͻ 0.05.”
Quote in the paperNot a substantial claim- Also stated in: § ACKNOWLEDGMENTS. · plain
The quote only partly states this claim.
Findingown dataIn obese subjects matched on visceral adipose tissue volume, those with high intrahepatic triglyceride content had significantly different skeletal muscle CD36 protein content than those with normal intrahepatic triglyceride content (P < 0.05).
“Skeletal muscle (A) and s.c.abdominal adipose tissue (C) CD36 gene expression and skeletal muscle (B) and adipose tissue CD36 protein content (D) in subjects matched on visceral adipose tissue (VAT) volume with either normal or high intrahepatic triglyceride (IHTG) content and in subjects matched on IHTG content who had either low or high VAT volume.”
- Also stated in: § ACKNOWLEDGMENTS. · plain
“*, value is significantly different from corresponding value in the normal IHTG group, P Ͻ 0.05.”
Quote in the paperSubstantial claim- Also stated in: § ACKNOWLEDGMENTS. · plain
Classified as probably not a substantial claim.
PremisecitationIncreased skeletal muscle plasmalemma CD36 content is associated with increased muscle FFA uptake and intramyocellular triglyceride accumulation in human subjects.
“The importance of CD36 in FFA transport and ectopic triglyceride accumulation has been demonstrated by observations in human subjects indicating that increased skeletal muscle plasmalemma CD36 content is associated with increased muscle FFA uptake and intramyocellular triglyceride accumulation (25).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] source
Not checked in the free run.
May combine two claims.
Study design and conductown dataSubjects in each group were matched on age, sex, BMI, and percentage of body fat, but differed in either IHTG content or VAT volume.
“Subjects in each group were matched on age, sex, body mass index (BMI), and percentage of body fat, but differed in either IHTG content or VAT volume (Table 1).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataExcessive IHTG is not only a marker of metabolic dysfunction, but also contributes to the increase in VLDL-TG secretion rate and plasma triglyceride concentration observed in obese persons with NAFLD.
“Therefore, it is possible that excessive IHTG is not only a marker of metabolic dysfunction, but also contributes to the increase in VLDL-TG secretion rate and plasma triglyceride concentration observed in obese persons with NAFLD.”
Quote in the paperSubstantial claim- Rests on an assumption: The mechanism(s) responsible for the interrelationship among IHTG content, insulin resistance, and hypertriglyceridemia is not known.
May combine two claims.
PremisecitationAdiponectin administration decreases IHTG, increases hepatic insulin sensitivity, and reverses obesity-related skeletal muscle insulin resistance.
“Adiponectin administration decreases IHTG (35), increases hepatic insulin sensitivity (36), and reverses obesity-related skeletal muscle insulin resistance (37).”
Quote in the paperNot a substantial claim0 of 3 sources checkedClassified as probably not a substantial claim. May combine two claims.
Premisecitation§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesityAn increase in VAT is associated with impaired glucose tolerance, insulin resistance, and increased VLDL-TG secretion.
“data from metabolic studies conducted on human subjects (3,4) indicate that an increase in VAT is associated with impaired glucose tolerance, insulin resistance, and increased very-low-density lipoproteintriglyceride (VLDL-TG) secretion.”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
Interpretationown dataIHTG content, not VAT volume, is a marker of obesity-related metabolic dysfunction.
“These data demonstrate that IHTG content, not VAT volume, is a marker of obesity-related metabolic dysfunction.”
- Also stated in: § Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity · boosted
“These data demonstrate that IHTG, not VAT, is a better marker of the metabolic derangements associated with obesity.”
Quote in the paperSubstantial claim- Rests on an assumption: A causal link between VAT and metabolic dysfunction has not been demonstrated in humans.
- Also stated in: § Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity · boosted
May combine two claims.
InterpretationcitationFatty acids released from lipolysis of IHTG might stimulate hepatic VLDL-TG production, demonstrating that IHTG in itself could be directly involved in the pathogenesis of dyslipidemia associated with NAFLD.
“In addition, fatty acids released from lipolysis of IHTG might stimulate hepatic VLDL-TG production, demonstrating that IHTG in itself could be directly involved in the pathogenesis of dyslipidemia associated with NAFLD (11).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] source
Not checked in the free run.
- Rests on an assumption: The mechanism(s) responsible for the interrelationship among IHTG content, insulin resistance, and hypertriglyceridemia is not known.
May combine two claims.
Interpretationown dataIncreased IHTG is an independent indicator of multiorgan insulin resistance and increased hepatic secretion of VLDL-TG.
“In summary, increased IHTG is an independent indicator of multiorgan insulin resistance and increased hepatic secretion of VLDL-TG.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenEach subject with normal intrahepatic triglyceride content and a given visceral adipose tissue volume was matched with a subject from the high intrahepatic triglyceride group on visceral adipose tissue within approximately 20% of the normal group's visceral adipose tissue volume.
“Each subject with normal IHTG and a given VAT volume was matched with a subject from the high IHTG group on VAT (within Ϸ20% of VAT volume of the normal IHTG group).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe investigators did not have knowledge of any outcome measures when the matches were performed.
“We did not have knowledge of any outcome measures when the matches were performed.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductown dataIsotopic steady-state conditions were achieved during the final 30 min of the basal period and stages 1 and 2 of the clamp procedure.
“Isotopic steady-state conditions were achieved during the final 30 min of the basal period and stages 1 and 2 of the clamp procedure, so Steele's equation for steady-state conditions was used to calculate substrate kinetics (49).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenSubjects within groups were matched on age, sex, BMI, and percentage of body fat.
“Subjects within groups were matched on age, sex, BMI, and percentage of body fat.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningThe majority of adipokines in the portal vein are derived from s.c. fat, which releases adipokines into the systemic circulation that enter the portal vein through the splanchnic bed.
“Therefore, the majority of adipokines in the portal vein are derived from s.c.fat, which releases adipokines into the systemic circulation that enter the portal vein through the splanchnic bed.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataAll data sets were normally distributed according to the Kolmogorov-Smirnov test.
“All data sets were normally distributed according to the Kolmogorov-Smirnov test, so comparisons between subjects within each group-ing (i.e., between subjects who had the same VAT volume but either normal or high IHTG content and subjects who had the same IHTG content but different VAT volume) were performed by using parametric procedures.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataThe low and high visceral adipose tissue groups were matched on intrahepatic triglyceride content.
“Group 2 subjects (n ϭ 20) were matched on IHTG content and had either low (n ϭ 10) or high (n ϭ 10) VAT volume (Table 1).”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationOnly approximately 20% of portal vein FFA delivered to the liver and 14% of systemic FFA delivered to skeletal muscle are derived from lipolysis of VAT in obese subjects.
“In fact, only Ϸ20% of portal vein FFA delivered to the liver and 14% of systemic FFA delivered to skeletal muscle are derived from lipolysis of VAT in obese subjects (20,21).”
Quote in the paperSubstantial claim0 of 2 sources checked
The paper relies on this without support.
A causal link between VAT and metabolic dysfunction has not been demonstrated in humans.
“Although VAT is associated with metabolic disease, a causal link between VAT and metabolic dysfunction has not been demonstrated in humans.”
The paper relies on this without support.
The mechanism(s) responsible for the interrelationship among IHTG content, insulin resistance, and hypertriglyceridemia is not known.
“The mechanism(s) responsible for the interrelationship among IHTG content, insulin resistance, and hypertriglyceridemia is not known, but could involve redirecting plasma FFA uptake and intracellular triglyceride production from adipose tissue depots to other tissues, such as liver and skeletal muscle, which can impair insulin signaling (13,14) and stimulate VLDL-TG secretion (11).”
The paper relies on this without support.
The mechanism responsible for excessive triglyceride accumulation in nonadipose tissues (i.e., ectopic fat) is not known.
“The mechanism responsible for excessive triglyceride accumulation in nonadipose tissues (i.e., ectopic fat) is not known.”
The paper relies on this without support.
The mechanism responsible for differences in tissue CD36 content is not known.
“The mechanism responsible for differences in tissue CD36 content is not known, but could be related to circulating insulin, because plasma insulin concentration was inversely correlated with adipose tissue CD36 expression and directly correlated with muscle insoluble CD36 content in our subjects.”
The paper relies on this without support.
It is not known whether IHTG or VAT is independently associated with metabolic risk.
“However, it is not known whether IHTG or VAT is independently associated with metabolic risk because both are strongly correlated with each other (8-10).”
The authors state this as an assumption.
Glucose rate of disappearance from plasma was equal to glucose rate of appearance during basal conditions.
“It was assumed that glucose rate of disappearance (Rd) from plasma was equal to glucose rate of appearance (Ra) during basal conditions”
The authors state this as an assumption.
During the clamp procedure, glucose rate of disappearance was equal to the sum of endogenous glucose rate of appearance and the rate of infused glucose.
“during the clamp procedure glucose Rd was assumed to be equal to the sum of endogenous glucose Ra and the rate of infused glucose.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Intrahepatic triglyceride content, not visceral adiposity, is associated with insulin resistance and increased triglyceride secretion.
“Fabbrini and colleagues91 similarly reported that intrahepatic triglyceride content, not visceral adiposity, was associated with insulin resistance and increased triglyceride secretion.”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [91]
Cites
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915 · see citing works
Abdominal obesity and metabolic syndrome
Després, J.-P., & Lemieux, I. (2006) · Nature · doi:10.1038/nature05488 · Cited by 4,354 · see citing works
Donnelly, K. L., Smith, C. I., Schwarzenberg, S. J., Jessurun, J., Boldt, M. D., & Parks, E. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23621 · Cited by 3,604 · see citing works
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714 · see citing works
Nonalcoholic Fatty Liver Disease
Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Bugianesi, E., Lenzi, M., McCullough, A. J., Natale, S., Forlani, G., & Melchionda, N. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1844 · Cited by 2,581 · see citing works
The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
Berg, A. H., Combs, T. P., Du, X., Brownlee, M., & Scherer, P. E. (2001) · Nature Medicine · doi:10.1038/90992 · Cited by 2,526 · see citing works
A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis
Belfort, R., Harrison, S. A., Brown, K., Darland, C., Finch, J., Hardies, J., Balas, B., Gastaldelli, A., Tio, F., Pulcini, J., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa060326 · Cited by 1,827 · see citing works
Molecular mediators of hepatic steatosis and liver injury
Browning, J. D., & Horton, J. D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422422 · Cited by 1,772 · see citing works
INFLUENCES OF GLUCOSE LOADING AND OF INJECTED INSULIN ON HEPATIC GLUCOSE OUTPUT*
Steele, R. D. (1959) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1959.tb44923.x · Cited by 1,680 · see citing works
Szczepaniak, L. S., Nurenberg, P., Leonard, D. S., Browning, J. D., Reingold, J. S., Grundy, S. M., Hobbs, H. H., & Dobbins, R. L. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00064.2004 · Cited by 1,562 · see citing works
Visceral fat adipokine secretion is associated with systemic inflammation in obese humans
Fontana, L., Eagon, J. C., Trujillo, M. E., Scherer, P. E., & Klein, S. (2007) · Diabetes · doi:10.2337/db06-1656 · Cited by 1,417 · see citing works
Self-citationObesity-associated improvements in metabolic profile through expansion of adipose tissue
Kim, J.-Y., van de Wall, E., Laplante, M., Azzara, A., Trujillo, M. E., Hofmann, S. M., Schraw, T., Durand, J. L., Li, H., Li, G., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31021 · Cited by 1,310 · see citing works
Xu, A., Wang, Y., Keshaw, H., Xu, L. Y., Lam, K. S. L., & Cooper, G. J. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17797 · Cited by 1,298 · see citing works
Xu, A., Wang, Y., Keshaw, H., Xu, L. Y., Lam, K. S. L., & Cooper, G. J. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317797 · Cited by 1,298 · see citing works
Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease.
Després, J. P., Moorjani, S., Lupien, P. J., Tremblay, A., Nadeau, A., & Bouchard, C. (1990) · Arteriosclerosis: An Official Journal of the American Heart Association, Inc. · doi:10.1161/01.atv.10.4.497 · Cited by 1,248 · see citing works
Splanchnic lipolysis in human obesity
Nielsen, S., Guo, Z., Johnson, C. M., Hensrud, D. D., & Jensen, M. D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21047 · Cited by 933 · see citing works
Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease
Klein, S., Fontana, L., Young, V. L., Coggan, A. R., Kilo, C., Patterson, B. W., & Mohammed, B. S. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa033179 · Cited by 909 · see citing works
Self-citationBoden, G. H. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.06.007 · Cited by 853 · see citing works
Measurement of Size and Turnover Rate of Body Glucose Pool by the Isotope Dilution Method
Steele, R., Wall, J. S., de Bodo, R. C., & Altszuler, N. (1956) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1956.187.1.15 · Cited by 816 · see citing works
Groop, L. C., Bonadonna, R. C., DelPrato, S., Ratheiser, K., Zyck, K., Ferrannini, E., & DeFronzo, R. A. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114142 · Cited by 812 · see citing works
Overproduction of large VLDL particles is driven by increased liver fat content in man
Adiels, M., Taskinen, M.-R., Packard, C., Caslake, M. J., Soro-Paavonen, A., Westerbacka, J., Vehkavaara, S., Häkkinen, A., Olofsson, S.-O., Yki-Järvinen, H., et al. (2006) · Diabetologia · doi:10.1007/s00125-005-0125-z · Cited by 690 · see citing works
Fabbrini, E., Mohammed, B. S., Magkos, F., Korenblat, K. M., Patterson, B. W., & Klein, S. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.11.038 · Cited by 631 · see citing works
Self-citationKorenblat, K. M., Fabbrini, E., Mohammed, B. S., & Klein, S. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.01.075 · Cited by 592 · see citing works
Self-citationLewis, G., Uffelman, K., Szeto, L., Weller, B., & Steiner, G. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117633 · Cited by 533 · see citing works
Regulation of fatty acid uptake into tissues: lipoprotein lipase- and CD36-mediated pathways
Goldberg, I. J., Eckel, R. H., & Abumrad, N. A. (2008) · Journal of Lipid Research · doi:10.1194/jlr.r800085-jlr200 · Cited by 436 · see citing works
Self-citationDiraison, F., Moulin, P., & Beylot, M. (2003) · Diabetes & Metabolism · doi:10.1016/s1262-3636(07)70061-7 · Cited by 435 · see citing works
Gene expression in human NAFLD
Greco, D., Kotronen, A., Westerbacka, J., Puig, O., Arkkila, P., Kiviluoto, T., Laitinen, S., Kolak, M., Fisher, R. M., Hamsten, A., et al. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00074.2008 · Cited by 427 · see citing works
Heilbronn, L. K., Smith, S. R., & Ravussin, É. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802853 · Cited by 411 · see citing works
Bonen, A., Parolin, M. L., Steinberg, G. R., Calles‐Escandon, J., Tandon, N. N., Glatz, J. F. C., Luiken, J. J. F. P., Heigenhauser, G. J. F., & Dyck, D. J. (2004) · The FASEB Journal · doi:10.1096/fj.03-1065fje · Cited by 410 · see citing works
Why Visceral Fat is Bad: Mechanisms of the Metabolic Syndrome
Bergman, R. N., Kim, S. P., Catalano, K. J., Hsu, I. R., Chiu, J. D., Kabir, M., Hucking, K., & Ader, M. (2006) · Obesity · doi:10.1038/oby.2006.277 · Cited by 371 · see citing works
Janssen, I., Fortier, A., Hudson, R., & Ross, R. (2002) · Diabetes Care · doi:10.2337/diacare.25.3.431 · Cited by 326 · see citing works
Influence of body fat content and distribution on variation in metabolic risk
Vega, G. L., Adams-Huet, B., Peshock, R., Willett, D., Shah, B., & Grundy, S. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0814 · Cited by 312 · see citing works
Metabolic Effects of Visceral Fat Accumulation in Type 2 Diabetes
Gastaldelli, A., Miyazaki, Y., Pettiti, M., Matsuda, M., Mahankali, S., Santini, E., DeFronzo, R. A., & Ferrannini, E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020696 · Cited by 289 · see citing works
Increased Rates of Fatty Acid Uptake and Plasmalemmal Fatty Acid Transporters in Obese Zucker Rats
Luiken, J. J. F. P., Arumugam, Y., Dyck, D. J., Bell, R. C., Pelsers, M. M. L., Turcotte, L. P., Tandon, N. N., Glatz, J. F. C., & Bonen, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100052200 · Cited by 282 · see citing works
The Insulin Resistance—Dyslipidemic Syndrome of Visceral Obesity: Effect on Patients' Risk
Després, J. (1998) · Obesity Research · doi:10.1002/j.1550-8528.1998.tb00683.x · Cited by 261 · see citing works
Luiken, J. J. F. P., Koonen, D. P. Y., Willems, J., Zorzano, A., Becker, C., Fischer, Y., Tandon, N. N., van der Vusse, G. J., Bonen, A., & Glatz, J. F. C. (2002) · Diabetes · doi:10.2337/diabetes.51.10.3113 · Cited by 260 · see citing works
Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle
Koonen, D. P. Y., Glatz, J. F. C., Bonen, A., & Luiken, J. J. F. P. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.08.018 · Cited by 238 · see citing works
Muscle Oxidative Capacity Is a Better Predictor of Insulin Sensitivity than Lipid Status
Bruce, C. R., Anderson, M. J., Carey, A. L., Newman, D. G., Bonen, A., Kriketos, A. D., Cooney, G. J., & Hawley, J. A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030791 · Cited by 234 · see citing works
Insulin Resistance Accelerates a Dietary Rat Model of Nonalcoholic Steatohepatitis
Ota, T., Takamura, T., Kurita, S., Matsuzawa, N., Kita, Y., Uno, M., Akahori, H., Misu, H., Sakurai, M., Zen, Y., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.10.014 · Cited by 227 · see citing works
The case of visceral fat: argument for the defense
Klein, S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422028 · Cited by 206 · see citing works
Self-citationHwang, J.-H., Stein, D. T., Barzilai, N., Cui, M.-H., Tonelli, J., Kishore, P., & Hawkins, M. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00590.2006 · Cited by 188 · see citing works
Abdominal Obesity and Fatty Liver
Jakobsen, M. U., Berentzen, T. L., Sørensen, T. I. A., & Overvad, K. (2007) · Epidemiologic Reviews · doi:10.1093/epirev/mxm002 · Cited by 180 · see citing works
Opposite Regulation of CD36 Ubiquitination by Fatty Acids and Insulin
Smith, J., Su, X., El-Maghrabi, R. M., Stahl, P. D., & Abumrad, N. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800008200 · Cited by 145 · see citing works
Self-citationLipid metabolism response to a single, prolonged bout of endurance exercise in healthy young men.
Magkos, F., Wright, D. C., Patterson, B. W., Mohammed, B., & Mittendorfer, B. (2006) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00259.2005 · Cited by 140 · see citing works
Self-citationValidation of a new procedure to determine plasma fatty acid concentration and isotopic enrichment
Patterson, B. W., Zhao, G., Elias, N., Hachey, D. L., & Klein, S. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32435-4 · Cited by 125 · see citing works
Self-citationPatterson, B. W., Mittendorfer, B., Elias, N., Satyanarayana, R., & Klein, S. (2002) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)30164-4 · Cited by 118 · see citing works
Self-citationLong-Chain Fatty Acid Uptake into Adipocytes Depends on Lipid Raft Function
Pohl, J., Ring, A., Ehehalt, R., Schulze‐Bergkamen, H., Schad, A., Verkade, P., & Stremmel, W. (2004) · Biochemistry · doi:10.1021/bi035743m · Cited by 114 · see citing works
CD36-Facilitated Fatty Acid Uptake Inhibits Leptin Production and Signaling in Adipose Tissue
Hajri, T., Hall, A. M., Jensen, D. R., Pietka, T. A., Drover, V. A., Tao, H., Eckel, R., & Abumrad, N. A. (2007) · Diabetes · doi:10.2337/db06-1699 · Cited by 111 · see citing works
Self-citationEffect of weight loss on VLDL-triglyceride and apoB-100 kinetics in women with abdominal obesity
Mittendorfer, B., Patterson, B. W., & Klein, S. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00379.2002 · Cited by 90 · see citing works
Self-citationEhehalt, R., Sparla, R., Kulaksiz, H., Herrmann, T., Füllekrug, J., & Stremmel, W. (2008) · BMC Cell Biology · doi:10.1186/1471-2121-9-45 · Cited by 88 · see citing works
Kolak, M., Yki‐Järvinen, H., Kannisto, K., Tiikkainen, M., Hamsten, A., Eriksson, P. O., & Fisher, R. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1465 · Cited by 86 · see citing works
Magkos, F., Patterson, B. W., & Mittendorfer, B. (2007) · Journal of Lipid Research · doi:10.1194/jlr.d600048-jlr200 · Cited by 53 · see citing works
Self-citationAssessment of Intrahepatic Triglyceride Content Using Magnetic Resonance Spectroscopy
Frimel, T. N., Deivanayagam, S., Bashir, A., O'Connor, R. A., & Klein, S. (2007) · Journal of the CardioMetabolic Syndrome · doi:10.1111/j.1559-4564.2007.07168.x · Cited by 42 · see citing works
Self-citationPelsers, M. M. A. L., Tsintzas, K., Boon, H., Jewell, K., Norton, L., Luiken, J. J. F. P., Glatz, J. F. C., & van Loon, L. J. C. (2007) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01698.x · Cited by 25 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
Pathophysiology of human visceral obesity: an update
Tchernof, A., & Després, J.-P. (2013) · Physiological Reviews · doi:10.1152/physrev.00033.2011 · Cited by 2,583 · see citing works
Inflammatory links between obesity and metabolic disease
Lumeng, C. N., & Saltiel, A. R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57132 · Cited by 2,319 · see citing works
Mechanisms for Insulin Resistance: Common Threads and Missing Links
Samuel, V. T., & Shulman, G. I. (2012) · Cell · doi:10.1016/j.cell.2012.02.017 · Cited by 2,294 · see citing works
Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications
Fabbrini, E., Sullivan, S., & Klein, S. (2010) · Hepatology · doi:10.1002/hep.23280 · Cited by 2,100 · see citing works
Self-citationObesity Phenotypes, Diabetes, and Cardiovascular Diseases
Piché, M., Tchernof, A., & Després, J. (2020) · Circulation Research · doi:10.1161/circresaha.120.316101 · Cited by 2,046 · see citing works
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002 · see citing works
Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics
Puchalska, P., & Crawford, P. A. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.022 · Cited by 1,617 · see citing works
Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement
Neeland, I. J., Ross, R., Després, J.-P., Matsuzawa, Y., Yamashita, S., Shai, I., Seidell, J., Magni, P., Santos, R. D., Arsenault, B., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30084-1 · Cited by 1,603 · see citing works
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529 · see citing works
Body Fat Distribution and Risk of Cardiovascular Disease: An Update
Després, J.-P. (2012) · Circulation · doi:10.1161/circulationaha.111.067264 · Cited by 1,481 · see citing works
Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease
Ipsen, D. H., Lykkesfeldt, J., & Tveden-Nyborg, P. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2860-6 · Cited by 1,471 · see citing works
Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome
Yki‐Järvinen, H. (2014) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70032-4 · Cited by 1,260 · see citing works
Lipid-induced insulin resistance: unravelling the mechanism
Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60408-4 · Cited by 1,189 · see citing works
González‐Muniesa, P., Martínez‐González, M. Á., Hu, F. B., Després, J., Matsuzawa, Y., Loos, R. J. F., Moreno, L. A., Bray, G. A., & Martínez, J. A. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.34 · Cited by 1,142 · see citing works
Insulin Resistance: From Mechanisms to Therapeutic Strategies
Lee, S.-H., Park, S., & Choi, C. S. (2021) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2021.0280 · Cited by 1,179 · see citing works
Assessing Adiposity: A Scientific Statement From the American Heart Association
Cornier, M.-A., Després, J.-P., Davis, N., Grossniklaus, D. A., Klein, S., Lamarche, B., Lopez-Jimenez, F., Rao, G., St-Onge, M.-P., Towfighi, A., et al. (2011) · Circulation · doi:10.1161/cir.0b013e318233bc6a · Cited by 945 · see citing works
Self-citationWhy does obesity cause diabetes?
Klein, S., Gastaldelli, A., Yki-Järvinen, H., & Scherer, P. E. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.012 · Cited by 939 · see citing works
Self-citationCusi, K. J. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.02.003 · Cited by 912 · see citing works
Metabolically healthy obesity: Epidemiology, mechanisms, and clinical implications
Stefan, N., Häring, H.-U., Hu, F. B., & Schulze, M. B. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70062-7 · Cited by 857 · see citing works
Stefan, N., Häring, H., & Cusi, K. J. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30154-2 · Cited by 848 · see citing works
Gaggini, M., Morelli, M., Buzzigoli, E., DeFronzo, R. A., Bugianesi, E., & Gastaldelli, A. (2013) · Nutrients · doi:10.3390/nu5051544 · Cited by 824 · see citing works
Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease
Smith, G. I., Shankaran, M., Yoshino, M., Schweitzer, G. G., Chondronikola, M., Beals, J. W., Okunade, A. L., Patterson, B. W., Nyangau, E., Field, T., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci134165 · Cited by 771 · see citing works
Self-citationThe role of fructose in the pathogenesis of NAFLD and the metabolic syndrome
Lim, J. S., Mietus-Snyder, M., Valente, A., Schwarz, J.-M., & Lustig, R. H. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.41 · Cited by 771 · see citing works
Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases
Samuel, V. T., & Shulman, G. I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.002 · Cited by 745 · see citing works
“And intrahepatic lipid content, not VATmass, better relates tomeasures of hepatic insulin sensitivity (Fabbrini et al., 2009), even in patients with marked obesity (Magkos et al., 2010).”
Nonalcoholic Fatty Liver Disease, Hepatic Insulin Resistance, and Type 2 Diabetes
Birkenfeld, A. L., & Shulman, G. I. (2013) · Hepatology · doi:10.1002/hep.26672 · Cited by 740 · see citing works
Ballestri, S., Zona, S., Targher, G., Romagnoli, D., Baldelli, E., Nascimbeni, F., Roverato, A., Guaraldi, G., & Lonardo, A. (2015) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.13264 · Cited by 717 · see citing works
Cobbina, E., & Akhlaghi, F. (2017) · Drug Metabolism Reviews · doi:10.1080/03602532.2017.1293683 · Cited by 660 · see citing works
Adiposity and cancer risk: new mechanistic insights from epidemiology
Renehan, A. G., Zwahlen, M., & Egger, M. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3967 · Cited by 654 · see citing works
The many faces of diabetes: a disease with increasing heterogeneity
Tuomilehto, J., Santoro, N., Caprio, S., Cai, M., Weng, J., & Groop, L. (2013) · The Lancet · doi:10.1016/s0140-6736(13)62219-9 · Cited by 652 · see citing works
Metabolically healthy obesity: facts and fantasies
Smith, G. I., Mittendorfer, B., & Klein, S. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129186 · Cited by 653 · see citing works
Self-citationMetabolic-associated fatty liver disease and lipoprotein metabolism
Heeren, J., & Scheja, L. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101238 · Cited by 666 · see citing works
Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism
Pepino, M. Y., Kuda, O., Samovski, D., & Abumrad, N. A. (2014) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071812-161220 · Cited by 643 · see citing works
Self-citationCharacterizing the profile of obese patients who are metabolically healthy
Primeau, V., Coderre, L., Karelis, A. D., Brochu, M., Lavoie, M.-È., Messier, V., SLADEK, R. M., & RABASA-LHORET, R. P. R. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.216 · Cited by 630 · see citing works
Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance
Meex, R. C. R., & Watt, M. J. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.56 · Cited by 631 · see citing works
A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism
Herman, M. A., Peroni, O. D., Villoria, J., Schön, M. R., Abumrad, N. A., Blüher, M., Klein, S., & Kahn, B. B. (2012) · Nature · doi:10.1038/nature10986 · Cited by 599 · see citing works
Self-citationSeidah (2014) · doi:10.1161/circresaha.114.301621 · Cited by 596 · see citing works
Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans
Stefan, N., Schick, F., & Häring, H.-U. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.008 · Cited by 575 · see citing works
Goodpaster, B. H., DeLany, J. P., Otto, A. D., Kuller, L., Vockley, J., South-Paul, J. E., Thomas, S. B., Brown, J., McTigue, K., Hames, K. C., et al. (2010) · JAMA · doi:10.1001/jama.2010.1505 · Cited by 558 · see citing works
Contribution of adipogenesis to healthy adipose tissue expansion in obesity
Vishvanath, L., & Gupta, R. K. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129191 · Cited by 558 · see citing works
The role of fatty acids in insulin resistance
Sears, B., & Perry, M. (2015) · Lipids in Health and Disease · doi:10.1186/s12944-015-0123-1 · Cited by 551 · see citing works
Role of Estrogens in the Regulation of Liver Lipid Metabolism
Palmisano, B. T., Zhu, L., & Stafford, J. M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-70178-3_12 · Cited by 550 · see citing works
The role of adipose tissue in cardiovascular health and disease
Oikonomou, E. K., & Antoniades, C. A. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0097-6 · Cited by 509 · see citing works
The role of hepatokines in metabolism
Stefan, N., & Häring, H.-U. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.258 · Cited by 500 · see citing works
Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor?
Bhatia, L. S., Curzen, N. P., Calder, P. C., & Byrne, C. D. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehr453 · Cited by 497 · see citing works
Bjermo, H., Iggman, D., Kullberg, J., Dahlman, I., Johansson, L., Persson, L., Berglund, J., Pulkki, K., Basu, S., Uusitupa, M., et al. (2012) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.030114 · Cited by 490 · see citing works
Pathology of nonalcoholic fatty liver disease
Brunt, E. M. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.21 · Cited by 484 · see citing works
Manco, M., Putignani, L., & Bottazzo, G. F. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0030 · Cited by 479 · see citing works
Lomonaco, R., Ortiz‐Lopez, C., Orsak, B., Webb, A., Hardies, J., Darland, C., Finch, J., Gastaldelli, A., Harrison, S. A., Tio, F. O., et al. (2011) · Hepatology · doi:10.1002/hep.25539 · Cited by 461 · see citing works
Obesity and the risk of cardiometabolic diseases
Valenzuela, P. L., Carrera-Bastos, P., Castillo-García, A., Lieberman, D. E., Santos-Lozano, A., & Lucia, A. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00847-5 · Cited by 452 · see citing works
Role of Insulin Resistance in MAFLD
Sakurai, Y., Kubota, N., Yamauchi, T., & Kadowaki, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084156 · Cited by 448 · see citing works
New insights into the pathophysiology of dyslipidemia in type 2 diabetes
Taskinen, M.-R., & Borén, J. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.01.039 · Cited by 440 · see citing works
Rosqvist, F., Iggman, D., Kullberg, J., Cedernaes, J., Johansson, H.-E., Larsson, A., Johansson, L., Ahlström, H., Arner, P., Dahlman, I., et al. (2014) · Diabetes · doi:10.2337/db13-1622 · Cited by 429 · see citing works
Sex Differences in Lipid and Lipoprotein Metabolism: It's Not Just about Sex Hormones
Wang, X., Magkos, F., & Mittendorfer, B. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2061 · Cited by 423 · see citing works
Self-citationEctopic Fat Depots and Cardiovascular Disease
Britton, K. A., & Fox, C. S. (2011) · Circulation · doi:10.1161/circulationaha.111.077602 · Cited by 418 · see citing works
NAFLD: Mechanisms, Treatments, and Biomarkers
Nassir, F. (2022) · Biomolecules · doi:10.3390/biom12060824 · Cited by 422 · see citing works
Mechanisms of Glucocorticoid-Induced Insulin Resistance
Geer, E. B., Islam, J., & Buettner, C. (2014) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.10.005 · Cited by 392 · see citing works
Yoshino, J., Conte, C., Fontana, L., Mittendorfer, B., Imai, S., Schechtman, K. B., Gu, C. C., Kunz, I., Fanelli, F. R., Patterson, B. W., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.09.015 · Cited by 381 · see citing works
Self-citationContribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus
Burhans, M. S., Hagman, D. K., Kuzma, J. N., Schmidt, K. A., & Kratz, M. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170040 · Cited by 427 · see citing works
Roles of diacylglycerols and ceramides in hepatic insulin resistance
Petersen, M. C., & Shulman, G. I. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.04.004 · Cited by 373 · see citing works
Fructose and metabolic diseases: New findings, new questions
Tappy, L., Lê, K., Tran, C., & Paquot, N. (2010) · Nutrition · doi:10.1016/j.nut.2010.02.014 · Cited by 365 · see citing works
Role of Mitochondria in Nonalcoholic Fatty Liver Disease
Nassir, F., & Ibdah, J. A. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15058713 · Cited by 359 · see citing works
Mammalian Triacylglycerol Metabolism: Synthesis, Lipolysis, and Signaling
Coleman, R., & Mashek, D. G. (2011) · Chemical Reviews · doi:10.1021/cr100404w · Cited by 332 · see citing works
Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans
Pafili, K., & Roden, M. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101122 · Cited by 330 · see citing works
Zhu, L., Brown, W. C., Cai, Q., Krust, A., Chambon, P., McGuinness, O. P., & Stafford, J. M. (2013) · Diabetes · doi:10.2337/db11-1718 · Cited by 326 · see citing works
Okamura, T., Hashimoto, Y., Hamaguchi, M., Obora, A., Kojima, T., & Fukui, M. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0076-3 · Cited by 325 · see citing works
Epigenetic Regulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease
Sookoian, S. C., Rosselli, M. S., Gemma, C., Burgueño, A. L., Gianotti, T. F., Castaño, G. O., & Pirola, C. J. (2010) · Hepatology · doi:10.1002/hep.23927 · Cited by 320 · see citing works
Pathogenesis and Prevention of Hepatic Steatosis.
Nassir, F., Rector, R. S., Hammoud, G. M., & Ibdah, J. A. (2015) · PubMed Central · Cited by 321 · see citing works
Diacylglycerol Activation of Protein Kinase Cε and Hepatic Insulin Resistance
Jornayvaz, F. R., & Shulman, G. I. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.005 · Cited by 315 · see citing works
Type 2 Diabetes in Youth: Epidemiology and Pathophysiology
D’Adamo, E., & Caprio, S. (2011) · Diabetes Care · doi:10.2337/dc11-s212 · Cited by 315 · see citing works
Oleanolic Acid: Extraction, Characterization and Biological Activity
Castellano, J. M., Ramos‐Romero, S., & Perona, J. S. (2022) · Nutrients · doi:10.3390/nu14030623 · Cited by 324 · see citing works
Effect of aerobic exercise training dose on liver fat and visceral adiposity
Keating, S. E., Hackett, D. A., Parker, H. M., O’Connor, H. T., Gerofi, J. A., Sainsbury, A., Baker, M. K., Chuter, V. H., Caterson, I. D., George, J., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.022 · Cited by 313 · see citing works
Haufe, S., Engeli, S., Kast, P., Böhnke, J., Utz, W., Haas, V., Hermsdorf, M., Mähler, A., Wiesner, S., Birkenfeld, A. L., et al. (2011) · Hepatology · doi:10.1002/hep.24242 · Cited by 307 · see citing works
Lifestyle and the Prevention of Type 2 Diabetes: A Status Report
Galaviz, K. I., Narayan, K. M. V., Lobelo, F., & Weber, M. B. (2015) · American Journal of Lifestyle Medicine · doi:10.1177/1559827615619159 · Cited by 324 · see citing works
New obesity classification criteria as a tool for bariatric surgery indication
LORENZO, A. D. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i2.681 · Cited by 312 · see citing works
What is metabolic syndrome, and why are children getting it?
Weiss, R., Bremer, A. A., & Lustig, R. H. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12030 · Cited by 306 · see citing works
Targher, G., & Byrne, C. D. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3093 · Cited by 298 · see citing works
Müller, M. J., Lagerpusch, M., Enderle, J., Schautz, B., Heller, M., & Bosy‐Westphal, A. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01033.x · Cited by 292 · see citing works
Dietary carbohydrates and fats in nonalcoholic fatty liver disease
Yki-Järvinen, H., Luukkonen, P. K., Hodson, L., & Moore, J. B. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00472-y · Cited by 294 · see citing works
Sookoian, S. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i29.3775 · Cited by 281 · see citing works
Fabbrini, E., Cella, M., McCartney, S. A., Fuchs, A. G., Abumrad, N. A., Pietka, T., Chen, Z., Finck, B. N., Han, D. H., Magkos, F., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.04.010 · Cited by 280 · see citing works
Self-citationGepner, Y., Shelef, I., Schwarzfuchs, D., Zelicha, H., Tene, L., Yaskolka Meir, A., Tsaban, G., Cohen, N., Bril, N., Rein, M., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.030501 · Cited by 279 · see citing works
Hocking, S. L., Samocha-Bonet, D., Milner, K.-L., Greenfield, J., & Chisholm, D. (2013) · Endocrine reviews · doi:10.1210/er.2012-1041 · Cited by 261 · see citing works
Schwarz, J., Noworolski, S. M., Erkin‐Cakmak, A., Korn, N. J., Wen, M., Tai, V., Jones, G. M., Palii, S. P., Velasco-Alin, M., Pan, K. D. H., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.05.043 · Cited by 272 · see citing works
Self-citationFetuin B is a secreted hepatocyte factor linking steatosis to impaired glucose metabolism
Meex, R. C., Hoy, A. J., Morris, A., Brown, R. D., Lo, J. C. Y., Burke, M., Goode, R. J. A., Kingwell, B. A., Kraakman, M. J., Febbraio, M. A., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.023 · Cited by 255 · see citing works
Gastric bypass and banding equally improve insulin sensitivity and β cell function
Bradley, D., Conte, C., Mittendorfer, B., Eagon, J. C., Varela, J. E., Fabbrini, E., Gastaldelli, A., Chambers, K. T., Su, X., Okunade, A., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64895 · Cited by 244 · see citing works
Self-citationCefalu, W. T., Bray, G. A., Home, P., Garvey, W. T., Klein, S., Pi-Sunyer, X., Hu, F. B., Raz, I., Gaal, L. V., Wolfe, B. M., et al. (2015) · Diabetes Care · doi:10.2337/dc15-1081 · Cited by 245 · see citing works
Self-citationMcManaman, J. L., Bales, E. S., Orlicky, D. J., Jackman, M. R., MacLean, P. S., Cain, S., Crunk, A. E., Mansur, A., Graham, C. E., Bowman, T. A., et al. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m035063 · Cited by 241 · see citing works
Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity
Sen, T., Cawthon, C. R., Ihde, B. T., Hajnal, A., DiLorenzo, P. M., de La Serre, C. B., & Czaja, K. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.02.027 · Cited by 239 · see citing works
Gepner, Y., Shelef, I., Komy, O., Cohen, N., Schwarzfuchs, D., Bril, N., Rein, M., Serfaty, D., Kenigsbuch, S., Zelicha, H., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.04.013 · Cited by 236 · see citing works
Siddiqui, M. S., Fuchs, M. A., Idowu, M. O., Luketic, V. A., Boyett, S. L., Sargeant, C., Stravitz, R. T., Puri, P., Matherly, S. C., Sterling, R. K., et al. (2014) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2014.10.008 · Cited by 231 · see citing works
Roubtsova, A., Munkonda, M. N., Awan, Z., Marcinkiewicz, J., Chamberland, A., Lazure, C., Cianflone, K., Seidah, N. G., & Prat, A. (2011) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.110.220988 · Cited by 244 · see citing works
An adipocentric perspective on the development and progression of non-alcoholic fatty liver disease
Lee, E., Korf, H., & Vidal‐Puig, A. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.01.024 · Cited by 228 · see citing works
Intrahepatic Diacylglycerol Content Is Associated With Hepatic Insulin Resistance in Obese Subjects
Magkos, F., Su, X., Bradley, D. P., Fabbrini, E., Conte, C., Eagon, J. C., Varela, J. E., Brunt, E. M., Patterson, B. W., & Klein, S. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.03.003 · Cited by 223 · see citing works
Self-citationPathogenesis of nonalcoholic steatohepatitis
Liu, W., Baker, R. D., Bhatia, T., Zhu, L., & Baker, S. S. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2161-x · Cited by 225 · see citing works
Derwall, M., Malhotra, R. K., Lai, C. S. C., Beppu, Y., Aikawa, E. R., Seehra, J. S., Zapol, W. M., Bloch, K. D., & Yu, P. B. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.242594 · Cited by 224 · see citing works
Metabolic drivers of non-alcoholic fatty liver disease
Bence, K. K., & Birnbaum, M. J. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101143 · Cited by 223 · see citing works
Links Between Ectopic Fat and Vascular Disease in Humans
Lim, S. K., & Meigs, J. B. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303035 · Cited by 218 · see citing works
Central Role of Fatty Liver in the Pathogenesis of Insulin Resistance in Obese Adolescents
D’Adamo, E., Cali, A. M. G., Weiss, R., Santoro, N., Pierpont, B. M., Northrup, V. S., & Caprio, S. (2010) · Diabetes Care · doi:10.2337/dc10-0284 · Cited by 218 · see citing works
Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies
Kosinski, C., & Jornayvaz, F. R. (2017) · Nutrients · doi:10.3390/nu9050517 · Cited by 210 · see citing works
- Authors
- Fabbrini, E., Magkos, F., Mohammed, B. S., Pietka, T., Abumrad, N. A., Patterson, B. W., Okunade, A., & Klein, S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Klein, Samuel
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-09-08
- Volume
- 106
- Issue
- 36
- Pages
- 15430-15435
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2741268
- OpenAlex
- W2077963393
- Semantic Scholar
- 429377a051f8aa5819de277b1869e8f8153ad424
- Cited by
- 972
- References
- 55
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 34 · 2023: 47 · 2022: 50 · 2021: 45 · 2020: 54 · 2019: 55 · 2018: 56 · 2017: 56 · 2016: 60 · 2015: 76 · 2014: 87 · 2013: 89 · 2012: 77
- FWCI
- 49.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- National Institutes of Health (5r01dk060022-19, 5p41rr000954-34, UL1TR000448)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK033301, DK33301, DK37948, DK56341, R01DK037948, DK-60022, R01-DK-060022, P30DK056341)
- National Center for Research Resources (P41-RR000954, RR 00954, UL1RR024992)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- intrahepatic triglyceride, visceral adipose tissue, obesity, insulin sensitivity, VLDL triglyceride secretion, CD36, fatty acid uptake, hepatic insulin resistance, skeletal muscle insulin sensitivity, adipose tissue insulin sensitivity, metabolic complications of obesity
- MeSH terms
- Body Composition, Female, Glucose, Humans, Lipoproteins, VLDL, Liver, Male, Metabolic Diseases, Obesity, Palmitates, Triglycerides, Glucose Clamp Technique, DNA Primers, CD36 Antigens, Reverse Transcriptase Polymerase Chain Reaction, Intra-Abdominal Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
