The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index; 2 of the 29 sources its claims cite were checked for support.
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.
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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.
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Claims the paper makes
37 Own result · 15 Not checked yet · 13 Own interpretation · 9 Own method · 1 Supported so far
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In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Discussion
What the sources say
- Not checked yetcites [1] source
- Not checked yetcites [2] source
- Supportedcites [3] source
The Discussion reports a strong relationship between intra-abdominal fat (VAT) and liver fat content (IHTG). It also identifies intra-abdominal fat as a determinant of liver fat content. These passages support the VAT–IHTG correlation for which this source is cited. (LLM, conf=0.90)
- Supportedcites [4] source
The citation to this paper is attached to the relationship between increased visceral adipose tissue (VAT) and metabolic disease, not to the proposed IHTG explanation, which has separate citations. In “Body Fat Distribution and Metabolic Complications,” the paper reports that metabolic abnormalities were more closely related to excess visceral adipose tissue than to obesity per se. (LLM, conf=0.93)
- Not checked yetcites (8)(9)(10)
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- Rests on an assumption: A causal link between VAT and metabolic dysfunction has not been demonstrated in humans.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“VAT was not a predictor of any of the dependent variables.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Predictors of Insulin Sensitivity and VLDL-TG Kinetics.
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In the paper
“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)”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Muscle and Adipose Tissue Regulation of Fatty Acid Trafficking.
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In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > VLDL-TG Kinetics.
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In the paper
“However, VLDL-TG secretion rate was not different in subjects with low or high VAT volume, when matched on IHTG content (Fig. 2 A).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > VLDL-TG Kinetics.
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In the paper
“Plasma insulin concentration was inversely correlated with adipose tissue CD36 expression (r ϭ 0.56, P Ͻ 0.01)”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Muscle and Adipose Tissue Regulation of Fatty Acid Trafficking.
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In the paper
“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.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Muscle and Adipose Tissue Regulation of Fatty Acid Trafficking.
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In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Muscle and Adipose Tissue Regulation of Fatty Acid Trafficking.
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- It may state two separate claims as one. 10
- Probably not a substantial claim. 9
- The quote only partly states this claim. 7
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Muscle and Adipose Tissue Regulation of Fatty Acid Trafficking.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > ACKNOWLEDGMENTS.
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- Also stated in: § ACKNOWLEDGMENTS. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > ACKNOWLEDGMENTS.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
- Also stated in: § ACKNOWLEDGMENTS. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > ACKNOWLEDGMENTS.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
- Also stated in: § ACKNOWLEDGMENTS. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > ACKNOWLEDGMENTS.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
- Also stated in: § ACKNOWLEDGMENTS. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > ACKNOWLEDGMENTS.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
- Also stated in: § ACKNOWLEDGMENTS. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > ACKNOWLEDGMENTS.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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The quote only partly states this claim.
- Also stated in: § ACKNOWLEDGMENTS. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > ACKNOWLEDGMENTS.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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The quote only partly states this claim.
- Also stated in: § ACKNOWLEDGMENTS. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > ACKNOWLEDGMENTS.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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The quote only partly states this claim.
- Also stated in: § ACKNOWLEDGMENTS. · plain
In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Discussion
What the sources say
- Not checked yetcites [25] source
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In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Body Composition.
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In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: The mechanism(s) responsible for the interrelationship among IHTG content, insulin resistance, and hypertriglyceridemia is not known.
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In the paper
“Adiponectin administration decreases IHTG (35), increases hepatic insulin sensitivity (36), and reverses obesity-related skeletal muscle insulin resistance (37).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
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In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Discussion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- 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
In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Discussion
What the sources say
- Not checked yetcites [11] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: The mechanism(s) responsible for the interrelationship among IHTG content, insulin resistance, and hypertriglyceridemia is not known.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, increased IHTG is an independent indicator of multiorgan insulin resistance and increased hepatic secretion of VLDL-TG.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Subjects.
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In the paper
“We did not have knowledge of any outcome measures when the matches were performed.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Subjects.
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In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Calculations.
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In the paper
“Subjects within groups were matched on age, sex, BMI, and percentage of body fat.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Subjects.
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In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Statistical Analyses.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Subjects.
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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?
In the citing paper
“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]
Citations
Cites
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621
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
Abdominal obesity and metabolic syndrome
Després, J.-P., & Lemieux, I. (2006) · Nature · doi:10.1038/nature05488 · Cited by 4,354
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
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
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
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
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
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
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
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
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
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
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
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
Self-citation
Metadata
- 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 › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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.
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