The DOI matches its Crossref record; 32 of the 33 references it cites were found in a registry or an index, and 1 are not checked yet; 13 of the 27 sources its claims cite were checked for support.
Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy
Open accessAbstract
Lipodystrophy is a rare disorder that is characterized by selective loss of subcutaneous and visceral fat and is associated with hypertriglyceridemia, hepatomegaly, and disordered glucose metabolism. It has recently been shown that chronic leptin treatment ameliorates these abnormalities. Here we show that chronic leptin treatment improves insulin-stimulated hepatic and peripheral glucose metabolism in severely insulin-resistant lipodystrophic patients. This improvement in insulin action was associated with a marked reduction in hepatic and muscle triglyceride content. These data suggest that leptin may represent an important new therapy to reverse the severe hepatic and muscle insulin resistance and associated hepatic steatosis in patients with lipodystrophy.
Verified 2026-10-10 · 1 reference not checked yet
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In three patients with severe generalized lipodystrophy, chronic recombinant leptin treatment improved insulin-stimulated hepatic and peripheral glucose metabolism and reduced hepatic and muscle triglyceride content. These changes suggest leptin may reverse severe insulin resistance and hepatic steatosis in lipodystrophy.
Key findings
- Before leptin, lipodystrophic patients had severe insulin resistance: glucose infusion rate was 1.2 ± 0.2 vs. 12.7 ± 0.9 mg/kg/min in controls (P < 0.0001), insulin suppression of glucose production was 40% ± 6% vs. 92% ± 7% (P = 0.0004), and fasting glucose production was 3.6 ± 0.8 vs. 1.9 ± 0.1 mg/kg/min (P = 0.019).
- After leptin, glucose infusion rate increased approximately fourfold to 5.4 ± 0.9 mg/kg/min (P = 0.04), insulin suppression of glucose production improved to 82% ± 5% (P < 0.05), and whole-body insulin-stimulated glucose metabolism was 6.1 ± 1.0 vs. 3.5 ± 0.3 mg/kg/min before treatment (P = 0.08).
- Leptin reduced hepatic triglyceride content by 86% ± 8% (P = 0.008) and muscle triglyceride content by 33% ± 3% (P = 0.006); muscle total fatty acyl CoA concentrations decreased by approximately 30%.
- Group mean fasting plasma glucose fell from 234 ± 14 to 122 ± 21 mg/dl (P < 0.05 vs. before treatment), and triglycerides fell from 5851 ± 5079 to 1134 ± 523 mg/dl in Table 1.
Methods
- Three patients with severe generalized lipodystrophy and diabetes (fasting leptin < 4 ng/ml) were studied before and after leptin treatment for 3 months, with patient NIH-1 treated for an additional 5 months; six healthy nonsmoking women of similar age, weight, and BMI served as controls.
- Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp with [6,6-2H2]glucose turnover; lipolysis by [2H5]glycerol turnover; liver and muscle triglyceride by 1H NMR; body fat by DEXA; muscle fatty acyl CoA by biopsy in patient NIH-6; and energy intake/expenditure by monitored diet and indirect calorimetry.
- Differences between controls and lipodystrophic subjects were assessed by Student t tests, and before- vs. after-leptin differences by paired Student t tests; data are mean ± SEM.
Limitations
- The paper does not include a formal limitations section. Evident from the text: the study is very small (3 lipodystrophic patients), open-label, and uses a before-after design without a placebo control.
- Treatment duration differed across patients (3 months for all, 8 months for NIH-1), and some measurements were made in only one patient (energy intake and muscle fatty acyl CoA in NIH-6).
- The paper states that a lipolytic effect of leptin on tissues “cannot be ruled out”; it also reports non-significant changes in glycerol turnover (P = 0.23) and energy expenditure (P = 0.08), so the mechanism is not fully established.
Model-written summary. Check it against the paper before relying on it.
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Verification
Claims the paper makes
18 Own result · 6 Own interpretation · 4 Supported · 4 Partly supported · 4 No full text of the sources · 2 Not supported · 1 No basis given · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“At the time of the postleptin treatment study, all patients had their antidiabetic medication discontinued (5).”
What the sources say
- Disputedcites [5] sourceExperimental — accuracy not yet measured
Table 1 (Patient No.; page unavailable in our copy) shows that patients 3, 7, and 8 were still receiving antidiabetic medication at four months; patient 9 had none to discontinue. The Study Design and Changes in Metabolic Control sections say treatments were tapered or discontinued as needed, not discontinued for all patients. (LLM, conf=0.95)
Checked by a reasoning model — may be wrong.
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.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Energy expenditure was assessed by indirect calorimetry in all patients before and after leptin treatment and was found to be slightly, but not significantly, lower in all patients after leptin treatment (1,660 ± 108 kcal/day before treatment versus 1,403 ± 62 kcal/day after treatment, P = 0.08).”
- Also stated in: another passage · hedged
“In contrast, we found that leptin treatment tended to cause a decrease in energy expenditure, which is consistent with the observations in the entire set of lipodystrophic patients (5).”
What the sources say
- Disputedcites [5] sourceExperimental — accuracy not yet measured
In “Changes in Energy Balance” (page not provided), the paper reports a decrease in resting metabolic rate in all nine patients, but gives different values and finds it statistically significant: 1,920 ± 150 to 1,580 ± 80 kcal/day (P = 0.003). The cited claim instead gives 1,660 ± 108 to 1,403 ± 62 kcal/day and calls the decrease nonsignificant (P = 0.08). (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
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.
- Also stated in: another passage · hedged
Every source the paper cites for this claim was checked and supports it.
In the paper
“it is likely that a fatty acid-derived intermediate, rather than intramyocellular triglyceride, is responsible for mediating the insulin resistance (23).”
What the sources say
- Supportedcites [23] source
In “A unifying hypothesis for common forms of human insulin resistance” (page not provided), the paper says that triglycerides accumulate but intracellular fatty acid metabolites are “probably more importantly” involved in insulin-signaling defects and insulin resistance. This supports the citing sentence’s qualified comparison. (LLM, conf=0.93)
hedgedconditional- 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.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The improved glycemic control could be attributed to a marked increase in their insulin responsiveness, as reflected by an almost fourfold increase in the rate of glucose infusion required to maintain euglycemia during the clamp”
What the sources say
- Partly supportedcites [5] sourceExperimental — accuracy not yet measured
The Changes in Metabolic Control section reports improved glycemic control and insulin sensitivity after leptin therapy. But the Procedures section describes an insulin-tolerance test, not a euglycemic clamp; the reported glucose-disappearance constant rose from 0.007 to 0.017, not an almost fourfold increase in a glucose-infusion rate. No page numbers are available in our copy. (LLM, conf=0.88)
hedgedconditional- 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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“These data support the hypothesis that a similar mechanism for insulin resistance might occur in patients with severe lipodystrophy and more common forms of insulin resistance associated with obesity and type 2 diabetes (23).”
What the sources say
- Supportedcites [23] source
The section “A unifying hypothesis for common forms of human insulin resistance” explicitly proposes a shared mechanism for insulin resistance in lipodystrophy, obesity, and type 2 diabetes. It presents this as a hypothesis, matching the citing sentence’s uncertainty. (LLM, conf=0.94)
hedgedconditional- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Previous studies by our group (9, 17-20) and others (7, 21, 22) have demonstrated a strong relationship between triglyceride content in liver and muscle and insulin resistance in these tissues.”
What the sources say
- Supportedcites [9] source
The Discussion (page not available) reports that improved insulin responsiveness was associated with reduced hepatic triglyceride content, and the References list prior studies linking muscle triglyceride or lipid content with insulin resistance. The paper also notes that muscle triglyceride did not fall despite improved muscle insulin sensitivity in its own trial; this does not negate the cited claim about relationships demonstrated in previous studies. (LLM, conf=0.83)
- Could not verifycites [17] sourceExperimental — accuracy not yet measured
The Introduction and Discussion report that elevated plasma free fatty acids induce insulin resistance in human skeletal muscle. They do not report a relationship between triglyceride content in liver or muscle and insulin resistance in those tissues (searched: triglyceride content, intramuscular triglyceride, liver triglyceride). (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [18] source
- Not checked — no full text of the sourcecites [19] source
- Not checked — no full text of the sourcecites [20] source
- Not checked — no full text of the sourcecites [7] Szczepaniak, 1999, Am J Physiol source
- Not checked — no full text of the sourcecites [21] source
- Partly supportedcites [22] sourceExperimental — accuracy not yet measured
The Discussion reports a strong correlation between liver fat percentage and hepatic insulin sensitivity, supporting the liver portion of the claim. Our copy does not report a relationship between muscle triglyceride content and muscle insulin resistance; its mention of skeletal-muscle insulin resistance does not establish that relationship. The indexed passages provide section labels but no page numbers. (LLM, conf=0.88)
boostedcorrelational- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Energy intake was monitored in patient NIH-6, and leptin treatment caused an approximately 50% reduction in energy intake, from 2,017 kcal/day before treatment to 962 kcal/day after 3 months of treatment.”
- Also stated in: another passage · hedged
“Furthermore, when energy intake was carefully monitored in an inpatient setting, we found an approximately 50% reduction in the caloric intake in one patient following leptin therapy, which is similar to the self-reported observations by Arioglu Oral et al. (5) in the entire set of nine lipodystrophic patients and by Farooqi et al. (27) in a child with congenital leptin deficiency who was treated”
What the sources say
- Partly supportedcites [5] sourceExperimental — accuracy not yet measured
The Changes in Energy Balance section reports that mean self-reported intake fell during leptin therapy, from 2,680 to 1,600 kcal/day after four months. It does not report the claimed 2,017-to-962 kcal/day change for patient NIH-6 after three months; the Procedures section says food intake was reported at baseline and four months. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [27] source
plaindirectSingle case- 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.
- Also stated in: another passage · hedged
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“While there were no appreciable differences in intramyocellular triglyceride content between the control and lipodystrophic patients”
plain- 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.
- 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
“Consistent with the former possibility, all patients reported a marked reduction in appetite following leptin treatment.”
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.
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
“The lipodystrophic patients were severely insulin resistant, as reflected by the very low rates of glucose infusion required to maintain euglycemia during the hyperinsulinemic-euglycemic clamp (lipodystrophic, 1.2 ± 0.2 mg/kg/min versus control, 12.7 ± 0.9 mg/kg/min; P < 0.0001)”
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.
- Probably not a substantial claim. 6
- It may state two separate claims as one. 10
- The quote only partly states this claim. 2
Every source the paper cites for this claim was checked and supports it.
In the paper
“More recently, Arioglu Oral et al. found that human recombinant leptin therapy reduced hyperglycemia and hypertriglyceridemia and increased the rate of glucose disappearance during an intravenous insulin tolerance test in nine lipodystrophic patients (5).”
What the sources say
- Supportedcites [5] source
The Abstract reports that nine patients with lipodystrophy received recombinant human leptin and that treatment improved glycemic control and reduced triglycerides. Changes in Metabolic Control reports an increased rate of glucose disappearance during the insulin-tolerance test; Figure 2 specifies intravenous insulin administration. Page numbers are not supplied in the passages. (LLM, conf=0.94)
plaindirectn = 9- 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. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, fatty acids have been shown to increase hepatic gluconeogenesis (25, 26).”
What the sources say
- Supportedcites [25] source
The Introduction reports that gluconeogenesis rose when free fatty acids rebounded in healthy, nonobese subjects fasting for 24 hours. Table 3 in “FFA and GNG” also shows a rise in the measured gluconeogenesis rate during that rebound. The claim is a fair broad paraphrase of this finding. (LLM, conf=0.91)
- Supportedcites [26] source
The Discussion (p. 5) states that plasma free-fatty-acid elevation has been shown to increase gluconeogenesis in humans. The paper’s conclusion (p. 6) narrows its own finding: high FFA concentrations increased gluconeogenesis’s contribution to glucose production in healthy humans, while total endogenous glucose production remained unchanged. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, recent studies by our group have challenged this hypothesis and found evidence to suggest that intracellular accumulation of fatty acid-derived metabolites, such as fatty acyl CoA's, leads to activation of protein kinase Cθ , resulting in activation of a serine/threonine cascade that leads to increased serine phosphorylation of insulin receptor substrate-1 (IRS-1). IRS-1 in”
What the sources say
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
The Discussion proposes fatty acyl CoA accumulation, activation of a serine kinase (possibly PKCθ), IRS-1 serine phosphorylation, and reduced IRS-1-associated PI 3-kinase activity as a hypothesis. It does not establish the full proposed cascade or show that it reduces IRS-1 tyrosine phosphorylation or GLUT4; the Discussion presents GLUT4 effects as possibilities. Page numbers are unavailable in our copy. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [18] source
hedgeddirect- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
- Partly supported
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
“There was a marked reduction in the fasting plasma glucose concentration in patients NIH-3 and NIH-6 after 3 months of leptin treatment and in NIH-1 after 8 months of leptin treatment (Table 1).”
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.
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
“Prior to leptin treatment, all patients had poorly controlled diabetes (as reflected by fasting hyperglycemia and increased glycosylated hemoglobin), and hyperlipidemia (Table 1).”
plainn = 3- 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 quote only partly states this claim.
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
“The fasting respiratory quotient was also unaffected by leptin treatment (0.85 ± 0.06 before treatment versus 0.90 ± 0.03 after treatment; P = 0.1).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“These alterations were associated with severe hepatic steatosis in all of the patients: NIH-1, 48% liver triglyceride content, NIH-3, 4.6% liver triglyceride content, and NIH-6, 26% liver triglyceride content. In the control subjects, liver triglyceride content was less than 1%.”
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.
It may state two separate claims as one.
In the paper
“there was a tendency for energy expenditure to be higher in the lipodystrophic subjects (lipodystrophic, 1,660 ± 108 kcal/day versus control subjects, 1,368 ± 96 kcal/day; P = 0.10)”
What the sources say
- Not checked — no full text of the sourcecites [16] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Shimomura et al. have demonstrated that leptin treatment reversed insulin resistance in a fat-specific aP2-SREBP-1c knockout mouse model of congenital generalized lipodystrophy (4).”
What the sources say
- Not checked — no full text of the sourcecites [4] source
boosteddirect- 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.
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
“Leptin treatment may have caused this reduction in hepatocyte and myocellular triglyceride content through decreased food intake and/or promotion of increased energy expenditure.”
hedgedconditional- 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.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Lipodystrophy is a rare disorder that is characterized by selective loss of subcutaneous and visceral fat. This disease is associated with hypertriglyceridemia, hepatic steatosis, and severe insulin resistance that often results in diabetes (1-3).”
What the sources say
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.
Probably not a substantial claim. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Taken together, these data suggest that intrahepatic and intramyocellular lipid lowering effects of leptin were mediated mostly by a reduction in energy intake, as opposed to a leptininduced increase in energy expenditure, although a lipolytic effect of leptin on these tissues cannot be ruled out (4, 28).”
What the sources say
hedgedconditionalSingle case- 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.
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
“Chronic leptin treatment caused a marked improvement in whole-body insulin-stimulated glucose metabolism, which could be attributed to both improved insulin sensitivity in the liver (as reflected by improved insulin suppression of glucose production) and in the muscle (as reflected by an increase in insulinstimulated peripheral glucose uptake).”
hedgeddirect- 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.
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
“These data suggest that leptin may represent an important new therapy to reverse the severe hepatic and muscle insulin resistance and associated hepatic steatosis in patients with lipodystrophy.”
- Also stated in: another passage · hedged
“These data suggest that leptin therapy may represent an important new therapy to treat insulin resistance, hepatic steatosis, and the associated diabetes in patients with severe lipodystrophy.”
hedgedconditional- 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.
- Also stated in: another passage · hedged
The paper relies on this without support.
The observed improvements after leptin treatment are attributable to leptin rather than to other concurrent changes or factors.
“At the time of the postleptin treatment study, all patients had their antidiabetic medication discontinued (5).”
The paper relies on this without support.
The three studied lipodystrophic patients are representative of patients with severe lipodystrophy.
“Three patients with severe, generalized lipodystrophy (fasting leptin concentration less than 4 ng/ml) associated with diabetes were studied.”
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
“The unifying model of diacylglycerol-induced insulin resistance accounts for the insulin resistance seen in obesity, and in other disorders such as congenital and acquired lipodystrophy,82 in young lean offspring of patients with type 2 diabetes mellitus, and with increase in age.66”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [82]
In the citing paper
“NAFLD is strongly linked to hepatic insulin resistance”
From The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome (2007) · cites this paper as [20]
In the citing paper
“recent studies have demonstrated that NAFLD-induced hepatic insulin resistance is a major factor responsible for the transition from normoglycemia to fasting hyperglycemia and T2DM (18–23).”
From The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome (2007) · cites this paper as [20]
In the citing paper
“Several studies have shown a strong relationship among nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes mellitus.1–3”
From Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease (2010) · cites this paper as [1]
In the citing paper
“There is now strong evidence that nonalcoholic fatty liver disease has an important role in causing hepatic insulin resistance.1–3,23–27”
From Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease (2010) · cites this paper as [1]
In the citing paper
“An alternate hypothesis is that the development of hepatic steatosis per se causes hepatic insulin resistance.”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [8]
In the citing paper
“There is increasing evidence for a causal relationship between hepatic steatosis and hepatic insulin resistance both in rodent models with hepatic steatosis and in patients with nonalcoholic fatty liver disease (4, 18-25).”
From Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men (2006) · cites this paper as [18]
In the citing paper
“leptin therapy has been examined in several clinical trials in patients with lipodystrophy and these have demonstrated significant improvements in glycemia, dyslipidemia and hepatic steatosis (89, 90, 139, 142).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [142]
In the citing paper
“These parameters have been validated previously by the hyperinsulinemic-euglycemic clamp technique”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [11]
In the citing paper
“showing that r-metHuLeptin increases insulin-stimulated peripheral glucose uptake and increases insulin suppression of hepatic glucose output (11).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [11]
In the citing paper
“Moreover, leptin dramatically improves insulin sensitivity in human lipodystrophy and in lipodystrophic mouse models which are characterized by low serum leptin levels and by severe insulin resistance (Oral et al., 2002; Petersen et al., 2002; Shimomura et al., 1999).”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Petersen et al., 2002
Citations
Cites
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751
The metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963) · The Lancet · doi:10.1016/s0140-6736(63)91500-9 · Cited by 5,093
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
Self-citationEffects of Recombinant Leptin Therapy in a Child with Congenital Leptin Deficiency
Farooqi, I. S., Jebb, S. A., Langmack, G., Lawrence, E., Cheetham, C. H., Prentice, A. M., Hughes, I. A., McCamish, M. A., & O'Rahilly, S. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909163411204 · Cited by 1,998
Dresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311
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Self-citationLeptin-Replacement Therapy for Lipodystrophy
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Congenital generalized lipodystrophy
Filho, P. P. F., Val, A. C., Diamante, R., et al. (2004) · Jornal de Pediatria · doi:10.2223/1209 · Cited by 14
Novel factors as therapeutic targets to treat diabetes. Focus on leptin and ghrelin
Gómez, R., Lago, F., Gómez-Reino, J. J., & Gualillo, O. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220902914834 · Cited by 14
“In line with this, other authors also reported improvement in insulin sensitivity after leptin administration in lipodystrophic patients [64-66].”
ResultRole of the Adipocyte in Metabolism and Endocrine Function
Ravussin, É., & Smith, S. R. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00036-6 · Cited by 16
Pathogenesis of Type 2 Diabetes Mellitus
DeFronzo, R. A. (2018) · Endocrinology · doi:10.1007/978-3-319-45015-5_8 · Cited by 14
Hartinger, R., Lederer, E.-M., Schena, E., Lattanzi, G., & Djabali, K. (2023) · Cells · doi:10.3390/cells12101350 · Cited by 14
“Lipodystrophy is characterized by a general or selective loss of subcutaneous and visceral fat and alteration in the body fat compositions [11,12].”
BackgroundFatty liver and chronic inflammation in Chinese adults
Wang, P., Hsieh, C., Psang, L.-C., Cheng, Y., Liou, C., Weng, S., Chen, J., Chen, I., Li, R.-H., & Eng, H. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.04.014 · Cited by 13
From the conceptual basis to the discovery of leptin
Fève, B., & Bastard, J. (2012) · Biochimie · doi:10.1016/j.biochi.2012.06.028 · Cited by 13
Görden, P., Zadeh, E. S., Cochran, E. K., & Brown, R. J. (2012) · Endocrine Practice · doi:10.4158/ep12139.ra · Cited by 13
Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin
da Silva, A. A., Hall, J. E., Moak, S. P., Browning, J. R., Houghton, H. J., Micheloni, G. C., & do Carmo, J. M. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00301.2016 · Cited by 13
Mcilroy, G. D., Mitchell, S. E., Han, W., Delibegović, M., & Rochford, J. J. (2018) · Scientific Reports · doi:10.1038/s41598-018-36078-9 · Cited by 13
Non-Alcoholic Fatty-Liver Disease in Pediatric Populations
Chávez-Tapia, N. C., Sánchez-Ávila, J. F., Vásquez‐Fernández, F., Torres‐Machorro, A., Téllez-Ávila, F. I., & Uribe, M. (2007) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2007.20.10.1059 · Cited by 13
Lipoatrophic Diabetes in an Elderly Woman: Clinical Course and Serum Adipocytokine Concentrations
Iglesias, P., Fidalgo, P. A., Codoceo, R., & Díez, J. J. (2004) · Endocrine Journal · doi:10.1507/endocrj.51.279 · Cited by 13
Brain Insulin and Leptin Signaling in Metabolic Control
Scherer, T., Lehnert, H., & Hallschmid, M. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2012.11.002 · Cited by 11
Role of AMPK in the Regulation of Cellular Energy Metabolism
Ha, J., & Lee, S.-H. (2010) · Journal of Korean Endocrine Society · doi:10.3803/jkes.2010.25.1.9 · Cited by 12
“Adipokine의 일종인 leptin이 말초 조직에서 당 유입을 증가시키는 것으로 최근에 보고되 었다[35,36].”
Perinephric and Epididymal Fat Affect Hepatic Metabolism in Rats
Ben‐Shlomo, S., Einstein, F. H., Zvibel, I., Atias, D., Shlomai, A., Halpern, Z., Barzilai, N., & Fishman, S. (2011) · Obesity · doi:10.1038/oby.2011.261 · Cited by 12
“Indeed, leptin resistance in obese human subjects and diet-induced obese rodents is thought to be a contributing factor in hepatic lipid accumulation (16,20,21).”
BackgroundMay, P., Brémond, P., Sauzet, C., Piccerelle, P., Grimaldi, F., Champion, S., & Villard, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030841 · Cited by 12
“Chronic leptin replacement therapy has been shown to reverse liver and muscle insulin resistance and fasting hyperglycaemia in patients displaying a severe lipodystrophy [47].”
BackgroundLeptin-induced weight loss is not solely mediated by anorexia
Dötsch, J., Meißner, U., & Rascher, W. (2003) · European Journal of Endocrinology · doi:10.1530/eje.0.1480011 · Cited by 12
Aizawa‐Abe, M., Ebihara, K., Ebihara, C., Mashimo, T., Takizawa, A., Tomita, T., Kusakabe, T., Yamamoto, Y., Aotani, D., Yamamoto‐Kataoka, S., et al. (2013) · Physiological Genomics · doi:10.1152/physiolgenomics.00040.2013 · Cited by 12
Valtueña, S., Numeroso, F., Ardigò, D., Pedrazzoni, M., Franzini, L., Piatti, P. M., Monti, L. D., & Zavaroni, I. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01960 · Cited by 12
Gaal, L. F. V., Mertens, I. L., & Abrams, P. J. (2003) · Growth Hormone & IGF Research · doi:10.1016/s1096-6374(03)00046-7 · Cited by 12
“Also, suppression of hepatic glucose production was roughly three times higher after 4 months of therapy [35].”
BackgroundPatogenia de la hepatopatía grasa no alcohólica primaria
Sánchez, D. M. (2005) · Medicina Clínica · doi:10.1157/13074744 · Cited by 12
Leptin Therapy in Patients with Lipodystrophy and Syndromic Insulin Resistance
Brown, R. J., & Görden, P. (2014) · Springer eBooks · doi:10.1007/978-3-319-09915-6_18 · Cited by 12
A Monoclonal Antibody Against Leptin
Mahmoudian, J., Jeddi‐Tehrani, M., Bayat, A. A., Mahmoudi, A. R., Vojgani, Y., Tavangar, B., Hadavi, R., & Zarei, S. (2012) · Hybridoma · doi:10.1089/hyb.2012.0045 · Cited by 12
American College of Endocrinology Pre-Diabetes Consensus Conference: Part Three
Bloomgarden, Z. T. (2008) · Diabetes Care · doi:10.2337/dc08-zb12 · Cited by 13
Benefits of leptin therapy in HIV patients
Sinha, U., Sinharay, K., Sengupta, N., & Mukhopadhyay, P. (2012) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.105583 · Cited by 12
Insulin Resistance in Type 2 Diabetes
Roden, M., Petersen, K. F., & Shulman, G. I. (2024) · Wiley eBooks · doi:10.1002/9781119697473.ch17 · Cited by 14
Advances in the care of lipodystrophies
Shamsudeen, I., & Hegele, R. A. (2021) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000695 · Cited by 11
Third Annual World Congress on the Insulin Resistance Syndrome
Bloomgarden, Z. T. (2006) · Diabetes Care · doi:10.2337/dc06-zb07 · Cited by 11
“” In humans with lipodystrophy, there are low circulating leptin levels, with leptin replacement therapy controlling the insul in-resistant diabetes, leading to normalization of glucose and reduction in liver and muscle fat (13).”
BackgroundKosmiski, L. A., Ringham, B. M., Grunwald, G. K., & Bessesen, D. H. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.28103 · Cited by 11
“This lipotoxicity is likely the major cause of the insulin resistance and diabetes associated with the lipoatrophy syndromes (17, 20, 21).”
BackgroundLightbourne, M., Wolska, A. T., Abel, B. S., Rother, K. I., Walter, M. F., Kushchayeva, Y. S., Auh, S., Shamburek, R. D., Remaley, A. T., Muniyappa, R., et al. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa191 · Cited by 11
Short-term overfeeding increases resting energy expenditure in patients with HIV lipodystrophy
Kosmiski, L. A., Bessesen, D. H., STOTZ, S. A., Koeppe, J. R., & Horton, T. J. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.4.1009 · Cited by 11
Treatment of Obesity and Diabetes in Mice by Transplant of Gut Cells Engineered to Produce Leptin
Oosman, S. N., Lam, A., Harb, G., Unniappan, S., Lam, N. T., Webber, T. D., Bruch, D., Zhang, Q., Korbutt, G. S., & Kieffer, T. J. (2008) · Molecular Therapy · doi:10.1038/mt.2008.62 · Cited by 12
The 6th Annual World Congress on the Insulin Resistance Syndrome
Bloomgarden, Z. T. (2009) · Diabetes Care · doi:10.2337/dc09-zb09 · Cited by 11
Nyström, T., Bratt, G., & Sjöholm, Å. (2002) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.2002.01074.x · Cited by 11
Leptin replacement therapy in the management of lipodystrophy syndromes
Vigouroux, C., Mosbah, H., & Vatier, C. (2024) · Annales d Endocrinologie · doi:10.1016/j.ando.2024.05.022 · Cited by 11
Pathogenesis of Type 2 Diabetes Mellitus
DeFronzo, R. A. (2018) · Endocrinology · doi:10.1007/978-3-319-27317-4_8-1 · Cited by 11
Zouhar, P., Rakipovski, G., Bokhari, M. H., Busby, O., Paulsson, J. F., Conde‐Frieboes, K. W., Fels, J. J., Raun, K., Andersen, B., Cannon, B., et al. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00253.2019 · Cited by 10
Casey, S., Lokan, J., Testro, A., Farquharson, S., Connelly, A., Proietto, J., & Angus, P. (2013) · American Journal of Transplantation · doi:10.1111/ajt.12436 · Cited by 10
“Two previous studies have investigated the effects of leptin replacement on liver fat content in LD patients using MRS and have shown marked decreases in liver F:W within months of commencing leptin therapy (9,10).”
BackgroundMetabolic heterogeneity of obesity: role of adipose tissue
McLaughlin, T. (2012) · International Journal of Obesity Supplements · doi:10.1038/ijosup.2012.3 · Cited by 11
Treatment Options for Lipodystrophy in Children
Mainieri, F., Tagi, V. M., & Chiarelli, F. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.879979 · Cited by 10
“Given the improvements of metreleptin in insulin sensitivity (55, 56), half of the patients obtained the discontinuation of insulin therapy after 1-year administration of metreleptin.”
BackgroundLeptin and Appetite Control in Lipodystrophy
Ahima, R. S., & Osei, S. Y. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1232 · Cited by 10
Circulation Free Leptin in Diabetic Patients and its Correlation to Insulin Level
Mohiti, J., Talebi, F., & Afkhami-Ar, M. (2009) · Pakistan Journal of Biological Sciences · doi:10.3923/pjbs.2009.397.400 · Cited by 10
Non-alcoholic Fatty Liver Disease
Smolle, E., Kessler, S. M., Golob, N., & Haybaeck, J. (2015) · Springer eBooks · doi:10.1007/978-3-319-11251-0_36 · Cited by 10
Alterations of leptin and ghrelin serum concentrations in renal disease: simple epiphenomena?
Dötsch, J., Nüsken, K., Schroth, M. A., Rascher, W., & Meißner, U. (2005) · Pediatric Nephrology · doi:10.1007/s00467-005-1908-7 · Cited by 10
“The application of leptin reduces hepatic fat mass and improves insulin sensitivity in humans suffering from this condition [11, 12].”
BackgroundWang, Y. (2010) · Wiley eBooks · doi:10.1002/9781444323351.ch18 · Cited by 10
Common Pathogenetic Pathways of Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus
Giannopoulos, C., Tzima, I. G., Tentolouris, N., & Vasileiadis, I. (2023) · Current Diabetes Reviews · doi:10.2174/1573399819666230216112032 · Cited by 12
Syndromes of Extreme Insulin Resistance
Grunberger, G., & Alfonso, B. (2009) · Springer eBooks · doi:10.1007/978-0-387-09841-8_17 · Cited by 9
Leptin and Its Emerging Role in Children and Adolescents
Kelesidis, I., & Mantzoros, C. S. (2006) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.15.1 · Cited by 8
Visceral fat does not contribute to metabolic disease in lipodystrophy
Malandrino, N., Reynolds, J. C., Brychta, R. J., Chen, K. Y., Auh, S., Gharib, A. M., Startzell, M. S., Cochran, E. K., & Brown, R. J. (2018) · Obesity Science & Practice · doi:10.1002/osp4.319 · Cited by 8
“Despite adipose tissue deficiency, patients with lipodystrophy show increased rates of lipolysis, possibly due to increased lipolysis in the residual adipose tissue and/or increased intrahepatic or intravascular lipolysis (29,30).”
BackgroundHepatic deficiency of Poldip2 in type 2 diabetes modulates lipid and glucose homeostasis
Jiang, Z., Zhou, J., Li, T., Tian, M., Lü, J., Jia, Y., Wan, G., & Chen, K. (2019) · Metabolism · doi:10.1016/j.metabol.2019.153948 · Cited by 9
Energy balance in congenital generalized lipodystrophy type I
Taleban, S., Carew, H., Dichek, H. L., Deeb, S. S., Hollenback, D., Weigle, D. S., Cummings, D. E., & Brunzell, J. D. (2008) · Metabolism · doi:10.1016/j.metabol.2008.04.008 · Cited by 9
“Studies by Petersen and Oral, who measured basal metabolic rate before and after leptin therapy, reported no change and a mean decrease from 1920 to 1580 kcal/day, respectively [13, 30].”
MethodRole of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose Lowering
Takanashi, M., Taira, Y., Okazaki, S., Takase, S., Kimura, T., Li, C. C., Xu, P., Noda, A., Sakata, I., Kumagai, H., et al. (2017) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.39552 · Cited by 9
Leptin: a novel therapeutic role in lipodystrophy
Savage, D. B., & O’Rahilly, S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200215326 · Cited by 9
Huang, W.-W., Shen, B., Li, X., Zhang, T., & Zhou, X. Q. (2023) · Foods · doi:10.3390/foods12183393 · Cited by 8
“[12] suggest that NAFLD results from an overabundance of triglyceride accumulation in the liver due to an energy surplus, which is consistent with the higher prevalence of NAFLD in obese in‐ dividuals.”
Clinical Guidance for Lipodystrophy Syndromes: From Diagnosis and Work-Up to Treatment
Gilio, D., Foss‐Freitas, M. C., & Oral, E. A. (2025) · Current Diabetes Reports · doi:10.1007/s11892-025-01603-4 · Cited by 13
“Additional benefits include decreased low-density lipoprotein choles - terol (LDL-C), total cholesterol [ 95, 96] and hepatic steatosis within 6–12 months [ 51, 93, 97–99].”
Pathogenesis of NAFLD and NASH
Maher, J. J. (2015) · Springer eBooks · doi:10.1007/978-3-319-20538-0_4 · Cited by 8
Mazidi, M., Gao, H.-K., Li, L., Hui, H., & Ye, Z. (2017) · Surgery · doi:10.1016/j.surg.2016.11.027 · Cited by 8
“Furthermore, another study has reported that as leptin has been shown to influence glucose metabolism through mechanisms assumed to be regulated by both central and peripheral leptin signaling, it is probable that elevated leptin sensitivity causes improvement of glucose metabolism independent of weight loss after RYG…”
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Adipokines in Nonalcoholic Fatty Liver Disease
Baranova, A. V., Birerdinc, A., & Younossi, Z. M. (2014) · Humana Press eBooks · doi:10.1007/978-1-62703-770-9_17 · Cited by 8
Berardinelli–Seip syndrome: highlight of treatment challenge
Ferraria, N., Pedrosa, C., Amaral, D., & Lopes, L. (2013) · BMJ Case Reports · doi:10.1136/bcr-2012-007734 · Cited by 8
“29 They also proved that leptin treatment was able to correct hepatic steatosis and reverse insulin resistance 24 with bene fi ts sustained for at least 12 months of treatment.”
Translational Research of Leptin in Lipodystrophy and Its Related Diseases
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Role of ectopic fat in the pathogenesis of insulin resistance
Kantartzis, K., Totsikas, C., Häring, H., & Stefan, N. (2009) · Clinical Lipidology · doi:10.2217/clp.09.35 · Cited by 7
Pediatric Nonalcoholic Fatty Liver Disease
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Consequences of Dicarbonyl Stress on Skeletal Muscle Proteins in Type 2 Diabetes
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Metreleptin treatment of non-HIV lipodystrophy syndromes
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Zukünftige Angriffspunkte für die Therapie des Typ-2-Diabetes
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Leptin acutely increases hepatic triglyceride secretion in patients with lipodystrophy
Beghini, M., Metz, M., Baumgartner, C., Wolf, P. S., Bastian, M., Hackl, M. T., Baumgartner-Parzer, S. M., Marculescu, R., Krebs, M., Harreiter, J., et al. (2025) · Metabolism · doi:10.1016/j.metabol.2025.156261 · Cited by 7
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Insulin Resistance in NAFLD: Potential Mechanisms and Therapies
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“Meanwhile, increased intrahepatic ectopic lipids may promote hepatic insulin resistance [9].”
BackgroundZheng, P. (2008) · Journal of Chinese Integrative Medicine · doi:10.3736/jcim20080909 · Cited by 6
Genetic Disorders of Insulin Action: Far More than Diabetes
Challis, B., & Semple, R. K. (2013) · Current Obesity Reports · doi:10.1007/s13679-013-0075-6 · Cited by 6
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“Recent studies have shown recombinant leptin to be effective in improving hyperglycemia, dyslipidemia, and hepatic steatosis in patients with lipodystrophies [24-26].”
BackgroundMolecular Determinants of the Cardiometabolic Phenotype
Fuentes, L. D. L., SIMONE, G. D., Arnett, D. K., & Dávila‐Román, V. G. (2010) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/187153010791213119 · Cited by 7
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1H-Magnetresonanzspektroskopie (MRS) der Leber und von Lebermalignomen bei 3,0�Tesla
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Interplay between the immune and skeletal cells in the regulation of inflammatory bone destruction
Suematsu, A., & Takayanagi, H. (2007) · Japanese Journal of Clinical Immunology · doi:10.2177/jsci.30.22 · Cited by 5
Miehle, K., von Schnurbein, J., Faßhauer, M., Stümvoll, M., Borck, G., & Wabitsch, M. (2017) · Medizinische Genetik · doi:10.1007/s11825-017-0162-2 · Cited by 3
Metadata
- Authors
- Petersen, K. F., Oral, E. A., Dufour, S., Befroy, D., Ariyan, C., Yu, C., Cline, G. W., DePaoli, A. M., Taylor, S. I., Gorden, P., & Shulman, G. I.
- Affiliations
- Yale University (US)
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Amgen (United States) (US)
- Corresponding author
- Petersen, Kitt Falk
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2002-05-15
- Volume
- 109
- Issue
- 10
- Pages
- 1345-1350
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC150981
- OpenAlex
- W2164714249
- Cited by
- 800
- References
- 26
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 20 · 2023: 21 · 2022: 23 · 2021: 27 · 2020: 25 · 2019: 29 · 2018: 29 · 2017: 31 · 2016: 38 · 2015: 39 · 2014: 34 · 2013: 45 · 2012: 35
- FWCI
- 26.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- Yale University
- National Institutes of Health (P30 DK)
- National Institute of Diabetes and Digestive and Kidney Diseases (K-23 DK-02347, R01 DK-42930, P30DK045735)
- National Center for Research Resources (M01RR000125)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- leptin, lipodystrophy, insulin resistance, hepatic steatosis, hepatic glucose metabolism, muscle glucose metabolism, triglyceride accumulation, hypertriglyceridemia, hepatomegaly
- MeSH terms
- Adult, Diabetes Mellitus, Type 2, Fatty Liver, Female, Humans, Insulin Resistance, Lipodystrophy, Liver, Hypertriglyceridemia, Leptin
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 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (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.
What counts as a claim ›How we measure confidence ›How we check this ›
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