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.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
13 of 27 cited sources checked · 6 supported · 2 flagged · 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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)”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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).”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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%.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Griffin, M. E., Marcucci, M. J., Cline, G. W., Bell, K., Barucci, N., Lee, D., Goodyear, L. J., Kraegen, E. W., White, M. F., & Shulman, G. I. (1999) · Diabetes · doi:10.2337/diabetes.48.6.1270 · Cited by 1,267
Self-citationLeptin-Replacement Therapy for Lipodystrophy
Oral, E. A., Simha, V., Ruiz, E., Andewelt, A., Premkumar, A., Snell, P., Wagner, A. J., DePaoli, A. M., Reitman, M. L., Taylor, S. I., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012437 · Cited by 1,247
Self-citationLeptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy
Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S., & Goldstein, J. L. (1999) · Nature · doi:10.1038/43448 · Cited by 1,038
Perseghin, G., Scifo, P., De Cobelli, F., Pagliato, E., Battezzati, A., Arcelloni, C., Vanzulli, A., Testolin, G., Pozza, G., Del Maschio, A., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.8.1600 · Cited by 877
Flagged first, then by citations
Research works printed but not linked: 1
- Szczepaniak, 1999, Am J Physiol, 276, E977
Cited by
Sorted by citations
Items 701–797 of 797
Atypical Forms of Type 2 Diabetes
Simha, V., & Garg, A. (2008) · Humana Press eBooks · doi:10.1007/978-1-60327-043-4_27
Hormone-Sensitive Lipase - New roles in adipose tissue biology
Ström, K. (2008) · Lund University Publications (Lund University)
Type 2 diabetes in obese adolescents: pathophysiology and treatment
Kim, G. J., & Caprio, S. (2015) · Wiley eBooks · doi:10.1002/9781118387658.ch55
Bonet, B., Martín, A. M., Alaves, M., et al. (2005) · Endocrinología y Nutrición · doi:10.1016/s1575-0922(05)71034-2
A leptina e o seu impacto metabólico nas lipodistrofias
Lau, E., Freitas, P., Isabel, O. A., & Carvalho, D. M. (2014) · Revista Portuguesa de Endocrinologia Diabetes e Metabolismo · doi:10.1016/j.rpedm.2014.03.003
REPORT OF CONGENITAL GENERALIZED LIPODYSTROPHY IN CHILDREN'S MEDICAL CENTER, TEHRAN, IRAN
Farahmand, F., Yourdkhani, F., Fallahi, G. H., et al. (2005) · GOVARESH
The Problems of Childhood Obesity and the Metabolic Syndrome
Caprio, S., & Weiss, R. (2007) · Springer eBooks · doi:10.1007/978-0-387-32164-6_9
“tion of lipids in both myocytes and the visceral depot [52, 53].”
BackgroundSutinen, J. (2003) · Työväentutkimus Vuosikirja
Acquired Generalized Lipodystrophy with Severe Insulin Resistant Diabetes Mellitus
Lee, J. M., Sohn, T. S., & Son, H. S. (2006) · The Journal of Korean Diabetes Association · doi:10.4093/jkda.2006.30.6.487
Cholic Acid for Hepatic Steatosis in Patients with Lipodystrophy: A Randomized, 1
Ahmad, Z., Subramanyam, L., Szczepaniak, L. S., Simha, V., Adams, B. V., Garg, A., & Boulevard, H. H. (2013)
Steinberg, G. R., Rush, J. W. E., Dyck, D. J., & Ontario, N. (2003)
infusiondiet are corrected by an acute leptin Hepatic steatosis and plasma dyslipidemia induced by
Huang, W., Dedousis, N., Woods, J. A., Vieira‐Potter, V. J., Valentine, R. J., Wilund, K. R., Antao, N. N., Baynard, T., Takeda, E., Sawada, N., et al. (2015)
Jain, J., Mathur, R., Jha, M., & Yadav, S. (2013)
[Monogenic diabetes in children and young adults].
Horikawa, Y. (2012) · PubMed
Leptin Therapy in Women with Hypothalamic Amenorrhea
Chou, S. H.-H., & Mantzoros, C. S. (2014) · Springer eBooks · doi:10.1007/978-3-319-09915-6_19
“The cause of insulin resistance in these populations may be due to increased triglyceride content in liver and muscle, and administration of leptin has been shown to decrease triglyceride content and improve insulin sensitivity in these organs [ 119 ].”
BackgroundWechselwirkungen zwischen Fettzellen und Gehirn
Machleidt, F., Ott, V., & Lehnert, H. (2013) · Der Diabetologe · doi:10.1007/s11428-013-1061-z
Adipose tissue derived IL-6: Regulation of release and physiological significance.
Clarke, D. K. (2004) · OpenGrey (Institut de l'Information Scientifique et Technique)
Vu, B. G., Schlievert, P. M., Squier, C. A., Yahr, T. L., Horswill, A. R., & Apicella, M. A. (2014) · doi:10.17077/etd.y6n7p4ee
Modern science versus the stigma of
Friedman, M. J. (2004)
Unraveling Novel Leptin-Dependent Signaling Pathways in the Basomedial Hypothalamus.
Villanueva, E. C. (2010) · Deep Blue (University of Michigan)
The role of leptin in the regulation of glucose homeostasis
Levi, J. (2010) · cIRcle (University of British Columbia) · doi:10.14288/1.0071042
“Clinical data also show that leptin therapy in patients with generalized lipodystrophy improves lipid metabolism by reducing fasting TG, total cholesterol levels, and additionally improves hepatic steatosis [93-96].”
BackgroundRodríguez, A. J., Neeman, T. M., Giles, A. G., Mastronardi, C. A., & Paz-Filho, G. (2014)
Delmas‐Beauvieux, M., & Gallis, J. (2005) · Elsevier eBooks · doi:10.1016/b978-012564370-2/50123-9
Congenital Generalized Lipodystrophy
Chen, H. (2016) · Springer eBooks · doi:10.1007/978-1-4614-6430-3_51-2
Gogga, P., & Karbowska, J. (2011)
METRELEPTINA: TRATAMIENTO PARA LAS COMPLICACIONES METABÓLICAS DE LA LIPODISTROFIA GENERALIZADA.
Lima-Martínez, M. M. (2016) · Actualidad Contable FACES
Kiràly, M. A. (2008) · TSpace (University of Toronto)
Molina, P. E. (2016) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13219
“…of balanced adipose tissue lipolysis and lipogenesis is supported by reports of hepatic steatosis in leptin-deficient lipodystrophic patients (Petersen et al., 2002) and in subjects with mutations of perilipin-1 (Agarwal and Garg, 2006), a critical protein involved in both pro- and…”
Avaliação da sensibilidade à insulina em pacientes com lúpus eritematoso sistêmico
Miyake, C. N. H. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.5.2016.tde-08092016-100644
Forkhead genes in adipocytes and podocytes
Nilsson, D. (2016) · Gothenburg University Publications Electronic Archive (Gothenburg University) · Cited by 1
Late-Breaking Clinical Trial Report
Chan, J. L., Lutz, K., Cochran, E. K., Huang, W., Peters, Y., Weyer, C., & Görden, P. (2011)
Self-citationa Leptin regulation of inflammatory responses in human gingival fibroblasts
Williams, R. C. (2015)
The metabolic effects of leptin therapy and glucagon suppression therapy in mouse models of diabetes
Neumann, U. H. (2017) · cIRcle (University of British Columbia) · doi:10.14288/1.0348695
“leptin levels, also exhibited hyperglycemia, hyperinsulinemia and insulin resistance, which were corrected by leptin therapy [227-229].”
BackgroundRole of heme oxygenase in cardiomyopathy in obese Zucker fatty rats
Tiwari, S. (2016) · HARVEST (University of Saskatchewan)
Berardinelli’s Syndrome- Anaesthetic Considerations
Associate Professor, G. G., & Nitin, D. G. V. (2019) · Journal of Medical Science And clinical Research · doi:10.18535/jmscr/v7i2.167
Obesity in the Pathophysiology of Diabetes
Paniagua, J. A., & Vidal‐Puig, A. (2019) · Springer eBooks · doi:10.1007/978-3-030-11815-0_13
Huesing, C. (2020) · Louisiana State University · doi:10.31390/gradschool_dissertations.5336
Löfberg, I. E. (2020) · Jyväskylä University Digital Archive (University of Jyväskylä)
Schaarschmidt, W. (2010) · Qucosa (Saxon State and University Library Dresden)
Impacto metabólico e ósseo da dieta hiperproteica em ratas submetidas à restrição calórica
Romano, B. C. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2021.tde-08092021-114856
Lipodistrofia tipo Köbberling, una enfermedad subdiagnosticada
Guillén, D. C., Guillén, A. C., & Barrantes, J. R. C. (2021) · Revista de la Facultad de Medicina de la Universidad de lberoamérica · doi:10.54376/rcmui.v3i2.64
Ectopic Fat and the Metabolic Syndrome
Toledo, F. G. S., & Kelley, D. E. (2007) · Springer eBooks · doi:10.1007/978-0-387-32164-6_7
“This notion is supported by transgenic animal models that have had adipose tissue development inhibited, which results in the phenotypes of ectopic fat and diabetes [70–72].”
BackgroundThe life of a Patient without Adipose Tissue: From Adipocyte Dysfunction to Metabolic Complications
IJDDA, S., Lafqih, M. B., Rafi, S., et al. (2022) · Scholars Journal of Medical Case Reports · doi:10.36347/sjmcr.2022.v10i04.016
Faculty Opinions recommendation of Regulation of hepatic glucose metabolism in health and disease.
Aguilar-Salinas, C. A. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.727825142.793558322
Münzberg, H. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736006202.793574555
Alves, E. S. (2023) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2023.tde-17102023-093636
Chen, L., Zhang, M., Xu, J., & Yang, J. (2024) · Research Square · doi:10.21203/rs.3.rs-3856420/v1
Nassar, W., El‐Ansary, M., Fathy, A., Nassar, M., & Nassar, O. (2023) · Diabetes & its Complications · doi:10.33425/2639-9326.1107
“…withdrawal of glucose lowering agents, following the procedures of bariatric surgery, even in individuals of long-standing type 2 diabetes [31,32], along with rapid reversibility of hepatic insulin resistance [33], may suggest that the nature of the disease is a defect of a concentration…”
BackgroundRamirez‐Cisneros, A., Stefanakis, K., & Mantzoros, C. S. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16194
“39 Lawler et al. further demonstrated that moving from a leptin-deficient to a leptin-replete state increased lipolysis, thereby providing more substrates for fatty acid oxidation.”
Origins and consequences of altered metabolic processes in obese pregnant women
Barr, S. M. (2013) · ERA
Berlanga, A., Guiu‐Jurado, E., Porras, J. A., Aragonès, G., & Auguet, T. (2015) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/j.arteri.2015.03.003 · Cited by 1
Pathophysiology of Insulin Resistance: Implications for Prevention
Ali, S., & Fonseca, V. A. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3314-9_3
Puberty, Insulin Resistance, and Type 2 Diabetes
Goran, M. I., & Sothern, M. S. (2016) · CRC Press eBooks · doi:10.1201/9781420026634-15
The relationship between glycemic intake and insulin resistance in older women
O’Sullivan, T. A. (2008)
Lipodystrophy: The experiment of nature to study leptin
Ahima, R. S., & Jackson, M. B. (2006) · Springer eBooks · doi:10.1007/978-0-387-31416-7_12
Biological Clock Control of Glucose Metabolism
Ruiter, M., Buijs, R. M., & Kalsbeek, A. (2006) · Springer eBooks · doi:10.1007/0-387-23692-9_5
Congenital Generalized Lipodystrophy
Jafri, N., & Zaidi, Z. (2012) · Springer eBooks · doi:10.1007/978-1-4614-1037-9_51
[Clinical pictures of ischemic colitis].
Yamashiro, M., Kanazawa, K., Nakayama, N., Hashimoto, H., & KAGAMI, H. (1976) · PubMed
Other Acquired Disorders of Subcutaneous Fat
Chen, A. Y. ‐., & Garg, A. (2016) · doi:10.1002/9781118441213.rtd0101
Chai, B. K., Murugan, D. D., Rais, M. M., Alshagga, M. A., & Mohankumar, S. K. (2022) · Mediterranean Journal of Nutrition and Metabolism · doi:10.3233/mnm-211562
(2018) · Wiley eBooks · doi:10.1002/9781118829875.refs
Garg, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-812535-9.00002-9
Syndromes of Extreme Insulin Resistance
Grunberger, G., Myneni, A., & Alfonso, B. (2017) · Springer eBooks · doi:10.1007/978-3-319-18741-9_17
Syndromes of Extreme Insulin Resistance
Grunberger, G., & Myneni, A. (2015) · Springer eBooks · doi:10.1007/978-3-319-20797-1_17-1
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2017) · Springer eBooks · doi:10.1007/978-3-319-12125-3_24-2
(2005) · Wiley eBooks · doi:10.1002/9780470774663.refs
The Liver and Insulin Resistance: The Important Convergence of Endocrinology and Hepatology
Chang, C., Whitt, K. N., Liu, Z., & Caldwell, S. H. (2019) · Contemporary Endocrinology · doi:10.1007/978-3-030-25057-7_13
Lewis, G. F. (2003) · Current Opinion in Lipidology · doi:10.1097/00041433-200302000-00015
Congenital Generalized Lipodystrophy
Chen, H. (2017) · Springer eBooks · doi:10.1007/978-1-4939-2401-1_51
The subtleties of insulin treatment in patients with lipodystrophy
Şimşir, İ. Y., Soyaltın, U. E., Çetinkalp, Ş., & Akıncı, B. (2023) · Ege Tıp Dergisi · doi:10.19161/etd.1262624
Therapies in Disorders of Lipid Metabolism and Obesity
Akuffo Quarde, M. D. (2023) · Wiley eBooks · doi:10.1002/9781119863564.ch7
Syndromes of severe insulin resistance: lessons from nature
Krentz, A. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91707-0.00005-x
Non‐Inflammatory Disorders of Subcutaneous Fat
Lee, G. L., Garg, A., & Chen, A. Y. ‐. (2024) · doi:10.1002/9781119709268.rook098
Leptin-related disorders of the nervous system
Saez-Calveras, N., Ishii, M., Elmquist, J. K., & Williams, K. W. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19041-4.00027-3
The Lipodystrophy Syndromes: Clinical Features and Treatments
Mattingly, M., Valencia, A., Cochran, E. K., Brown, R. J., & Görden, P. (2018) · American Diabetes Association eBooks · doi:10.2337/9781580406666.ch03
Neuronal Regulation of Thermogenesis and Energy Expenditure in Metabolic Syndrome
Kumar, S., Gawli, C., & Patil, C. R. (2024) · Advances in biochemistry in health and disease · doi:10.1007/978-3-031-75686-3_16
Metreleptin In SHORT Syndrome With Uncontrolled Diabetes
Korakas, E., Kountouri, A., Ikonomidis, I., Georgiou, I. A., Akıncı, B., & Lambadiari, V. (2025) · JCEM Case Reports · doi:10.1210/jcemcr/luaf218
Liu, X., Huang, L., Wu, Q., Chen, Y., Chen, X., Chen, H., Gao, J., & Xiao, Q. (2022) · Figshare · doi:10.6084/m9.figshare.19753152
Lefebvre, F. A., Paquette, M., & Baass, A. W. (2026) · Journal of clinical lipidology · doi:10.1016/j.jacl.2026.03.020
Implication des neurones exprimant NUCB2/nesfatine-1 dans la régulation de l'homéostasie énergétique
Bonnet, M. S. (2013) · theses.fr (ABES) · doi:10.70675/82840557z70b7z4214zbe5azca1e4f81d53a
Implication of mitochondria endoplasmic-reticulum interactions in the control of hepatic metabolism
Theurey, P. (2015) · theses.fr (ABES) · doi:10.70675/c827066dz5c76z4f0azb465z409dc90bb0e5
Gfi1 : a new target for diabetes therapy
Napolitano, T. (2017) · theses.fr (ABES) · doi:10.70675/aaf52a4az6ce1z446czae57z0d918d5706d5
Homéostasie des céramides et hépatopathies métaboliques
Régnier, M. (2018) · theses.fr (ABES) · doi:10.70675/2fb92711z373cz4b27z8082z7aa3f8930e63
Rôle de LECT2 dans les maladies stéatosiques non alcooliques du foie
Pham, S. (2020) · theses.fr (ABES) · doi:10.70675/3693bfe6z9d91z4045za9a9zc37497dc9c1b
Diabetes in Syndromes of Severe Insulin Resistance
Brown, R. J., & Lightbourne, M. (2026) · Contemporary Endocrinology · doi:10.1007/978-3-032-17036-1_12
Cytokines and insulin sensitivity
Khan, F., Akhtar, S., & Kumar, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33590-7.00008-3
Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system
Hall, J. E., Omoto, A. C. M., do Carmo, J. M., da Silva, A. A., Mouton, A. J., Wang, Z., & Hall, M. E. (2026) · Clinical Science · doi:10.1042/cs20250039
Nagati, V., Tenugu, S., Salazar, M., & Tripathi, M. K. (2026) · Drug Discovery Today · doi:10.1016/j.drudis.2026.104788
Sommer, N., Roumane, A., Tiwari, M., Han, W., Heisler, L. K., Mcilroy, G. D., & Rochford, J. J. (2026) · Gene Therapy · doi:10.1038/s41434-026-00646-w
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 ›
Are you an author, or do you see a problem with this page? Request a review
