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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Cites
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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 201–300 of 797
The Metabolic Syndrome in Patients With Severe Mental Illnesses
Toalson, P. A., Ahmed, S., Hardy, T. A., & Kabinoff, G. S. (2004) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.v06n0402 · Cited by 106
Vatner, D. F., Weismann, D., Beddow, S. A., Kumashiro, N., Erion, D. M., Liao, X.-H., Grover, G. J., Webb, P., Phillips, K. J., Weiss, R. E., et al. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00573.2012 · Cited by 110
Role of adipokines in the control of energy metabolism: focus on adiponectin
Lafontan, M., & Viguerie, N. (2006) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2006.08.002 · Cited by 118
Teng, W., Zhao, L., Yang, S., Zhang, C., Liu, M., Luo, J., Jin, J., Zhang, M., Bao, C., Li, D., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.06.023 · Cited by 107
Park, J. Y., Javor, E. D., Cochran, E. K., DePaoli, A. M., & Görden, P. (2007) · Metabolism · doi:10.1016/j.metabol.2006.11.010 · Cited by 103
“We have interpreted the improvement in fasting glucose to be related to improvement in insulin sensitivity as shown by insulin tolerance tests, previously validated by the euglycemic clamp [21].”
MethodLipodystrophies, dyslipidaemias and atherosclerotic cardiovascular disease
Hussain, I., Patni, N., & Garg, A. (2018) · Pathology · doi:10.1016/j.pathol.2018.11.004 · Cited by 105
Cettour-Rose, P., Theander-Carrillo, C., Asensio, C. S., Klein, M., Visser, T. J., Burger, A., Meier, C. A., & Rohner‐Jeanrenaud, F. (2005) · Diabetologia · doi:10.1007/s00125-005-1696-4 · Cited by 104
“Together, these data are in keeping with those of the literature showing that peripheral leptin administration as well as transgenic leptin overexpression are able to correct, at least in part, insulin resistance of human and rodent models of lipodystrophy [43, 50–52].”
ResultCellular and Molecular Mechanisms of Insulin Resistance
Chandrasekaran, P., & Weiskirchen, R. (2024) · Current Tissue Microenvironment Reports · doi:10.1007/s43152-024-00056-3 · Cited by 137
Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes
Toyoshima, Y., Gavrilova, O., Yakar, S., Jou, W., Pack, S., Shyr, Z. A., Wheeler, M. B., & LeRoith, D. (2005) · Endocrinology · doi:10.1210/en.2005-0087 · Cited by 108
“Furthermore, in several clinical trials of leptin treatment, it has been shown that leptin improved the glycemic control, increased insulin sensitivity, and decreased TG levels in patients with lipodystrophy and leptin deficiency (19, 20, 62).”
BackgroundObesity and metabolic disease: is adipose tissue the culprit?
Frayn, K. N. (2005) · Proceedings of The Nutrition Society · doi:10.1079/pns2004403 · Cited by 100
“2004) and leptin administration to patients with lipodystrophy (who are severely insulin resistant and have low levels of leptin) produces a dramatic improvement in their metabolic condition (Oral et al. 2002; Petersen et al. 2002).”
BackgroundBrown, R. J., Valencia, A., Startzell, M. S., Cochran, E. K., Walter, P. J., Garraffo, H. M., Cai, H., Gharib, A. M., Ouwerkerk, R., Courville, A. B., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95476 · Cited by 102
Self-citationKusakabe, T., Tanioka, H., Ebihara, K., Hirata, M., Miyamoto, L., Miyanaga, F., Hige, H., Aotani, D., Fujisawa, T., Masuzaki, H., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1258-2 · Cited by 102
“Furthermore, it has been demonstrated that leptin administration decreases liver and skeletal muscle triacylglycerol contents in patients with lipodystrophy [40].”
BackgroundVankoningsloo, S., Pauw, A. D., Houbion, A., Tejerina, S., Demazy, C., de Longueville, F., Bertholet, V., Renard, P., Remacle, J., Holvoet, P., et al. (2006) · Journal of Cell Science · doi:10.1242/jcs.02848 · Cited by 96
“Whereas defects in adipocyte metabolism induced by mitochondrial dysfunction might influence muscle and liver metabolism because it has been associated with lipodystrophy and impairment of fatty acid oxidation in these tissues (Petersen et al., 2002), preadipocyte response to mitochondrial dysfunction is still poorly…”
AMP-Activated Protein Kinase Is Not Down-Regulated in Human Skeletal Muscle of Obese Females
Steinberg, G. R., Smith, A. C., van Denderen, B. J. W., Chen, Z., Murthy, S., Campbell, D. J., Heigenhauser, G. J. F., Dyck, D. J., & Kemp, B. E. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0308 · Cited by 97
Changes in body composition in patients with severe lipodystrophy after leptin replacement therapy
Moran, S. A., Patten, N., Young, J. R., Cochran, E., Sebring, N., Reynolds, J., Premkumar, A., Depaoli, A. M., Skarulis, M. C., Oral, E. A., et al. (2004) · Metabolism · doi:10.1016/j.metabol.2003.10.019 · Cited by 96
Self-citationKalra, S. P. (2007) · Peptides · doi:10.1016/j.peptides.2007.10.017 · Cited by 98
Triantafyllou, G. A., Paschou, S. Α., & Mantzoros, C. S. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2016.04.012 · Cited by 101
Simha, V., Subramanyam, L., Szczepaniak, L. S., Quittner, C., ADAMS-HUET, B. A., Snell, P. G., & Garg, A. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2229 · Cited by 96
“Leptin Therapy for Lipodystrophy J Clin Endocrinol Metab, March 2012, 97(3):785–792”
BackgroundResultThe transcription factors Egr1 and Egr2 have opposing influences on adipocyte differentiation
Boyle, K. B., Hadaschik, D., Virtue, S., Cawthorn, W. P., Ridley, S. H., O’Rahilly, S., & Siddle, K. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.11 · Cited by 96
PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance
Crosson, S. M., Khan, A. H., Printen, J. A., Pessin, J. E., & Saltiel, A. R. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17975 · Cited by 95
“Indeed, both mouse models (32) and humans (33) with lipodystrophy undergo lipid accumulation in muscle that can be reversed by treatment with hormones such as leptin that increase lipid oxidation.”
BackgroundAssociation of onset of obesity with sleep duration and shift work among Japanese adults
Itani, O., Kaneita, Y., Murata, A., Yokoyama, E., & Ohida, T. (2011) · Sleep Medicine · doi:10.1016/j.sleep.2010.09.007 · Cited by 97
“In addition, it is known that administration of leptin decreases the serum level of triglyceride [30,31].”
BackgroundClinical Classification and Treatment of Congenital and Acquired Lipodystrophy
Chan, J. L., & Oral, E. A. (2010) · Endocrine Practice · doi:10.4158/ep09154.ra · Cited by 93
Leptin and Soluble Leptin Receptor Levels in Plasma and Risk of Type 2 Diabetes in U.S. Women
Sun, Q., van Dam, R. M., Meigs, J. B., Franco, O. H., Mantzoros, C. S., & Hu, F. B. (2009) · Diabetes · doi:10.2337/db09-1343 · Cited by 93
“Although intervention studies conducted in leptin-deficient animal models and humans supported a beneficial effect of leptin on insulin sensitivity or type 2 diabetes (43-47), prospective epidemiologic data on circulating leptin levels and future risk of type 2 diabetes have been mixed in subjects with normal leptin s…”
BackgroundRegulatory role of leptin in glucose and lipid metabolism in skeletal muscle
Minokoshi, Y., Toda, C., & Okamoto, S. (2012) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.105573 · Cited by 97
“[10,11] It has been demonstrated that treatment with leptin decreases lipid accumulation in nonadipose tissues and improves severe diabetes in lipodystrophy patients as well as rodents.[5,8-10]”
BackgroundSevere insulin resistance syndromes
Angelidi, A. M., Filippaios, A., & Mantzoros, C. S. (2021) · Journal of Clinical Investigation · doi:10.1172/jci142245 · Cited by 114
“In patients taking metreleptin, improved peripheral glucose disposal, hepatic glucose output, and insulin secretion lowered fasting glucose levels (182).”
BackgroundPerry, R. J., Resch, J. M., Douglass, A. M., Madara, J. C., Rabin-Court, A., Kucukdereli, H., Wu, C., Song, J. D., Lowell, B. B., & Shulman, G. I. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901795116 · Cited by 95
Sun, Q., Cornelis, M. C., Kraft, P., Qi, L., van Dam, R. M., Girman, C. J., Laurie, C. C., Mirel, D. B., Gong, H., Sheu, C., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq056 · Cited by 91
Mitochondrial function in ageing: coordination with signalling and transcriptional pathways
Yin, F., Sancheti, H., Liu, Z., & Cadenas, E. (2015) · The Journal of Physiology · doi:10.1113/jp270541 · Cited by 93
“Thus, modulation of energy homeostasis presents an interesting target against metabolic conditions like insulin resistance, obesity and type 2 diabetes (Petersen et al. 2002).”
BackgroundPetersen, K. F., Dufour, S., Morino, K., Yoo, P. S., Cline, G. W., & Shulman, G. I. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205675109 · Cited by 94
Sex and the course of HIV infection in the pre- and highly active antiretroviral therapy eras
Prins, M., Meyer, L., & Hessol, N. A. (2005) · AIDS · doi:10.1097/01.aids.0000161765.75663.27 · Cited by 91
“Studies of HIV-uninfected individuals with acquired and congenital lipodystrophy also demonstrated an association with insulin resistance, hypertriglyceridemia, and steatosis [135,136].”
BackgroundMolecular and Cellular Bases of Lipodystrophy Syndromes
Zammouri, J., Vatier, C., Capel, É., Auclair, M., Storey, C., Bismuth, É., Mosbah, H., Donadille, B., Janmaat, S., Fève, B., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.803189 · Cited by 95
Beltrand, J., Beregszàszi, M., Chevenne, D., Sebag, G. H., de Kerdanet, M., Huet, F., Polak, M., Tubiana‐Rufi, N., Lacombe, D., Paoli, A. M. D., et al. (2007) · PEDIATRICS · doi:10.1542/peds.2006-3165 · Cited by 89
Eosinophils support adipocyte maturation and promote glucose tolerance in obesity
Lee, E. H., Itan, M., Jang, J., Gu, H.-J., Rozenberg, P., Mingler, M. K., Wen, T., Yoon, J.-Y., Park, S., Roh, J. Y., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-28371-4 · Cited by 88
Defect of insulin signal in peripheral tissues: Important role of ceramide
Hassan, R. H. (2014) · World Journal of Diabetes · doi:10.4239/wjd.v5.i3.244 · Cited by 97
Osteoclasts and the immune system
Nakashima, T., & Takayanagi, H. (2009) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-009-0089-z · Cited by 88
Petersen, K. F., & Shulman, G. I. (2006) · Obesity · doi:10.1038/oby.2006.280 · Cited by 87
“These patients were found to have severe insulin resistance in both liver and muscle, which was associated with severe hepatic steatosis, but surprisingly, no increment of intramyocellular lipid, despite severe muscle insulin resistance (34).”
BackgroundSelf-citationPathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease
Akhtar, D. H., Iqbal, U., Vazquez‐Montesino, L. M., Dennis, B. B., & Ahmed, A. (2019) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2019.00028 · Cited by 89
“Initial studies involving patients with generalized lipodystrophy and lipodystrophic mouse models showed significant hepatic insulin resistance and recovery of insulin action post- leptin therapy and fat transplantation respectively.(51,52) These findings were augmented”
BackgroundETO/MTG8 Is an Inhibitor of C/EBPβ Activity and a Regulator of Early Adipogenesis
Rochford, J. J., Semple, R. K., Laudes, M., Boyle, K. B., Christodoulides, C., Mulligan, C., Lelliott, C. J., Schinner, S., Hadaschik, D., Mahadevan, M., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.22.9863-9872.2004 · Cited by 87
“Studies of obese and lipodystrophic humans and rodents demonstrate that both increased and decreased adipose tissue mass are associated with insulin resistance and abnormal glucose and lipid metabolism (17, 24, 29).”
BackgroundNonalcoholic steatohepatitis: recent advances from experimental models to clinical management
Portincasa, P., Grattagliano, I., Palmieri, V. O., & Palasciano, G. (2004) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2004.10.014 · Cited by 86
Cardiomyopathy in Congenital and Acquired Generalized Lipodystrophy
Lupsa, B. C., Sachdev, V., Lungu, A. O., Rosing, D. R., & Görden, P. (2010) · Medicine · doi:10.1097/md.0b013e3181e9442f · Cited by 86
Central Leptin Receptor Action and Resistance in Obesity
Bjørbæk, C. (2009) · Journal of Investigative Medicine · doi:10.2310/jim.0b013e3181bb0d49 · Cited by 88
Fontes‐Villalba, M., Lindeberg, S., Granfeldt, Y. E., Knop, F. K., Memon, A. A., Carrera‐Bastos, P., Picazo, Ó., Chanrai, M., Sunquist, J., Sundquist, K., et al. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0398-1 · Cited by 85
“It has been shown that treatment with recombinant human leptin does not improve insulin sensitivity in obese patients with type 2 diabetes [28], contrary to what happens in patients with severe leptin deficiency [29].”
BackgroundSphingolipid metabolism in non-alcoholic fatty liver diseases
Régnier, M., Polizzi, A., Guillou, H., & Loiseau, N. (2018) · Biochimie · doi:10.1016/j.biochi.2018.07.021 · Cited by 88
Roubíček, T., Bártlová, M., Krajickova, J., Haluzíková, D., Mráz, M., Lacinová, Z., Kudla, M., Teplan, V., & Haluzík, M. (2009) · Nutrition · doi:10.1016/j.nut.2008.12.012 · Cited by 85
“Clinical and experimental studies have demonstrated that administration of some adipose tissue-derived hormones such as leptin or adiponectin may have significant insulin-sensitizing, anti-inflammatory, and antiatherogenic effects [10–15].”
Mitochondrial dysfunction and type 2 diabetes
Parish, R., & Petersen, K. F. (2005) · Current Diabetes Reports · doi:10.1007/s11892-005-0006-3 · Cited by 84
Wolfgang, M. J., & Lane, M. D. (2006) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.25.050304.092532 · Cited by 85
Cochran, E., Young, J. R., Sebring, N., DePaoli, A., Oral, E. A., & Gorden, P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031952 · Cited by 83
“severely insulin-resistant lipodystrophic patients (5, 6).”
BackgroundSelf-citationNeuroprotective effects of leptin in the context of obesity and metabolic disorders
Davis, C., Mudd, J., & Hawkins, M. A. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.04.012 · Cited by 84
Adipose tissue dysfunction in obesity and lipodystrophy
Garg, A. (2006) · Clinical cornerstone · doi:10.1016/s1098-3597(06)80039-6 · Cited by 80
Huynh, F. K., Neumann, U. H., Wang, Y., Rodrigues, B. B., Kieffer, T. J., & Covey, S. D. (2012) · Hepatology · doi:10.1002/hep.26043 · Cited by 79
Understanding the cause of type 2 diabetes
Taylor, R. (2024) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(24)00157-8 · Cited by 88
Knights, A. J., Funnell, A. P. W., Pearson, R. C. M., Crossley, M., & Bell-Anderson, K. S. (2014) · Adipocyte · doi:10.4161/adip.27552 · Cited by 83
“Chronic leptin treatment may be clinically relevant in type 1 diabetes and lipodystrophic conditions to help steady glucose homeostasis.(60,64) The development of leptin resistance in the overweight and obese limits its use as an effective weight loss and insulin-sensitizing drug in this population.”
BackgroundRationale for Leptin-Replacement Therapy for Severe Lipodystrophy
Oral, E. A., & Chan, J. L. (2010) · Endocrine Practice · doi:10.4158/ep09155.ra · Cited by 77
Silha, J. V., Kršek, M., Hána, V., Marek, J., Ježková, J., Weiss, V., & Murphy, L. J. (2003) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2003.01789.x · Cited by 74
“In contrast, lipodystrophies have also been associated with insulin resistance both in man (Petersen et al. , 2002) and mouse models (Reitman et al. , 1999).”
BackgroundThe genetics of lipid storage and human lipodystrophies
Robbins, A. L., & Savage, D. B. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.04.004 · Cited by 76
Auer, M. K., Ebert, T., Pietzner, M., Defreyne, J., Fuss, J., Stalla, G. K., & T’Sjoen, G. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01559 · Cited by 75
“Leptin is an adipokine that reverses insulin resistance in metabolic disease states such as lipodystrophy (46).”
BackgroundPrior, S. J., Joseph, L., Brandauer, J., Katzel, L. I., Hagberg, J. M., & Ryan, A. S. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2113 · Cited by 74
Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle
Steinberg, G. R., Smith, A. C., Wormald, S., Malenfant, P., Collier, C., & Dyck, D. J. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00302.2003 · Cited by 73
Kim, J. K., Kim, H., Park, S., Cederberg, A., Westergren, R., Nilsson, D., Higashimori, T., Cho, Y.-R., Liu, Z., Dong, J., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1657 · Cited by 75
Meehan, C. A., Cochran, E. K., Kassai, A., Brown, R. J., & Görden, P. (2015) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2016.1096772 · Cited by 74
“The next major effects of metreleptin treatment are improvement in the marked dyslipidemia, including extreme elevation of triglycerides in serum and ectopic tissues,[28] as well as insulin resistance and diabetes.”
BackgroundMiyamoto, L., Ebihara, K., Kusakabe, T., Aotani, D., Yamamoto‐Kataoka, S., Sakai, T., Aizawa‐Abe, M., Yamamoto, Y., Fujikura, J., Hayashi, T., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.384545 · Cited by 74
“We and others have demonstrated that leptin effectively improves insulin sensitivity accompanied by dramatic reduction of fat content in the liver and skeletal muscle in patients with lipodystrophy (3,9-12).”
BackgroundLoss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin-deficient mice
Singhal, N. S., Patel, R. T., Qi, Y., Lee, Y.-S., & Ahima, R. S. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00577.2007 · Cited by 71
The dynamic interplay between osteoclasts and the immune system
Nakashima, T., & Takayanagi, H. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.04.004 · Cited by 72
Huang, W., Dedousis, N., Bhatt, B. A., & O'Doherty, R. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401546200 · Cited by 72
Cooperation Between Insulin and Leptin in the Modulation of Vascular Tone
Vecchione, C., Aretini, A., Maffei, A., Marino, G., Selvetella, G., Poulet, R., Trimarco, V., Frati, G., & Lembo, G. (2003) · Hypertension · doi:10.1161/01.hyp.0000082806.73530.68 · Cited by 72
Gibson, F., & Froguel, P. (2004) · Diabetes · doi:10.2337/diabetes.53.11.2977 · Cited by 70
“It has also become clear that adipose tissue rather than being a passive energy storehouse is, in fact, an active endocrine organ secreting a variety of proteins that regulate glucose levels, lipid metabolism, and energy homeostasis (5–7), including leptin (8,9), tumor necrosis factor- (10,11), and resistin (12,13).”
BackgroundThe Causal Role of Ectopic Fat Deposition in the Pathogenesis of Metabolic Syndrome
Janssen, J. A. M. J. L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413238 · Cited by 75
Owen, K. R., Donohoe, M. E., Ellard, S., & Hattersley, A. T. (2003) · Diabetic Medicine · doi:10.1046/j.1464-5491.2003.01034.x · Cited by 69
Advances in the Understanding and Treatment of Nonalcoholic Fatty Liver Disease
Harrison, S. A., & Bisceglie, A. M. D. (2003) · Drugs · doi:10.2165/00003495-200363220-00001 · Cited by 69
Krssak, M., & Roden, M. (2004) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/b:remd.0000021434.98627.dc · Cited by 68
“2), in women with previous gestational diabetes [64], in obese [65] and in insulin resistant lipodystrophic patients [66,67].”
BackgroundRodrı́guez, A., Moreno‐Castellanos, N., Balaguer, I., Méndez-Giménez, L., Becerril, S., Catalán, V., Gómez‐Ambrosi, J., Portincasa, P., Calamita, G., Soveral, G., et al. (2015) · Scientific Reports · doi:10.1038/srep12067 · Cited by 68
Lipodystrophy: A paradigm for understanding the consequences of "overloading" adipose tissue
Lim, K., Haider, A., Adams, C., Sleigh, A., & Savage, D. B. (2020) · Physiological Reviews · doi:10.1152/physrev.00032.2020 · Cited by 71
Inherited lipodystrophies and hypertriglyceridemia.
Simha, V., & Garg, A. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32832d4a33 · Cited by 67
Bocci, V. A., Zanardi, I., Huijberts, M. S., & Travagli, V. (2010) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2010.05.014 · Cited by 68
Goedeke, L., Peng, L., Montalvo-Romeral, V., Butrico, G. M., Dufour, S., Zhang, X.-M., Perry, R. J., Cline, G. W., Kievit, P., Chng, K., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aay0284 · Cited by 63
Li, H., Zhang, Y., Luo, H., & Lin, R. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.977625 · Cited by 68
“On the other hand, leptin therapy can resolve hepatic steatosis and ultimately improve insulin function (36).”
BackgroundParker, V., & Semple, R. K. (2013) · European Journal of Endocrinology · doi:10.1530/eje-13-0327 · Cited by 66
Mechanism for leptin’s acute insulin-independent effect to reverse diabetic ketoacidosis
Perry, R. J., Peng, L., Abulizi, A., Kennedy, L., Cline, G. W., & Shulman, G. I. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88477 · Cited by 68
“Based on these results, we hypothesize that the chronic effect of leptin can be attributed at least in part to its ability to (a) decrease hyperphagia, resulting in reductions in postprandial hyperglycemia; (b) lower ectopic lipid (DAG) content in liver and skeletal muscle, resulting in reversal of insulin resistance…”
BackgroundSelf-citationFree fatty acid processing diverges in human pathologic insulin resistance conditions
Sekizkardes, H., Chung, S. T., Chacko, S. K., Haymond, M. W., Startzell, M. S., Walter, M. F., Walter, P. J., Lightbourne, M., & Brown, R. J. (2020) · Journal of Clinical Investigation · doi:10.1172/jci135431 · Cited by 64
“Consistent with prior observations, our subjects with post-receptor insulin resistance due 248 to lipodystrophy had markedly elevated hepatic triglyceride (13-16), whereas subjects with receptor-level 249 insulin resistance due to INSR pathogenic variants did not develop hepatic steatosis despite extreme insulin 250 r…”
ResultEffects of Metreleptin in Pediatric Patients With Lipodystrophy
Brown, R. J., Meehan, C. A., Cochran, E., Rother, K. I., Kleiner, D. E., Walter, M., & Gorden, P. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-3628 · Cited by 65
“0001), and did not change in children [from 51 U/L (32, 99) to 40 U/L (24, 64); P = 0.”
ResultInfluentialNAFLD/NASH in patients with type 2 diabetes and related treatment options
Radaelli, M. G., Martucci, F., Perra, S., Accornero, S., Castoldi, G., Lattuada, G., Manzoni, G., & Perseghin, G. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0799-3 · Cited by 63
Shen, Y., Chen, W., Han, L., Bian, Q., Fan, J., Cao, Z., Jin, X., Ding, T., Xian, Z., Guo, Z., et al. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.07.002 · Cited by 63
Novel therapeutics for type 2 diabetes: insulin resistance
Altaf, Q. A., Barnett, A. H., & Tahrani, A. A. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12400 · Cited by 66
“Chronic treatment with recombinant leptin improved insulin sensitivity significantly in patients with diabetes and severe, generalized lipodystrophy when compared with age-, weight- and BMI-matched healthy controls [75].”
Backgroundp53 as a Dichotomous Regulator of Liver Disease: The Dose Makes the Medicine
Krstić, J., Galhuber, M., Schulz, T. J., Schupp, M., & Prokesch, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030921 · Cited by 65
“Data from lipodystrophic mice and patients with generalized lipodystrophy show a co-occurrence of hepatic insulin resistance and steatosis as a consequence of ectopic lipid deposition in the absence of white adipose tissue [51,52].”
BackgroundHepatic triglyceride contents are genetically determined in mice: results of a strain survey
Lin, X., Yue, P., Chen, Z., & Schonfeld, G. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00411.2004 · Cited by 63
Leptin Increases Hepatic Triglyceride Export via a Vagal Mechanism in Humans
Metz, M., Beghini, M., Wolf, P. S., Pfleger, L., Hackl, M. T., Bastian, M., Freudenthaler, A., Harreiter, J., Zeyda, M., Baumgartner-Parzer, S. M., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.020 · Cited by 65
Gonçalves, G. H. M., Li, W., Garcia, A. V. C.-G., Figueiredo, M. S., & Bjørbæk, C. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.010 · Cited by 64
Viewpoints on the Way to the Consensus Session
Iozzo, P. (2009) · Diabetes Care · doi:10.2337/dc09-s304 · Cited by 63
Nasrallah, M., & Ziyadeh, F. N. (2013) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2012.12.005 · Cited by 60
Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism in High Fat Diet-induced Obesity
Walton, R. G., Zhu, B., Ünal, R., Spencer, M. L., Sunkara, M., Morris, A. J., Charnigo, R. J., Katz, W. S., Daugherty, A., Howatt, D. A., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.628487 · Cited by 61
Zoccali, C., Tripepi, G. L., Cambareri, F., Catalano, F., Finocchiaro, P., Cutrupi, S., Pizzini, P., Testa, A., Spoto, B., Panuccio, V. A., et al. (2005) · Journal of Renal Nutrition · doi:10.1053/j.jrn.2004.09.036 · Cited by 59
Leptin in congenital and HIV-associated lipodystrophy
Tsoukas, M. A., Farr, O. M., & Mantzoros, C. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.07.017 · Cited by 58
“[101] Total liver volume decreases with leptin replacement, likely as a result of decreased intrahepatic lipid content, although decreases due to a decrease of intrahepatic glycogen have also been proposed.”
BackgroundInfluentialNonalcoholic fatty liver disease and lipids
Wierzbicki, A. S., & Oben, J. A. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283541cfc · Cited by 57
“Leptin therapy for lipodysstrophy improves hepatic insulin resistance and steatosis in humans [14].”
BackgroundRethinking leptin and insulin action: Therapeutic opportunities for diabetes
Yıldız, B. O., & Haznedaroğlu, İ. C. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.09.013 · Cited by 58
Neuroendocrine alterations in the exercising human: Implications for energy homeostasis
Fuqua, J. S., & Rogol, A. D. (2013) · Metabolism · doi:10.1016/j.metabol.2013.01.016 · Cited by 60
“[30] Petersen KF, Oral EA, Dufour S, et al.”
BackgroundLeptin Deficiency Contributes to the Pathogenesis of Alcoholic Fatty Liver Disease in Mice
Tan, X., Sun, X., Li, Q., Zhao, Y., Zhong, W. H., Sun, X., Jia, W. P., McClain, C. J., & Zhou, Z. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.06.013 · Cited by 57
In vivo leptin infusion impairs insulin and leptin signalling in liver and hypothalamus
Benomar, Y., Wetzler, S., Larue‐Achagiotis, C., Djiane, J., Tomé, D., & Taouis, M. (2005) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2005.07.003 · Cited by 57
Current perspectives on HIV-associated lipodystrophy syndrome
Milinkovic, A., & Martínez, E. (2005) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dki165 · Cited by 56
Aging adipose tissue, insulin resistance, and type 2 diabetes
Zhao, Y., & Yue, R. (2023) · Biogerontology · doi:10.1007/s10522-023-10067-6 · Cited by 57
“In addition, leptin has a positive effect on reducing peripheral insulin resistance and hyper-glycemia (Petersen et al. 2002).”
Multiple organs involved in the pathogenesis of non-alcoholic fatty liver disease
Li, X., & Wang, H. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00507-y · Cited by 59
“Leptin downregulates the transcription of the preproinsulin gene and insulin excretion, and high levels of leptin were documented in obese individuals or during IR [75, 76].”
Background
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.
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