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
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Self-citationEffects of Recombinant Leptin Therapy in a Child with Congenital Leptin Deficiency
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Self-citationLeptin-Replacement Therapy for Lipodystrophy
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Self-citationLeptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy
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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 401–500 of 797
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Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives
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“None of these recurred or persisted with continued therapy Petersen [39] NIH 20010796 3 (2 CGL, 1 AGL) 17, 26, 35 0.03 mg/kg/d (F < 18 y), 0.05 mg/kg/d (F > 18 y)§ 8 Decreased fasting glucose, increased insulin sensitivity, discontinued diabetic medications, improved hepatic production of glucose, decreased muscle tri…”
BackgroundInfluentialAmerican College of Endocrinology Pre-Diabetes Consensus Conference: Part Two
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“Shulman reviewed studies of individuals with lipodystrophy in which leptin administration for 6 months normalized fasting glucose, with improvement in insulin-stimulated muscle glucose uptake (38).”
BackgroundPeroxisome Proliferator-Activated Receptor-??
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Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis
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Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
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Therapeutic use of recombinant methionyl human leptin
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Effect of Chinese prescription Kangen-karyu on lipid metabolism in type 2 diabetic db/db mice
Yamabe, N., Kim, H. Y., Kang, K. S., Zhao, Q., Matsumoto, K., & Yokozawa, T. (2010) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2010.03.032 · Cited by 26
The therapeutic potential of leptin
Proietto, J., & Thorburn, A. W. (2003) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.12.3.373 · Cited by 26
“Leptin treatment has been shown to be beneficial [48,49].”
BackgroundGillingham, M. B., Harding, C. O., Schoeller, D. A., Matern, D., & Purnell, J. Q. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00225.2013 · Cited by 25
Yu, J. H., Ahn, J. H., Yoo, H. J., Seo, J. A., Kim, S. G., Choi, K. M., Baik, S. H., Choi, D. S., Shin, C., & Kim, N. H. (2015) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2015.30.6.846 · Cited by 25
“Additionally, patients with severe lipodystrophy develop severe hepatic steatosis and hepatic insulin resistance in the absence of visceral obesity [33], Table 2.”
BackgroundShi, T., Papay, R. S., & Perez, D. M. (2016) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2016.1193522 · Cited by 25
“Leptin improves insulin sensitivity by reducing fat content in the liver and skeletal muscle (41,42).”
BackgroundSodium–Glucose Cotransporter 2 Inhibitor Improves Complications of Lipodystrophy: A Case Report
Kawana, Y., Imai, J., Sawada, S., Yamada, T., & Katagiri, H. (2017) · Annals of Internal Medicine · doi:10.7326/l16-0372 · Cited by 25
Recent developments in lipodystrophy
Melvin, A., Stears, A. J., & Savage, D. B. (2019) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000613 · Cited by 25
“Exogenous leptin therapy in patients with hypoleptinemic lipodystrophy reduces caloric intake and it is believed that this is the major factor contributing to the favorable metabolic effects of leptin replacement therapy in lipodystrophy [32,28].”
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A rapid action plan to improve diagnosis and management of lipodystrophy syndromes
Fourman, L. T., Lima, J. G., Simha, V., Cappa, M., Al-Yaarubi, S., Montenegro, R. M., Akıncı, B., & Santini, F. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1383318 · Cited by 24
“Further studies at the NIH and other treatment centers showed that metreleptin decreased hyperphagia (17), improved insulin sensitivity (91, 92), reduced liver steatosis and improved NASH score on biopsy specimens (30, 93).”
BackgroundCarbone, F., Mach, F., Pontremoli, R., Viazzi, F. C., & Montecucco, F. (2013) · Thrombosis and Haemostasis · doi:10.1160/th13-06-0499 · Cited by 25
“Experimental evidence from a mouse model of lipoatrophy (46) and patients with severe lipodystrophy (47) might support this hypothesis.”
BackgroundCholic acid for hepatic steatosis in patients with lipodystrophy: a randomized, controlled trial
Ahmad, Z., Subramanyam, L., Szczepaniak, L. S., Simha, V., ADAMS-HUET, B. A., & Garg, A. (2013) · European Journal of Endocrinology · doi:10.1530/eje-12-0969 · Cited by 23
Role of Leptin in the Digestive System
Kim, M., & Kim, H. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.660040 · Cited by 27
“Therefore, administration of human recombinant leptin improves many metabolic defects in patients with lipodystrophy (Petersen et al., 2002).”
BackgroundEffects of Leptin Replacement Therapy on Pancreatic β-Cell Function in Patients With Lipodystrophy
Muniyappa, R., Brown, R. J., Mari, A., Joseph, J., Warren, M. A., Cochran, E. K., Skarulis, M. C., & Görden, P. (2014) · Diabetes Care · doi:10.2337/dc13-2040 · Cited by 24
“09), it is possible that a more sensitive method, such as the euglycemic-hyperinsulinemic clamp, would have detected improvements in insulin sensitivity as reported in prior studies (1,24,30).”
MethodMoon, H., Huh, J. Y., Dincer, F., Schneider, B. E., Hasselgren, P., & Mantzoros, C. S. (2014) · Diabetes · doi:10.2337/db14-0625 · Cited by 24
“Leptin replacement therapy has been reported to be effective in improving insulin resistance and the metabolic profile in these patients (11-13).”
BackgroundAdiponectin and hypertension: a putative link between adipocyte function and atherosclerotic risk?
Patel, J. V., Lim, H. S., Hughes, E. A., & Lip, G. Y. H. (2006) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1002078 · Cited by 24
“10 The metabolic importance of adipose function is highlighted by studies in patients with lypodystrophy, where paradoxically, features of the metabolic syndrome are frequently manifest despite the lack of adipose tissue – possibly reflecting (at least in part) a lack of adipocytokine activity”
BackgroundThe metabolic syndrome and type 2 diabetes: role of the adipocyte
McPherson, R., & Jones, P. H. (2003) · Current Opinion in Lipidology · doi:10.1097/00041433-200312000-00001 · Cited by 24
Inflammatory osteoclastogenesis can be induced by GM-CSF and activated under TNF immunity
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Leptin therapy in type 2 diabetes
Cummings, B. P. (2012) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12048 · Cited by 24
“Similarly, studies of leptin replacement therapy in lipodystrophic patients report improvements of insulin sensitivity with coinciding decreases of hepatic lipid deposition [25,26].”
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“Leptinmayalsoprevent the“lipotoxic”effects of intramyocellular lipid accumulation by activating fatty acids oxidation in skeletal muscle (7).”
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AMP-activated protein kinase and malonyl-CoA: Targets for treating insulin resistance?
Ye, J., Ruderman, N. B., & Kraegen, E. W. (2005) · Drug Discovery Today Therapeutic Strategies · doi:10.1016/j.ddstr.2005.05.019 · Cited by 23
Leptin in Relation to the Lipodystrophy-Associated Metabolic Syndrome
Mantzoros, C. S. (2012) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2012.36.3.181 · Cited by 22
“Hyperglycemic-euglycemic clamps in three patients with lipoatrophic diabetes have shown remarkable improvement in insulin sensitivity after leptin treatment [26].”
BackgroundInfluentialMETABOLIC SYNDROME: CHALLENGING AND UNRESOLVED ISSUES
Чумакова, Г. А., Veselovskaya, N. G., Gritsenko, O. V., & Ott, A. (2014) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2014-3-63-71 · Cited by 22
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Consequences of Stopping and Restarting Leptin in an Adolescent with Lipodystrophy
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Relationship between Serum Leptin Concentration and Low-Density Muscle in Postmenopausal Women
Muñoz, J. A., & Gower, B. A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020959 · Cited by 22
“Insulin sensitivity is likewise improved by leptin treatment in human patients with lipodystrophy in the absence of weight loss, but with a reduction in IML (24).”
BackgroundEffect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients
Levenson, A. E., Haas, M. E., Miao, J., Brown, R. J., de Ferranti, S. D., Muniyappa, R., & Biddinger, S. B. (2016) · Endocrinology · doi:10.1210/en.2015-1624 · Cited by 22
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“Numerous studies have demonstrated the capacity of chronic leptin administration to improve insulin sensitivity, as it pertains to glucose metabolism (8, 9, 11, 13).”
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Potential Mechanisms for How Long-Term Physical Activity May Reduce Insulin Resistance
Lee-Ødegård, S., Olsén, T., Norheim, F., Drevon, C. A., & Birkeland, K. I. (2022) · Metabolites · doi:10.3390/metabo12030208 · Cited by 20
The Clinical Application of Ozonetherapy
Bocci, V. A. (2010) · Springer eBooks · doi:10.1007/978-90-481-9234-2_9 · Cited by 24
“Lipodistrophy seemingly due to ineffective leptin activity or/and fatty acids dysmetabolism (Petersen et al., 2002; Unger, 2002; Minokoshi et al., 2002).”
BackgroundLack of kinin B1 receptor potentiates leptin action in the liver
Fonseca, R. G., Sales, V., Ropelle, E. R., et al. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1004-6 · Cited by 21
“It can reduce, by central or direct mechanisms, hepatic stores of triglycerides by modulating the expression of genes involved in the synthesis and oxidation of lipids [23, 24].”
BackgroundRuiter, M., Buijs, R. M., & Kalsbeek, A. (2006) · Current Diabetes Reviews · doi:10.2174/157339906776818596 · Cited by 22
“Leptin, for example, directly influences both endocrine and exocrine pancreatic function [211] and energy metabolism [147, 176, 203].”
BackgroundIntracellular lipid accumulation and shift during diabetes progression
Wolf, P. S., Winhofer, Y., Anderwald, C. H., Krššák, M., & Krebs, M. (2014) · Wiener Medizinische Wochenschrift · doi:10.1007/s10354-014-0292-y · Cited by 20
Serum visfatin levels in acromegaly: Correlation with disease activity and metabolic alterations
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“The alteration in visceral adiposity, both in excess and in deficiency, has been shown to be a main determinant of insulin resistance in non-acromegalic patients [21,22] and this relationship ismediated by adipokine secretion that may modulate insulin sensitivity [23].”
BackgroundLipid-Induced Insulin Resistance in the Liver
Katsanos, C. S. (2004) · Sports Medicine · doi:10.2165/00007256-200434140-00002 · Cited by 21
Insulin Resistance in Type 2 Diabetes
Roden, M., Petersen, K. F., & Shulman, G. I. (2016) · Wiley eBooks · doi:10.1002/9781118924853.ch13 · Cited by 20
Leptin therapy in lipodystrophy
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“What are the other options? Although some research in rodent models suggests that leptin may have beneficial effects on metabolic rate and even peripheral actions, most existing rodent data suggest that the dominant effect is a centrally mediated reduction in food intake [17, 18]; an observation borne out by available…”
BackgroundTrabucchi, A., Iacono, R. F., Guerra, L. L., Faccinetti, N. I., Krochik, G., Arriazu, M. C., Poskus, E., & Valdez, S. N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084099 · Cited by 21
“Another study has demonstrated that patients with severe lipodystrophy are sternly insulin resistant, which can be attributed to defects in insulin action in both liver and muscle [21].”
BackgroundEffects of Metreleptin on Proteinuria in Patients With Lipodystrophy
Lee, H. L., Waldman, M. A., Auh, S., Balow, J. E., Cochran, E. K., Görden, P., & Brown, R. J. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00200 · Cited by 19
do Carmo, J. M., da Silva, A. A., Gava, F. N., Moak, S. P., Dai, X., & Hall, J. E. (2019) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00077.2019 · Cited by 19
Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy
Grover, A., Quaye, E. M., Brychta, R. J., Christensen, J. D., Startzell, M. S., Meehan, C. A., Valencia, A., Marshall, B. D. L., Chen, K. Y., & Brown, R. J. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab269 · Cited by 21
Pathogenesis of insulin resistance
Choi, C. S. (2009) · The Korean Journal of Internal Medicine · Cited by 19
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Antioxidant Tempol Lowers Age-Related Increases in Insulin Resistance in Fischer 344 Rats
Asghar, M., & Lokhandwala, M. F. (2006) · Clinical and Experimental Hypertension · doi:10.1080/10641960600798697 · Cited by 19
Svensson, J., Herlitz, H., Lundberg, P., & Johannsson, G. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1239 · Cited by 19
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“Hepatic insulin resistance is associated with hepatic steatosis, which is highly prevalent in patients with type 2 diabetes [2,3].”
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Self-citationCyclin Y Is Involved in the Regulation of Adipogenesis and Lipid Production
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“Because WAT is an important endocrine organ and contributes to the metabolic state, a reduction in WATmight lead to lipodystrophy syndrome [4].”
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Acquired Generalized Lipodystrophy Associated with Autoimmune Hepatitis and Low Serum C4 Level
Eren, E., Özkan, T., Çakır, E. D. P., Sağlam, H., & Tarım, Ö. (2010) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.v2i1.39 · Cited by 18
“Recently, leptin therapy has been reported to correct hyperglycemia, dyslipidemia, and hepatic steatosis both in congenital and acquired forms of lipodystrophy (12-15).”
BackgroundMéndez‐Sánchez, N., Chávez-Tapia, N. C., Medina‐Santillán, R., Villa, A. R., Sánchez-Lara, K., Ponciano‐Rodríguez, G., Ramos, M. H., & Uribe, M. (2006) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-9093-5 · Cited by 18
“Leptin replacement in hypoleptinemic lipoatrophic patients, however, improved glucose tolerance and decreased serum insulin concentrations [34, 35].”
Backgroundla Cruz-Color, L. D., Domı́nguez-Rosales, J. A., Maldonado‐González, M., Ruiz‐Madrigal, B., Sánchez-Muñoz, M. P., Zaragoza-Guerra, V. A., Espinoza-Padilla, V. H., Ruelas-Cinco, E. D. C., Ramírez-Meza, S. M., Torres-Baranda, J. R., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126420 · Cited by 18
“Leptin resistance in humans is influenced by factors such as obesity, lipodystrophy, or genetic variations, comparable to the effects seen in individuals with LEPR polymorphisms and MASLD [27,37].”
BackgroundFoo, J., & Mantzoros, C. S. (2012) · Metabolism · doi:10.1016/j.metabol.2012.04.013 · Cited by 17
Resveratrol as a potential protective compound against skeletal muscle insulin resistance
Bahramzadeh, A., Bolandnazar, K., & Meshkani, R. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e21305 · Cited by 17
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“Quality assessment Quality percentage scores based on a modified QUADAS 2 tool ranged from 25% (30) to 75% (16,23), and the overall mean score was 56.”
BackgroundMethodInfluentialiNOS Gene Ablation Prevents Liver Fibrosis in Leptin-Deficient ob/ob Mice
Becerril, S., Rodrı́guez, A., Catalán, V., Ramírez, B., Unamuno, X., Gómez‐Ambrosi, J., & Frühbeck, G. (2019) · Genes · doi:10.3390/genes10030184 · Cited by 17
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“In addition, leptin plays a major role in liver lipid handling, as recombinant leptin reverses insulin resistance and hepatic steatosis in lipodystrophic patients [42].”
BackgroundNajdi, F., Krüger, P., & Djabali, K. (2021) · Cells · doi:10.3390/cells10071598 · Cited by 19
“Lipodystrophy is a rare disorder characterized by the total or partial loss of the adipose tissue [12].”
BackgroundTHE PATHOPHYSIOLOGY OF METABOLIC SYNDROME
Mendelson, S. D. (2008) · Elsevier eBooks · doi:10.1016/b978-012374240-7.50005-x · Cited by 18
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Mouse Embryonic Fibroblasts Protect ob/ob Mice From Obesity and Metabolic Complications
Ferguson, D., Blenden, M., Hutson, I., Du, Y., & Harris, C. A. (2018) · Endocrinology · doi:10.1210/en.2018-00561 · Cited by 16
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“In addition to its main effects, leptin also reduces ectopic lipid deposition in the liver and muscle [44].”
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Adipokines as key players in β cell function and failure
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Insulin Resistance: Causes and Consequences
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A Translational View of the Genetics of Lipodystrophy and Ectopic Fat Deposition
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“Moreover, leptin replacement in leptin-deficient, lipodystrophic animals [18] and human subjects [19,20] markedly reduces hepatic TG content and plasma TG concentrations.”
BackgroundCarlson, O. D., David, J. D., Schrieder, J. M., Muller, D. C., Jang, H.-J., Kim, B.-J., & Egan, J. M. (2007) · Metabolism · doi:10.1016/j.metabol.2007.06.009 · Cited by 16
“Several studies, including many recent ones, have implicated a number of adipocyte-derived factors such as leptin, resistin, and adiponectin in mediating insulin resistance in patients with type 2 diabetes mellitus [30-32].”
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Diagnosis and management of lipodystrophy: a practical update
Stears, A. J., & Hames, C. (2014) · Clinical Lipidology · doi:10.2217/clp.14.13 · Cited by 15
Adiponectin and leptin levels in normal weight women with polycystic ovary syndrome
Gözüküçük, M., Gürsoy, A. Y., Destegül, E., Taşkın, S., & Şatıroğlu, H. (2020) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2020-0016 · Cited by 15
“Leptin levels have been shown to reverse insulin resistance and diabetes mellitus in animal models and also patients with lipodystrophy [26, 27].”
BackgroundLeptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy
Nguyen, M., Sachdev, V., Burklow, T. R., Li, W., Startzell, M. S., Auh, S., & Brown, R. J. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab499 · Cited by 15
Two Japanese infants with congenital generalized lipodystrophy due to BSCL2 mutations
Nishiyama, A., Yagi, M., Awano, H., Okizuka, Y., Maeda, T., Yoshida, S., Takeshima, Y., & Matsuo, M. (2009) · Pediatrics International · doi:10.1111/j.1442-200x.2009.02863.x · Cited by 15
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“Indeed, early rodent models of leptin deficiency were characterized by insulin resistance and diabetes [34,35], conditions that have been shown to be ameliorated with leptin administration both in rodents and humans [36,37].”
BackgroundImmunohistochemical Evaluation of Leptin Expression in Wound Healing
Seleit, I., Bakry, O. A., Samaka, R. M., & Tawfik, A. S. (2015) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000000187 · Cited by 15
“Site [n (%)] Axial — 12 (60) 12 (60) 14 (70) Extremities 8 (40) 8 (40) 6 (30) Family history [n (%)] Positive — 0 (0.”
InfluentialCassidy, J. T., & Lindsley, C. B. (2005) · Elsevier eBooks · doi:10.1016/b978-1-4160-0246-8.50024-3 · Cited by 15
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“All BSS patients have insulin resistance that is associated with leptin resistance, and leptin treatment has been shown to reverse insulin resistance, which demonstrates the direct relationship between the two [ ,”
BackgroundLambadiari, V., Kountouri, A., Maratou, E., Liatis, S., Dimitriadis, G., & Karpe, F. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.684182 · Cited by 14
“These alterations are associated with a reduced hepatic and muscle triglyceride content (27).”
BackgroundLiu, X., Huang, L., Wu, Q., Chen, Y., Chen, X., Chen, H., Gao, J., & Xiao, Q. (2022) · BMC Geriatrics · doi:10.1186/s12877-022-03074-8 · Cited by 14
“Sleep disorders or short sleep duration can cause hypertension, overweight, obesity, type 2 diabetes, and dyslipidemia through affect sympathetic nerve activity [9], regulate leptin and ghrelin [10, 11], reduce insulin sensitivity, promote insulin resistance [12, 13], stimulate lipodieresis, increase plasma free fatty…”
BackgroundMetreleptin for metabolic disorders associated with generalized or partial lipodystrophy
Simha, V. (2014) · Expert Review of Endocrinology & Metabolism · doi:10.1586/17446651.2014.894877 · Cited by 13
“We [29] and other investigators [30] have reported significant decline in intrahepatic and intramyocellular lipid content following leptin therapy.”
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Lai, H., Lin, W., Chen, P., et al. (2005) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607105029006401 · Cited by 14
The role of adipose tissue as an endocrine gland
Hamdy, O. (2005) · Current Diabetes Reports · doi:10.1007/s11892-005-0086-0 · Cited by 14
“Leptin therapy in lipodystrophic patients was shown to improve glycemic control, improve insulin-stimulated hepatic and peripheral glucose metabolism, and to reduce hepatic and muscle triglyceride content, suggesting that leptin acts as a signal that contributes to regulation of total body sensitivity to insulin [ 13…”
BackgroundMG53 and disordered metabolism in striated muscle
Hu, X., & Xiao, R. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.10.013 · Cited by 13
Metadata
- Authors
- Petersen, K. F., Oral, E. A., Dufour, S., Befroy, D., Ariyan, C., Yu, C., Cline, G. W., DePaoli, A. M., Taylor, S. I., Gorden, P., & Shulman, G. I.
- Affiliations
- Yale University (US)
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Amgen (United States) (US)
- Corresponding author
- Petersen, Kitt Falk
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2002-05-15
- Volume
- 109
- Issue
- 10
- Pages
- 1345-1350
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC150981
- OpenAlex
- W2164714249
- Cited by
- 800
- References
- 26
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 20 · 2023: 21 · 2022: 23 · 2021: 27 · 2020: 25 · 2019: 29 · 2018: 29 · 2017: 31 · 2016: 38 · 2015: 39 · 2014: 34 · 2013: 45 · 2012: 35
- FWCI
- 26.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- Yale University
- National Institutes of Health (P30 DK)
- National Institute of Diabetes and Digestive and Kidney Diseases (K-23 DK-02347, R01 DK-42930, P30DK045735)
- National Center for Research Resources (M01RR000125)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- leptin, lipodystrophy, insulin resistance, hepatic steatosis, hepatic glucose metabolism, muscle glucose metabolism, triglyceride accumulation, hypertriglyceridemia, hepatomegaly
- MeSH terms
- Adult, Diabetes Mellitus, Type 2, Fatty Liver, Female, Humans, Insulin Resistance, Lipodystrophy, Liver, Hypertriglyceridemia, Leptin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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