The DOI matches its Crossref record; 43 of the 45 references it cites were found in a registry or an index; none of the 13 sources its claims cite is checked for support yet.
Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy†
Open accessAbstract
Severe lipodystrophy is characterized by diminished adipose tissue and hypoleptinemia, leading to ectopic triglyceride accumulation. In the liver, this is associated with steatosis, potentially leading to nonalcoholic steatohepatitis (NASH). We investigated the prevalence of NASH and the effect of leptin replacement in these patients. Ten patients with either generalized lipodystrophy (8 patients) or Dunnigan's partial lipodystrophy (2 patients) were included in this analysis. Paired liver biopsy specimens were obtained at baseline and after treatment with recombinant methionyl human leptin (r-metHuLeptin), mean duration 6.6 months. The extents of portal and parenchymal inflammation, steatosis, ballooning, presence of Mallory bodies, and fibrosis in liver biopsy specimens were scored using a previously validated system developed to assess NASH activity. Histological disease activity was defined as the sum of ballooning, steatosis, and parenchymal inflammation scores. We concurrently tested serum triglycerides and aminotransferases and estimations of liver volume and fat content by magnetic resonance imaging. Eight of 10 patients met histological criteria for NASH at baseline. After treatment with r-metHuLeptin, repeat histological examinations showed significant improvements in steatosis (P = .006) and ballooning injury (P = .005), with a reduction of mean NASH activity by 60% (P = .002). Fibrosis was unchanged. Significant reductions were seen in mean serum triglycerides (1206-->226 mg/dL, P = .002), glucose (220-->144 mg/dL, P = .02), insulin (46.4-->24.8 muIU/mL, P = .004), ALT (54-->24 U/L, P = .02), AST (47-->22 U/L, P = .046), liver volume (3209-->2391 cm(3), P = .007), and liver fat content (31-->11%, P = .006). In conclusion, r-metHuLeptin therapy significantly reduced triglycerides, transaminases, hepatomegaly, and liver fat content. These reductions were associated with significant reductions in steatosis and the hepatocellular ballooning injury seen in NASH.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In 10 patients with severe lipodystrophy and hypoleptinemia, recombinant methionyl human leptin (r-metHuLeptin) treatment was associated with significant histological improvement in nonalcoholic steatohepatitis (NASH), alongside reductions in liver fat, liver volume, triglycerides, and aminotransferases. Fibrosis did not change over the mean 6.6-month treatment period.
Key findings
- Eight of 10 patients met histological criteria for NASH at baseline; after r-metHuLeptin, 6 of the 8 (75%) no longer met those criteria, and the group prevalence of NASH fell from 80% to 20% (P = .03).
- Mean NASH activity score decreased by 60%, from 5.3 ± 0.8 to 2.1 ± 0.4 (P = .002), with significant improvements in steatosis (1.7 ± 0.4 to 0.4 ± 0.2; P = .006) and ballooning injury (1.5 ± 0.4 to 0.3 ± 0.2; P = .005); fibrosis was unchanged (1.9 ± 0.4 to 1.9 ± 0.5; P = .1).
- Mean serum triglycerides fell from 1,206 ± 590 to 226 ± 57 mg/dL (P = .002), fasting glucose from 220 ± 27 to 144 ± 13 mg/dL (P = .02), fasting insulin from 46.4 ± 13.0 to 24.8 ± 7.4 IU/mL (P = .004), ALT from 54 ± 13 to 24 ± 4 U/L (P = .02), and AST from 47 ± 11 to 22 ± 2 U/L (P = .046).
- Mean liver volume decreased from 3,209 ± 348 to 2,391 ± 254 cm³ (P = .007), and mean liver fat by MRI decreased from 31% ± 7% to 11% ± 6% (P = .006).
Methods
- Open-label pilot study of r-metHuLeptin in 10 patients with severe lipodystrophy: 4 congenital generalized lipodystrophy, 4 acquired generalized lipodystrophy, and 2 Dunnigan’s partial lipodystrophy; 8 female and 2 male, age range 17–67 years.
- Paired liver biopsies were obtained before and after treatment (mean duration 6.6 ± 1.4 months); biopsies were scored by a single hepatopathologist blinded to clinical data and biopsy sequence using a previously validated NASH scoring system.
- Concurrent laboratory testing and MRI assessments of liver volume and liver fat were performed; paired t tests or Wilcoxon signed-rank tests compared baseline and post-treatment means, and Spearman rank correlation assessed relationships between NASH score and metabolic/imaging variables.
Limitations
- The paper states limitations including relatively small sample size, variable interval between liver biopsies, study of a rare disease with uncertain general relationship to NASH, lack of placebo control, and no evidence that results in hypoleptinemic patients apply to broader NASH patients with higher serum leptin concentrations.
- The authors also state that the short interval between biopsies was the primary factor limiting observed change in fibrosis.
- Evident from the text: this was an open-label, single-arm pilot study without a placebo or untreated comparator, and the sample was predominantly female, which may limit generalizability.
Model-written summary. Check it against the paper before relying on it.
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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
“Fasting insulin (IU/mL) 46.4 Ϯ 13.0 24.8 Ϯ 7.4 .004”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
Strength:plain· not yet calibratedCausal:direct· 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
“The reductions in NASH scores were strongly correlated with reductions in liver volumes, liver fat measured by MRI, serum transami-nases, triglycerides, fasting insulin, and fasting glucose values (Table 3).”
- Also stated in: § Discussion · plain
“There were significant correlations between the NASH activity scores and MRI estimations of liver volume and fat content, serum transaminases, triglycerides, fasting insulin, and fasting glucose values.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > r-metHuLeptin Therapy
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ALT (U/L) 54 Ϯ 13 24 Ϯ 4 .02”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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
“Fasting glucose (mg/dL) 220 Ϯ 27 144 Ϯ 13 .02”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
Strength:plain· not yet calibratedCausal:direct· 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
“After treatment with r-metHuLeptin, repeat histological examinations showed significant improvements in steatosis (P ؍ .006)and ballooning injury (P ؍ .005),with a reduction of mean NASH activity by 60% (P ؍ .002).”
- Also stated in: § Discussion · plain
“Steatosis 1.7 Ϯ 0.4 0.4 Ϯ 0.2 .006”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Liver volume (cc) 3,209 Ϯ 348 2,391 Ϯ 254 .007”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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
“Eight of 10 patients met histological criteria for NASH at baseline.”
- Also stated in: § Baseline Liver Data · plain
“Eight patients had histological evidence of NASH.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Baseline Liver Data · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After treatment with r-metHuLeptin, repeat histological examinations showed significant improvements in steatosis (P ؍ .006)and ballooning injury (P ؍ .005),with a reduction of mean NASH activity by 60% (P ؍ .002).”
- Also stated in: § Discussion · plain
“Ballooning injury 1.5 Ϯ 0.4 0.3 Ϯ 0.2 .005”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HbA 1c (%) 8.5 Ϯ 0.3 6.7 Ϯ 0.4 .005”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
Strength:plain· not yet calibratedCausal:direct· 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
“Of the 9 patients who had steatosis at baseline, only 3 had steatosis on follow-up biopsy.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > r-metHuLeptin Therapy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 3
- Probably not a substantial claim. 18
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
“Similarly, of the 8 patients with ballooning hepatocellular injury, only 3 had ballooning identified in follow-up, and in all 3 the degree was mild and confined to zone 3.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > r-metHuLeptin Therapy
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
“Mallory bodies 0.6 Ϯ 0.3 0.2 Ϯ 0.2 .1”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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
“In addition to steatosis and inflammation, all 8 patients with steatohepatitis had ballooning hepatocellular injury varying from mild changes only in zone 3 to diffuse, panacinar ballooning changes and fibrosis that varied from mild perisinusoidal zone 3 fibrosis to cirrhosis.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Baseline Liver Data
Strength:plain· not yet calibratedn = 8Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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
“Only 3 patients had identifiable Mallory bodies, despite staining all biopsy specimens with anti-ubiquitin.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Baseline Liver Data
Strength:plain· not yet calibratedn = 3Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“However, the causative relationship of these correlations to the clinical situation remains uncertain.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A liver specimen of at least 15 mm with a minimum of 10 portal tracts was considered adequate for evaluation.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Histological Analysis
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The modified Dixon method was used to assess the hepatic fat fraction.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Liver Fat Measurements.
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.
In the paper
“The extents of portal and parenchymal inflammation, steatosis, ballooning, presence of Mallory bodies, and fibrosis in liver biopsy specimens were scored using a previously validated system developed to assess NASH activity.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Abstract
What the sources say
- Not checked yetcites [14] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Steatosis is believed to sensitize the liver to metabolic injury, leading to inflammation, necrosis, and fibrosis.2,[5][6][7]”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Abstract
What the sources say
Strength:hedged· 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Biopsy specimens were scored prospectively by a single hepatopathologist blinded to the clinical data and sequence of the biopsies using a previously described scoring method developed for NASH.14”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Histological Analysis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“The assessment and severity of NASH is made histologically based on the patterns and degrees of hepatic steatosis, inflammation, and injury, in the absence of significant alcohol consumption.8”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Abstract
What the sources say
- Not checked yetcites [8] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Other limitations of this study include its relatively small sample size, the variable interval between liver biopsies, the study of a rare disease in terms of its general relationship to NASH, and the fact that this study was not placebo-controlled.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent rodent studies suggest that this can be potentially overcome with a high enough dose, 22,24 a theory similar to insulin resistance.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
Strength:hedged· not yet calibratedCausal:conditional· 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 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
“Severe lipodystrophy is an exaggerated model of ectopic fat accumulation leading to an exaggerated form of the metabolic syndrome.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“This may have broader implications for NASH in the general population, which is also characterized by ectopic triglyceride accumulation and secondary disorders such as insulin resistance.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Other limitations of this study include its relatively small sample size, the variable interval between liver biopsies, the study of a rare disease in terms of its general relationship to NASH, and the fact that this study was not placebo-controlled.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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 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
“The leptin and thiazolidinedione models both demonstrate the association of NASH with steatosis and the reversal of NASH by removing the fat.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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
“Furthermore, we have no evidence that the results achieved in this population of patients with hypoleptinemia are relevant to the broader group of NASH patients with higher serum leptin concentrations.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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 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
“Other limitations of this study include its relatively small sample size, the variable interval between liver biopsies, the study of a rare disease in terms of its general relationship to NASH, and the fact that this study was not placebo-controlled.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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 conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In other words, insulin resistance and NASH appear to develop in parallel rather than sequentially.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Other limitations of this study include its relatively small sample size, the variable interval between liver biopsies, the study of a rare disease in terms of its general relationship to NASH, and the fact that this study was not placebo-controlled.”
§ Leptin Reverses Nonalcoholic Steatohepatitis in Patients With Severe Lipodystrophy > Discussion
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.
The paper relies on this without support.
Severe lipodystrophy is characterized by diminished adipose tissue and hypoleptinemia, leading to ectopic triglyceride accumulation.
“Severe lipodystrophy is characterized by diminished adipose tissue and hypoleptinemia, leading to ectopic triglyceride accumulation.”
The paper relies on this without support.
In the absence of adequate adipose tissue, combined with leptin deficiency, the liver becomes a major repository for triglycerides in lipodystrophic patients, often expanding far beyond the normal size.
“In the absence of adequate adipose tissue, combined with leptin deficiency, the liver becomes a major repository for triglycerides in lipodystrophic patients, often expanding far beyond the normal size.”
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
“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 [90]
In the citing paper
“The reduction of hepatomegaly was associated with improvement of nonalcoholic steatohepatitis, a severe inflammatory manifestation of NAFLD (12).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [12]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Baseline liver-fat mean does not match individual MRI values
MajorThe ten baseline liver-fat percentages in Table 1 average 57.1%, not the reported group mean of 31%. This changes a reported value used to describe the treatment effect.
Reported 31 · recomputed 57.1
“Liver fat by MRI (%) 31 Ϯ 7 1 1 Ϯ 6 .006”
Stated age range excludes a listed patient
MinorThe stated maximum age is 67 years, but Table 1 lists a patient aged 68.
“They ranged in age from 17 to 67 years.”
“Age/sex (y/M/F) 17/F 36/F 42/F 40/F 64/F 35/M 68/M”
Citations
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Leptin-Replacement Therapy for Lipodystrophy
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Self-citation
Flagged first, then by citations
2 of the 45 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Stern, J. H., Rutkowski, J. M., & Scherer, P. E. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.011 · Cited by 1,031
“accumulation and decrease the severity of NASH in lipodystrophic patients (Javor et al., 2005).”
BackgroundInsulin resistance: a metabolic pathway to chronic liver disease
Bugianesi, E., McCullough, A. J., & Marchesini, G. (2005) · Hepatology · doi:10.1002/hep.20920 · Cited by 900
The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome
Lim, J. S., Mietus-Snyder, M., Valente, A., Schwarz, J.-M., & Lustig, R. H. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.41 · Cited by 771
“For instance, patients with lipodystrophy are not obese, but have high levels of intrahepatic lipid”
BackgroundDuell, P. B., Welty, F. K., Miller, M., Chait, A., Hammond, G., Ahmad, Z., Cohen, D. E., Horton, J. D., Pressman, G. S., Toth, P. P., et al. (2022) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atv.0000000000000153 · Cited by 727
Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications
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“5%, improves hyperlipidemia (57, 58), and reverses hepatic steatosis (53, 54).”
BackgroundNon-alcoholic fatty liver disease: The mist gradually clears
de Alwis, N. M. W., & Day, C. P. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.01.009 · Cited by 605
“Features of PCOS (hyperandrogenism) should be sought in young women with suspected NAFLD [35] and clinical evidence of lipodystrophy should be sought in young, non-obese patients in view of its association with NAFLD [42].”
BackgroundLeptin in Human Physiology and Pathophysiology
Mantzoros, C. S., Magkos, F., Brinkoetter, M., Sienkiewicz, E., Dardeno, T. A., Kim, S.-Y., Hamnvik, O.-P. R., & Koniaris, A. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00315.2011 · Cited by 593
The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline
Brown, R. J., Araújo‐Vilar, D., Cheung, P. T., Dunger, D. B., Garg, A., Jack, M., Mungai, L., Oral, E. A., Patni, N., Rother, K. I., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2466 · Cited by 536
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“The liver weights of the curcumin-fed ob/ob mice did not weigh significantly less than controls, an effect potentially attributable to the complete absence of leptin in these mice, which has been shown be associated with severe and refractory hepatosteatosis (47, 48).”
BackgroundAdipokines in liver diseases #
Marra, F., & Bertolani, C. (2009) · Hepatology · doi:10.1002/hep.23046 · Cited by 468
Nonalcoholic fatty liver disease and the metabolic syndrome
Marchesini, G., Marzocchi, R., Agostini, F., & Bugianesi, E. (2005) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000174153.53683.f2 · Cited by 421
Obesity, Fat Mass and Immune System: Role for Leptin
Francisco, V., Pino, J., Campos-Cabaleiro, V., Ruiz-Fernández, C., Mera, A., Gonzalez-Gay, M. A., Gómez, R., & Gualillo, O. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00640 · Cited by 411
“Conversely, db/db mice presented an increased absolute number of B cells in the peritoneal cavity (Jennbacken et al., 2013), and the increase of leptin was correlated with a decrease in B cells of mice with unbalanced diets (carbohydraterich and fat-rich) (Martínez-Carrillo et al., 2015).”
BackgroundNonalcoholic Fatty Liver Disease: Pathologic Patterns and Biopsy Evaluation in Clinical Research
Kleiner, D. E., & Brunt, E. M. (2012) · Seminars in Liver Disease · doi:10.1055/s-0032-1306421 · Cited by 402
Self-citationPreclinical models of non-alcoholic fatty liver disease
Santhekadur, P. K., Kumar, D. P., & Sanyal, A. J. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.10.031 · Cited by 380
“However, ob/ob mice rarely develop NASH, which may be because of alterations in inflammatory responses and other effects.(49) Also, leptin deficiency requires an additional stimulus (LPS, HFD, MCD etc.”
Genetic Syndromes of Severe Insulin Resistance
Semple, R. K., Savage, D. B., Cochran, E. K., Görden, P., & O’Rahilly, S. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0020 · Cited by 367
Self-citationAdipokines in nonalcoholic fatty liver disease
Pοlyzos, S. A., Kountouras, J., & Mantzoros, C. S. (2015) · Metabolism · doi:10.1016/j.metabol.2015.11.006 · Cited by 369
Imajo, K., Fujita, K., Yoneda, M., Nozaki, Y., Ogawa, Y., Shinohara, Y., Kato, S., Mawatari, H., Shibata, W., Kitani, H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.05.012 · Cited by 341
“…increased serum leptin levels are generally associated with obesity, visceral fat accumulation, and steatosis (Considine et al., 1996; Halaas et al., 1995), and patients with NAFLD generally represent obesity and hyperleptinemia, except in atypical cases such as lipodystrophy (Javor et al., 2005).”
BackgroundAleffi, S., Petrai, I., Bertolani, C., Parola, M., Colombatto, S., Novo, E., Vizzutti, F., Anania, F. A., Milani, S., Rombouts, K., et al. (2005) · Hepatology · doi:10.1002/hep.20965 · Cited by 350
Leptin and the Central Nervous System Control of Glucose Metabolism
Morton, G. J., & Schwartz, M. W. (2011) · Physiological Reviews · doi:10.1152/physrev.00007.2010 · Cited by 338
“In humans, 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).”
BackgroundLeptin revisited: its mechanism of action and potential for treating diabetes
Coppari, R., & Bjørbæk, C. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3757 · Cited by 308
Non-alcoholic fatty liver disease pathogenesis: The present and the future
Petta, S., Muratore, C., & Craxı̀, A. (2009) · Digestive and Liver Disease · doi:10.1016/j.dld.2009.01.004 · Cited by 287
“compared to controls [118,137]”
BackgroundLeptin in human physiology and therapeutics
Dardeno, T. A., Chou, S. H.-H., Moon, H., Chamberland, J. P., Fiorenza, C. G., & Mantzoros, C. S. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.06.002 · Cited by 297
“Approximately 100 subjects have been studied in the context of small, uncontrolled interventional studies, which have shown that leptin replacement dramatically improves dyslipidemia and insulin sensitivity in these individuals and reduces glycosylated hemoglobin, hepatic gluconeogenesis, and hepatic fat content [172,…”
Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant and Diabetic Individuals
Moon, H., Dalamaga, Μ., Kim, S. Y., Pοlyzos, S. A., Hamnvik, O. R., Magkos, F., Paruthi, J., & Mantzoros, C. S. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1053 · Cited by 265
“6 months resulted in improvement of hepatic steatosis and ballooning but not portal inflammation or fibrosis (63).”
BackgroundLipodystrophy: pathophysiology and advances in treatment
Fiorenza, C. G., Chou, S. H.-H., & Mantzoros, C. S. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.199 · Cited by 255
Brain regulation of food intake and appetite: molecules and networks
Broberger, C. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2005.01553.x · Cited by 286
Leptin in nonalcoholic fatty liver disease: A narrative review
Polyzos, S. A., Kountouras, J., & Mantzoros, C. S. (2015) · Metabolism · doi:10.1016/j.metabol.2014.10.012 · Cited by 235
“For this reason, evidence could be indirectly derived from studies with patients with lipodystrophy and NAFLD [13,158-161], which are summarized in Table 4.”
Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy
Javor, E. D., Cochran, E. K., Musso, C., Young, J. R., DePaoli, A. M., & Gorden, P. (2005) · Diabetes · doi:10.2337/diabetes.54.7.1994 · Cited by 226
“The reduction of hepatomegaly was associated with improvement of nonalcoholic steatohepatitis, a severe inflammatory manifestation of NAFLD (12).”
BackgroundInfluentialSelf-citationLeptin treatment: Facts and expectations
Paz-Filho, G., Mastronardi, C. A., & Licinio, J. (2014) · Metabolism · doi:10.1016/j.metabol.2014.07.014 · Cited by 229
“It has been demonstrated that leptin improved NAFLD (nonalcoholic fatty liver disease) in lipodystrophic patients [83].”
BackgroundMaher, J. J., León, P., & Ryan, J. C. (2008) · Hepatology · doi:10.1002/hep.22399 · Cited by 208
Diagnosis and treatment of lipodystrophy: a step-by-step approach
Araújo-Vilar, D., & Santini, F. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-018-0887-z · Cited by 194
“Paired biopsy studies have shown that nonalcoholic steatohepatitis associated with GLD was ameliorated with metreleptin treatment [75, 76].”
Brain regulation of food intake and appetite: molecules and networks
Roberger, C. B. (2005) · Cited by 191
The Evolving Role of Leptin and Adiponectin in Chronic Liver Diseases
Tsochatzis, E. A., Papatheodoridis, G., & Archimandritis, A. J. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00848.x · Cited by 190
“In humans with severe lipodystrophy, recombinant leptin significantly reduced hepatic steatosis, triglycerides, transaminase activity, and NASH injury (19).”
BackgroundPediatric nonalcoholic fatty liver disease (NAFLD): A “growing” problem?
Roberts, E. A. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.03.003 · Cited by 177
“The lipodystrophies exhibit leptin deficiency, not leptin resistance, and effective treatment includes supplementation with leptin [36].”
BackgroundWhat lipodystrophies teach us about the metabolic syndrome
Mann, J. P., & Savage, D. B. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129190 · Cited by 185
Efficacy of leptin therapy in the different forms of human lipodystrophy
Chong, A. Y., Lupsa, B. C., Cochran, E. K., & Görden, P. (2009) · Diabetologia · doi:10.1007/s00125-009-1502-9 · Cited by 175
“Leptin has been used to treat other features of lipodystrophy, such as steatohepatitis [ 27 ] and polycystic ovary syndrome [28, 29].”
MethodSelf-citationParlati, L., Régnier, M., Guillou, H., & Postic, C. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100346 · Cited by 201
“However, when these mice are treated with lipopolysaccharide, or fed with a high-fat and MCD diet, they develop liver histological features of NASH without progressive liver fibrosis.(47) This model is therefore scarcely applicable to the study of NASH since: i) there is no progression towards extensive liver fibrosis…”
BackgroundPathophysiology of NASH: perspectives for a targeted treatment
Marra, F., & Lotersztajn, S. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113199990344 · Cited by 163
“NAFLD in lipodystrophic patients [72] .”
The liver diseases of lipodystrophy: The long-term effect of leptin treatment
Zadeh, E. S., Lungu, A. O., Cochran, E. K., Brown, R. J., Ghany, M. G., Heller, T., Kleiner, D. E., & Görden, P. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.02.007 · Cited by 169
“We previously reported a preliminary study of the effect of recombinant human methionyl leptin (metreleptin, Amylin Pharmaceuticals, San Diego, CA) therapy in the treatment of NAFLD in lipodystrophy [5].”
BackgroundResultSelf-citationLee, J. H., Chan, J. L., Sourlas, E., Raptopoulos, V., & Mantzoros, C. S. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1545 · Cited by 163
Progress and challenges in the prevention and control of nonalcoholic fatty liver disease
Cai, J., Zhang, X., & Li, H. (2018) · Medicinal Research Reviews · doi:10.1002/med.21515 · Cited by 161
Insulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat?
Larter, C. Z., & Farrell, G. C. (2005) · Journal of Hepatology · doi:10.1016/j.jhep.2005.11.030 · Cited by 155
Adipocytokines and liver disease
Kamada, Y., Takehara, T., & Hayashi, N. (2008) · Journal of Gastroenterology · doi:10.1007/s00535-008-2213-6 · Cited by 155
“Patients with severe lipodystrophy present with hepatic steatosis and hepatocellular ballooning injury, similar to that seen in NASH, and recombinant leptin signifi cantly reduces serum levels of triglycerides, transaminases, and liver fat content and improves hepatomegaly in these patients.(46) Leptin injections in m…”
BackgroundClinical Effects of Long-Term Metreleptin Treatment in Patients With Lipodystrophy
Chan, J. L., Lutz, K., Cochran, E. K., Huang, W., Peters, Y., Weyer, C., & Görden, P. (2011) · Endocrine Practice · doi:10.4158/ep11229.or · Cited by 147
“Effect of Metreleptin Treatment on Hepatic Enzymes Hepatic steatosis, hepatomegaly, and nonalcoholic steatohepatitis are commonly observed in patients with lipodystrophy (15).”
Self-citation‘Endocrine NAFLD’ a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis
Lonardo, A., Carani, C., Carulli, N., & Loria, P. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.03.005 · Cited by 145
“In patients with severe lipodystrophy, leptin administration reduces liver enzymes, volume [164–166], fat content [167] and histological features of steatohepatitis but not fibrosis [168].”
BackgroundMechanisms of intrahepatic triglyceride accumulation
Ress, C. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i4.1664 · Cited by 135
Therapeutic potential of green tea in nonalcoholic fatty liver disease
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Ten years of leptin replacement therapy
Paz-Filho, G., Wong, M., & Licinio, J. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2010.00840.x · Cited by 130
“Furthermore, leptin can be a potential anti-lipotoxic agent in a clinical setting, such as for preventing transplanted islet cell graft failure (45) and for treating non-alcoholic steatohepatitis (46).”
BackgroundLipodystrophy Due to Adipose Tissue–Specific Insulin Receptor Knockout Results in Progressive NAFLD
Softic, S., Boucher, J., Solheim, M. H., Fujisaka, S., Haering, M.-F., Homan, E. P., Winnay, J. N., Pérez‐Atayde, A. R., & Kahn, C. R. (2016) · Diabetes · doi:10.2337/db16-0213 · Cited by 128
“The most characteristic feature of fatty liver disease associated with lipodystrophy is prominent steatosis with hepatocyte balloon degeneration (8,15), pointing to lipotoxicity as an important pathway of liver injury.”
O’Regan, D. P., Callaghan, M. F., Wylezinska, M., Fitzpatrick, J. A., Naoumova, R. P., Hajnal, J. V., & Schmitz, S. A. (2008) · Radiology · doi:10.1148/radiol.2472070880 · Cited by 122
Lipodystrophy: lessons in lipid and energy metabolism
Simha, V., & Garg, A. (2006) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000217898.52197.18 · Cited by 115
Pοlyzos, S. A., Perakakis, N., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2019.05.001 · Cited by 117
Role of leptin resistance in the development of obesity in older patients
Picard, F., Carter, S., Caron, A., & Richard, D. (2013) · Clinical Interventions in Aging · doi:10.2147/cia.s36367 · Cited by 134
“However, in leptin-deficient lipodystrophic patients suffering from nonalcoholic fatty liver disease (NAFLD), administration of leptin improved their condition dramatically.(76) Taken together, these data suggest that the positive effects of leptin on triglycerides oxidation in the liver may overcome the effects of st…”
Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases
Martinez‐Uña, M., López‐Mancheño, Y., Diéguez, C., Fernandez-Rojo, M. A., & Novelle, M. G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249368 · Cited by 120
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“There are metabolic abnormalities such as NASH that improve with leptin treatment in lipodystrophy patients [11,12].”
BackgroundSelf-citationLipodystrophies, dyslipidaemias and atherosclerotic cardiovascular disease
Hussain, I., Patni, N., & Garg, A. (2018) · Pathology · doi:10.1016/j.pathol.2018.11.004 · Cited by 105
Pediatric NAFLD: an overview and recent developments in diagnostics and treatment
Draijer, L. G., Benninga, M. A., & Koot, B. G. P. (2019) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2019.1595589 · Cited by 106
“Experimental therapies Anti-LPS antibody [168] Monoclonal antibody, reduces delivery of lipopolysaccharide from the gut to the liver Improvement of insulin sensitivity, small effect on liver enzymes Phase 2”
BackgroundAdiponectin and leptin in the diagnosis and therapy of NAFLD
Boutari, C., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2019.154028 · Cited by 100
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
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“(4) have shown metreleptin-induced improvement in both steatosis and histological scores of steatohepatitis in 10 patients with severe lipodystrophy; two of these patients had FPLD, and one of them showed a reduction in hepatic fat as measured by magnetic resonance imaging (4).”
BackgroundShpakov, A. O., Derkach, K. V., & Berstein, L. M. (2015) · Future Science OA · doi:10.4155/fso.15.23 · Cited by 93
Lutchman, G. A., Promrat, K., Kleiner, D. E., Heller, T., Ghany, M. G., Yanovski, J. A., Liang, T. J., & Hoofnagle, J. H. (2006) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2006.05.005 · Cited by 90
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20 YEARS OF LEPTIN: Leptin in common obesity and associated disorders of metabolism
DePaoli, A. M. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0258 · Cited by 86
“Fibrosis was unchanged over this short interval (Javor et al. 2005).”
Self-citationRoubíček, 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].”
Perspectives on Treatment for Nonalcoholic Steatohepatitis
Lassailly, G., Caiazzo, R. J., Pattou, F. N., & Mathurin, P. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.03.004 · Cited by 87
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Rationale for Leptin-Replacement Therapy for Severe Lipodystrophy
Oral, E. A., & Chan, J. L. (2010) · Endocrine Practice · doi:10.4158/ep09155.ra · Cited by 77
Self-citationMeehan, 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
“NASH, which is a fibrosing condition of the liver, may actually be improved by metreleptin therapy.[7,8] A third example is inflammatory conditions in the central nervous system of rodents that occur in the presence of leptin but not in its absence.”
BackgroundSelf-citationNew Pharmacological Perspectives for the Leptin Receptor in the Treatment of Obesity
Roujeau, C., Jockers, R., & Dam, J. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00167 · Cited by 71
Resistance to leptin action is the major determinant of hepatic triglyceride accumulation in vivo
Fishman, S., Muzumdar, R. H., Atzmon, G., Ma, X., Yang, X., Einstein, F. H., & Barzilai, N. (2006) · The FASEB Journal · doi:10.1096/fj.06-6557com · Cited by 70
“hepatic TG (10, 19) through the regulation of fat and”
BackgroundNonalcoholic Fatty Liver Disease
Paredes, A. H., Torres, D. M., & Harrison, S. A. (2012) · Clinics in Liver Disease · doi:10.1016/j.cld.2012.03.005 · Cited by 72
Adipokines that link obesity and diabetes to the hypothalamus
Ahima, R. S., Qi, Y., & Singhal, N. S. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53009-2 · Cited by 72
Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer
Rajesh, Y., & Sarkar, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042163 · Cited by 75
“Likewise, recombinant leptin and metreleptin (leptin analog), administered for lipodystrophy and congenital leptin deficiency, have been reported to reverse hepatic lipid accumulation and reduce the consequences of NASH [53].”
BackgroundInherited lipodystrophies and hypertriglyceridemia.
Simha, V., & Garg, A. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32832d4a33 · Cited by 67
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
Non-alcoholic Steatohepatitis in Children
Roberts, E. A. (2007) · Clinics in Liver Disease · doi:10.1016/j.cld.2007.02.008 · Cited by 64
Effects 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
“Patients with lipodystrophy typically have NAFLD before leptin replacement, and those with AGL may have concomitant autoimmune hepatitis (14, 26).”
BackgroundSelf-citationRetinoids ameliorate insulin resistance in a leptin-dependent manner in mice
Tsuchiya, H., Ikeda, Y., Ebata, Y., Kojima, C., Katsuma, R., Tsuruyama, T., Sakabe, T., Shomori, K., Komeda, N., Oshiro, S., et al. (2012) · Hepatology · doi:10.1002/hep.25798 · Cited by 65
“Moreover, genetic leptin deficiency as occurs in ob/ob mice and in patients with lipodystrophy results in severe insulin resistance, which can be reversed by leptin replacement therapy.(7,8) These results suggest that insulin resistance may be a consequence of leptin resistance.”
BackgroundLeptin in Health and Disease: Facts and Expectations at its Twentieth Anniversary
Pοlyzos, S. A., & Mantzoros, C. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.10.017 · Cited by 67
“[83] Javor ED, Ghany MG, Cochran EK, Oral EA, DePaoli AM, Premkumar A, et al.”
BackgroundAdipose tissue as source and target for novel therapies
Klein, J. C., Perwitz, N., Kraus, D., & Faßhauer, M. (2005) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2005.11.008 · Cited by 63
Non-Alcoholic Fatty Liver Disease: Is Bariatric Surgery the Answer?
Pillai, A. A., & Rinella, M. E. (2009) · Clinics in Liver Disease · doi:10.1016/j.cld.2009.07.012 · 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
“[103,109] Hepatocellular injuries and transaminases that are linked to non-alcoholic steatohepatitis (NASH)may also be reduced but this is a point that needs to be studied further.”
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
“50 However, clinical studies with leptin therapy for 4 to 18 months improved the NASH (nonalcoholic steatohepatitis) score without affecting the fibrosis score in liver biopsy.(35) It should be emphasized that leptin administration in the present study was performed on the basis of the pathophysiologic condition of hy…”
BackgroundSpectrum of Renal Diseases Associated with Extreme Forms of Insulin Resistance
Musso, C., Javor, E. D., Cochran, E. K., Balow, J. E., & Görden, P. (2006) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.01271005 · Cited by 56
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“Other factors could have also contributed to steatosis in HFD animals, such as leptin deficiency and/or resistance [41,42].”
BackgroundChan, D. C., Watts, G. F., Ng, T., Hua, J., Song, S. E., & Barrett, P. H. R. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2005.00543.x · Cited by 53
The Multifaceted Associations of Hepatobiliary Disease and Diabetes
Bell, D. S. H., & Allbright, E. (2007) · Endocrine Practice · doi:10.4158/ep.13.3.300 · Cited by 51
Diagnostic strategies and clinical management of lipodystrophy
Foss‐Freitas, M. C., Akıncı, B., Luo, Y., Stratton, A., & Oral, E. A. (2020) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2020.1735360 · Cited by 53
“Briefly, metreleptin therapy improves hyperphagia in patients with GL, reduces triglycerides and HbA1c, improves insulin sensitivity, ameliorates hepatic steatosis, and reduces liver enzymes and the liver volume [198,200,204,205].”
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“Furthermore, leptin treatment prominently reduced hepatic triglyceride accumulation [4] and improved type II diabetes in clinical patients [5], clearly indicating a protective role of leptin against obesity and diabetes.”
BackgroundMASLD in children: integrating epidemiological trends with mechanistic and translational advances
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“resistance in patients with severe lipodystrophy (4, 6, 7), it is not effective in reversing these conditions in patients with partial lipodystrophy (8).”
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“In humans, congenital lipodystrophies are associated with partial or total LEP deficiency, and LEP replacement dramatically improves IS and removes intrahepatic fat content [41,42].”
Background
Metadata
- Authors
- Javor, E. D., Ghany, M. G., Cochran, E. K., Oral, E. A., DePaoli, A. M., Premkumar, A., Kleiner, D. E., & Gorden, P.
- Affiliations
- National Institutes of Health (US)
- Amgen (United States) (US)
- Corresponding author
- Javor, Edward D.
- Venue
- Hepatology
- Published
- 2005-04
- Volume
- 41
- Issue
- 4
- Pages
- 753-760
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2064309380
- Semantic Scholar
- ed56502ccbe96c2f2b6ef8670f3ba0436824e56d
- Cited by
- 228
- References
- 45
- Citations by year
- 2025: 10 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 12 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 9 · 2016: 7 · 2015: 12 · 2014: 19 · 2013: 14 · 2012: 16
- FWCI
- 11.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- nonalcoholic steatohepatitis, generalized lipodystrophy, hepatic steatosis, hepatocyte ballooning, liver fibrosis, serum triglycerides, transaminases, liver fat, hepatomegaly, hypoleptinemia
- MeSH terms
- Adolescent, Adult, Aged, Transaminases, Fatty Liver, Female, Hepatitis, Humans, Lipodystrophy, Liver, Magnetic Resonance Imaging, Male, Middle Aged, Pilot Projects, Triglycerides, Hormone Replacement Therapy, 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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