ArticleJCI insight2020
Leptin decreases de novo lipogenesis in patients with lipodystrophy.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Selective targeting of angiopoietin-like 3 (ANGPTL3) with vupanorsen for the treatment of patients with familial partial lipodystrophy (FPLD): results of a proof-of-concept study.Lipids in health and disease · 2021Trial
- Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2021Trial
- Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings.Med (New York, N.Y.) · 2021Trial
- Research Progress on Leptin in Metabolic Dysfunction-associated Fatty Liver Disease.Journal of clinical and translational hepatology · 2025Review
- Leptin and leptin resistance in obesity: current evidence, mechanisms and future directions.Endocrine connections · 2025Review
- Influence of diet and body weight in treatment-resistant acquired partial lipodystrophy after hematopoietic stem cell transplantation and its potential for metabolic improvement.Diabetology international · 2024Article
- Review
- Leptin Decreases Gluconeogenesis and Gluconeogenic Substrate Availability in Patients With Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2023Article
- Isotope Labeling and Biochemical Assessment of Liver-Triacylglycerol in Patients with Different Levels of Histologically-Graded Liver Disease.The Journal of nutrition · 2023Article
- Liver insulinization as a driver of triglyceride dysmetabolism.Nature metabolism · 2023Review
- Non-Alcoholic Fatty Liver Disease: Translating Disease Mechanisms into Therapeutics Using Animal Models.International journal of molecular sciences · 2023Review
- Associations of fatty acids composition and estimated desaturase activities in erythrocyte phospholipids with biochemical and clinical indicators of cardiometabolic risk in non-diabetic Serbian women: the role of level of adiposity.Frontiers in nutrition · 2023Article
- Excess 11-Oxygenated Androgens in Women With Severe Insulin Resistance Are Mediated by Adrenal Insulin Receptor Signaling.The Journal of clinical endocrinology and metabolism · 2022Article
- Treatment Options for Lipodystrophy in Children.Frontiers in endocrinology · 2022Review
- Abnormal transaminase and lipid profiles in coexisting diseases in patients with fatty liver: a population study in Sichuan.Bioscience reports · 2021Article
- From leptin to lasers: the past and present of mouse models of obesity.Expert opinion on drug discovery · 2021Article
- Apolipoprotein CIII and Angiopoietin-like Protein 8 are Elevated in Lipodystrophy and Decrease after Metreleptin.Journal of the Endocrine Society · 2021Article
- Tissue-Specific Effects of Leptin on Glucose and Lipid Metabolism.Endocrine reviews · 2021Review
- Molecular and Cellular Bases of Lipodystrophy Syndromes.Frontiers in endocrinology · 2021Review
- Neuropeptide Y and Metabolism Syndrome: An Update on Perspectives of Clinical Therapeutic Intervention Strategies.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
De novo lipogenesis (DNL) plays a role in the development of hepatic steatosis. In humans with lipodystrophy, reduced adipose tissue causes lower plasma leptin, insulin resistance, dyslipidemia, and ectopic triglyceride (TG) accumulation. We hypothesized that recombinant leptin (metreleptin) for 6 months in 11 patients with lipodystrophy would reduce DNL by decreasing insulin resistance and glycemia, thus reducing circulating TG and hepatic TG. The percentage of TG in TG-rich lipoprotein particle (TRLP-TG) derived from DNL (%DNL) was measured by deuterium incorporation from body water into palmitate. At baseline, DNL was elevated, similar to levels previously shown in obesity-associated nonalcoholic fatty liver disease (NAFLD). After metreleptin, DNL decreased into the normal range. Similarly, absolute DNL (TRLP-TG × %DNL) decreased by 88% to near-normal levels. Metreleptin improved peripheral insulin sensitivity (hyperinsulinemic-euglycemic clamp) and lowered hemoglobin A1c and hepatic TG. Both before and after metreleptin, DNL positively correlated with insulin resistance, insulin doses, and hepatic TG, supporting the hypothesis that hyperinsulinemia stimulates DNL and that elevated DNL is integral to the pathogenesis of lipodystrophy-associated NAFLD. These data suggest that leptin-mediated improvement in insulin sensitivity increases clearance of blood glucose by peripheral tissues, reduces hepatic carbohydrate flux, and lowers insulinemia, resulting in DNL reductions and improvements in hepatic steatosis and dyslipidemia.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.