Site and mechanism of leptin action in a rodent form of congenital lipodystrophy

Asilmaz, Esra; Cohen, Paul; Miyazaki, Masaru; Dobrzyń, Paweł; Ueki, Kohjiro; Fayzikhodjaeva, Gulnorakhon; Soukas, Alexander A.; Kahn, C. Ronald; Ntambi, James M.; Socci, Nicholas D.; Friedman, Jeffrey M.

doi:10.1172/jci19511

Cited by 89 publications

(60 citation statements)

References 55 publications

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“…PPAR␣, which belongs to the superfamily of ligand-activated nuclear hormone receptor, is involved in lipid metabolism by regulating the transcription of some genes that participate in peroxisomal, microsomal, and mitochondrial fatty acid oxidation, as well as hepatic lipid transporters (Hashimoto et al, 1999;Minokoshi et al, 2002;Kok et al, 2003;Asilmaz et al, 2004). Some investigators have shown that PPAR␣ agonists prevent and/or improve hepatic steatosis in animal models of NAFLD (Chou et al, 2002;Ip et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Preventive effects of total flavonoids of Litsea coreana leve on hepatic steatosis in rats fed with high fat diet

Wang

Zou

et al. 2009

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 99%

Preventive effects of total flavonoids of Litsea coreana leve on hepatic steatosis in rats fed with high fat diet

Wang

Zou

et al. 2009

Journal of Ethnopharmacology

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“…Leptin administration markedly improved the metabolic defects of lipodystrophic mice, indicating that these defects were not due to an absence of TAG storage depots but to the absence of an adipose-derived factor [102]. Interestingly, central leptin repressed SCD-1 mRNA and enzymatic activity in lipodystrophic mice, indicating that the effects of leptin on liver SCD-1 are likely mediated by central action [103]. This is in line with the recent finding that central administration of recombinant leptin reverses diet-induced hepatic insulin resistance mainly by decreasing glycogenolysis [104].…”

Section: Role Of Leptin and Adiponectinmentioning

confidence: 95%

Regulation of fat metabolism in the liver: link to non-alcoholic hepatic steatosis and impact of physical exercise

Lavoie

Gauthier

2006

Cell. Mol. Life Sci.

131

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Hepatic steatosis may develop as a consequence of several dysfunctions. An increased circulating non-esterified fatty acid (NEFA) pool seems to be a major determinant in the pathogenesis of non-alcoholic fatty liver disease. Increased activation of the transcription factor sterol-regulatory-element-binding protein-1c, which promotes fatty acid synthesis, also contributes to hepatic fat accumulation. Increased hepatic fat oxidation with hepatic steatosis may be triggered by increased hepatic fat concentrations through the action of hepatic peroxisomes mediated by peroxisome proliferator-activated receptor alpha. Finally, inhibition in very low density lipoprotein secretion may also result in hepatic steatosis. This appears to be mainly controlled by the esterification of NEFAs into triacylglycerols by diacyglycerol acyltransferase-1 and -2 and the microsomal transfer protein. Physical exercise would interfere with the development of hepatic steatosis by stimulating lipid oxidation and inhibiting lipid synthesis in liver through the activation of the AMP-activated protein kinase pathway.

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“…In mouse models of generalized lipodystrophy, leptin infusion markedly decreases exaggerated hepatic lipogenesis [8,44], possibly by decreasing the transcriptional activity of carbohydrate responsive element binding protein (ChREBP) [8], a master regulator of hepatic de novo lipogenesis. Notably, leptin actions on both insulin resistance and hepatic lipogenesis depend exclusively on the actions of this hormone on the CNS [3]. Activation of 5′-AMP-activated protein kinase (AMPK) in muscle and liver may underlie the beneficial effects of leptin in lipid metabolism by increasing fatty acid oxidation and, thus, lowering lipid accumulation in these specific tissues [30,33].…”

Section: Metabolic Therapy With Recombinant Leptinmentioning

confidence: 99%

Lipodystrophies: adipose tissue disorders with severe metabolic implications

Cortés

Fernández‐Galilea

2015

J Physiol Biochem

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Lipodystrophy encompass a group of heterogeneous disorders consisting in marked reduction, absence, and/or the redistribution of adipose tissue. Lipodystrophy is frequently complicated with severe insulin resistance, diabetes, hyperlipidemia, and fatty liver. Anatomically, lipodystrophies can be partial or generalized. Etiologically, they can be congenital or acquired. Lipodystrophy diagnosis can be challenging, and it has been suggested that partial forms can be easily misdiagnosed as common central obesity with associated metabolic syndrome. Conventional insulin-sensitizing approaches usually fail to fully ameliorate insulin resistance in lipodystrophic patients. Leptin replacement is an approved therapy for the metabolic complications of congenital generalized lipodystrophy. Novel nutritional interventions are promising complementary approaches for treating lipodystrophy metabolic complications.

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Site and mechanism of leptin action in a rodent form of congenital lipodystrophy

Cited by 89 publications

References 55 publications

Preventive effects of total flavonoids of Litsea coreana leve on hepatic steatosis in rats fed with high fat diet

Preventive effects of total flavonoids of Litsea coreana leve on hepatic steatosis in rats fed with high fat diet

Regulation of fat metabolism in the liver: link to non-alcoholic hepatic steatosis and impact of physical exercise

Lipodystrophies: adipose tissue disorders with severe metabolic implications

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