Liver Peroxisome Proliferator-activated Receptor γ Contributes to Hepatic Steatosis, Triglyceride Clearance, and Regulation of Body Fat Mass*

By O. Gavrilova, M. Haluzík, K. Matsusue, Jaime J. Cutson, L. Johnson, Kelly R. Dietz, C. Nicol, C. Vinson, F. Gonzalez, M. Reitman. Journal of Biological Chemistry, 2003

770 citations recorded by the source corpus.

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that mediates the antidiabetic effects of thiazolidinediones. PPARγ is present in adipose tissue and becomes elevated in fatty livers, but the roles of specific tissues in thiazolidinedione actions are unclear. We studied the function of liver PPARγ in both lipoatrophic A-ZIP/F-1 (AZIP) and wild type mice. In AZIP mice, ablation of liver PPARγ reduced the hepatic steatosis but worsened the hyperlipidemia, triglyceride clearance, and muscle insulin resistance. Inactivation of AZIP liver PPARγ also abolished the hypoglycemic and hypolipidemic effects of rosiglitazone, demonstrating that, in the absence of adipose tissue, the liver is a primary and major site of thiazolidinedione action. In contrast, rosiglitazone remained effective in non-lipoatrophic mice lacking liver PPARγ, suggesting that adipose tissue is the major site of thiazolidinedione action in typical mice with adipose tissue. Interestingly, mice without liver PPARγ, but with adipose tissue, developed relative fat intolerance, increased adiposity, hyperlipidemia, and insulin resistance. Thus, liver PPARγ regulates triglyceride homeostasis, contributing to hepatic steatosis, but protecting other tissues from triglyceride accumulation and insulin resistance.

Subfields: Epidemiology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/e60bbf8d6f9dfd95067d10789ed0d122ff186ee7

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In Epidemiology

1. Bruce E. Kemp
2. G. Steinberg
3. Liangyou Rui

In Molecular Biology

1. B. Torstensen
2. G. Steinberg
3. A. Jordal
4. Bruce E. Kemp
5. T. Mak
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In Physiology

1. B. Torstensen
2. Bruce E. Kemp
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4. G. Steinberg
5. Liangyou Rui
6. D. Tocher

Citations in the corpus

• Complete replacement of dietary fish oil with a vegetable oil blend affect liver lipid and plasma lipoprotein levels in Atlantic salmon (Salmo salar L.) (2007, background): “Recent studies performed in knock out mice suggest a role for liver PPARγ2 in lipid homeostasis as an important regulator of genes involved in lipogenesis, and fatty acid storage, but also fatty acid transport and oxidation (Gavrilova et al., 2003; Wolf, 2004).”
• Molecular mediators of hepatic steatosis and liver injury. (2004, neutral): “The genetic deletion of hepatic PPAR-γ in livers of either ob/ob (44) or AZIP-F-1 (45) mice markedly attenuates the development of hepatic steatosis, independent of the presence of hyperinsulinemia or hyperglycemia.”
• AMPK in Health and Disease. (2009, methodology): “The mammalian AMPK domain limits were established experimentally by partial proteolysis (395), and a stable rat 1(68-163) fragment was expressed and crystallized in the presence of -cyclodextrin (an 1-4 linked heptaglucan), as had previously been performed for other starch binding domain structural ”
• Integrated physiology and systems biology of PPARα (2014, neutral): “[142] Gavrilova, O.”
• Energy Metabolism in the Liver (2014, positive): “The levels PPAR γ in the liver are low in normal mice and increase in mice with obesity (65, 167, 178).”
• Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. (2004, background): “steatosis (in A-ZIP transgenic background), and reduced insulin sensitivity (36, 37).”