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Author Notes:

Address for reprint requests and other correspondence: F. A. Anania, Division of Digestive Diseases, Emory Univ. School of Medicine, 615 Michael St., Suite 201, Rm. 248, Lab 255 Whitehead Biomedical Research Bldg., Atlanta, GA 30322 (e-mail: fanania@emory.edu).

Subject:

Research Funding:

This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R24 DK064399, RO1 DK062092, and RO1 DK 075397 and by National Science Foundation Award no. 0450303 (I-66-606-63).

Keywords:

  • fatty acid binding protein
  • fatty acids
  • microsomal triglyceride transfer protein

Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet

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Journal Title:

AJP - Gastrointestinal and Liver Physiology

Volume:

Volume 302, Number 2

Publisher:

, Pages G225-G235

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The aims of this study were designed to determine whether liraglutide, a long-acting glucagon-like peptide, could reverse the adverse effects of a diet high in fat that also contained trans-fat and high-fructose corn syrup (ALIOS diet). Specifically, we examined whether treatment with liraglutide could reduce hepatic insulin resistance and steatosis as well as improve cardiac function. Male C57BL/6J mice were pair fed or fed ad libitum either standard chow or the ALIOS diet. After 8 wk the mice were further subdivided and received daily injections of either liraglutide or saline for 4 wk. Hyperinsulinemic-euglycemic clamp studies were performed after 6 wk, revealing hepatic insulin resistance. Glucose tolerance and insulin resistance tests were performed at 8 and 12 wk prior to and following liraglutide treatment. Liver pathology, cardiac measurements, blood chemistry, and RNA and protein analyses were performed. Clamp studies revealed hepatic insulin resistance after 6 wk of ALIOS diet. Liraglutide reduced visceral adiposity and liver weight (P < 0.001). As expected, liraglutide improved glucose and insulin tolerance. Liraglutide improved hypertension (P < 0.05) and reduced cardiac hypertrophy. Surprisingly, liver from liraglutide-treated mice had significantly higher levels of fatty acid binding protein, acyl-CoA oxidase II, very long-chain acyl-CoA dehydrogenase, and microsomal triglyceride transfer protein. We conclude that liraglutide reduces the harmful effects of an ALIOS diet by improving insulin sensitivity and by reducing lipid accumulation in liver through multiple mechanisms including, transport, and increase β-oxidation.

Copyright information:

Copyright © 2012 the American Physiological Society

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