A novel aminosterol reverses diabetes and fatty liver disease in obese mice

Nobuhiko Takahashi, Yong Qi, Hiral R. Patel, Rexford S. Ahima

Research output: Contribution to journalArticle

Abstract

Background/Aims Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight reduction alone does not prevent the development or progression of NAFLD. Since NAFLD is associated with insulin resistance and diabetes, we hypothesized that improvement of these factors would reverse obesity-related NAFLD. Methods We examined the effects of an aminosterol, 1436, on glucose, lipids and liver metabolism in Lepob/ob mice, a model of obesity, severe insulin resistance, diabetes, hyperlipidemia and hepatic steatosis. Results 1436 decreased body weight, specifically fat content, by inhibiting food intake and increasing energy expenditure. In contrast to weight loss from food restriction, this aminosterol specifically lowered circulating lipids, reversed hepatic steatosis and normalized alanine aminotransferase level. 1436 decreased glucose, increased adiponectin and enhanced insulin action in liver. These changes culminated in inhibition of hepatic triglyceride synthesis and increased fatty acid oxidation. Gene expression studies confirmed a reduction in lipogenic enzymes in liver, and elevation of enzymes involved in lipid catabolism. Conclusions These results demonstrate that 1436 is an effective treatment for insulin resistance and hepatic steatosis in Lep ob/ob mice, by decreasing hepatic lipid synthesis and stimulating lipolysis. In contrast, weight loss from food restriction has no substantial effect on insulin resistance, lipids and hepatic steatosis.

Original languageEnglish (US)
Pages (from-to)391-398
Number of pages8
JournalJournal of Hepatology
Volume41
Issue number3
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

Keywords

  • ACOx, acylCoA oxidase
  • Adiponectin
  • Aminosterol
  • CPT, carnitine palmitoyltransferase
  • Diabetes
  • FAS, fatty acid synthase
  • GPAT, glycerol-3-phosphate acyltransferase
  • Non-alcoholic fatty liver
  • Obesity
  • SREBP, sterol regulatory element-binding protein

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'A novel aminosterol reverses diabetes and fatty liver disease in obese mice'. Together they form a unique fingerprint.

  • Cite this