Abstract | BACKGROUND/AIMS: METHODS: 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.
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Authors | Nobuhiko Takahashi, Yong Qi, Hiral R Patel, Rexford S Ahima |
Journal | Journal of hepatology
(J Hepatol)
Vol. 41
Issue 3
Pg. 391-8
(Sep 2004)
ISSN: 0168-8278 [Print] Netherlands |
PMID | 15336441
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cholestanols
- RNA, Messenger
- aminosterol 1436
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Topics |
- Animals
- Base Sequence
- Body Weight
(drug effects)
- Cholestanols
(therapeutic use)
- Diabetes Complications
(drug therapy, genetics, metabolism)
- Fatty Liver
(complications, drug therapy, genetics, metabolism)
- Female
- Gene Expression
(drug effects)
- Lipid Metabolism
- Liver
(drug effects, pathology)
- Mice
- Mice, Inbred C57BL
- Mice, Obese
- Obesity
(complications, drug therapy, genetics, metabolism)
- Organ Size
(drug effects)
- RNA, Messenger
(genetics, metabolism)
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