Cholate inhibits high-fat diet-induced hyperglycemia and obesity with acyl-coa synthetase mrna decrease. Ikemoto, Shinji, Mayumi Takahashi, Nobuyo Tsunoda, Kayo Maruyama, Hiroshige Itakura, Kentaro Kawanaka, Izumi Tabata, Mitsuru Higuchi, Tsuyoshi Tange, Tokuo T. Yamamoto, and Osamu Ezaki. Division of Clinical Nutrition and Health Promotion, National Institute of Health and Nutrition, Toyama, Tokyo 162, Japan, Department of Pathology, Faculty of Medicine, University of Tokyo, Tokyo 113, Japan, Tohoku University Gene Research Center, Sendai 981, Japan
APStracts 4:0064E, 1997.
The effects of sodium cholate on high-fat diet-induced hyperglycemia and obesity were investigated. Insulin resistance was estimated by measuring 2-deoxy glucose uptake in epitrochlearis muscles incubated in vitro. Addition of 0.5% cholate to high-safflower oil diet completely prevented high fat-induced hyperglycemia and obesity in C57BL/6J mice with a slight decrease of energy intake but with no inhibition of fat absorption. Furthermore, the addition of cholate decreased blood insulin levels and prevented high-fat diet-induced decrease of glucose uptake in epitrochlearis. However, there was no change in the unsaturation index of fatty acids in skeletal muscles and in GLUT4 levels by cholate. In liver, cholate addition resulted in cholesterol accumulation and completely prevented high-fat diet -induced triglyceride accumulation. The changes of triglyceride level in liver were paralleled to the changes of acyl-CoA synthetase (ACS) mRNA. ACS catalyses the formation of acyl-CoA from fatty acid, and acyl-CoA is utilized for triglyceride formation in liver. ACS has a sterol responsive element 1 (SRE-1) in its promoter region. These data indicate that the favorable effects of cholate could be partly the result of down regulation of ACS mRNA.

Received 23 October 1996; accepted in final form 20 February
1997.
APS Manuscript Number E528-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 21 March 1997