Cholate inhibits high-fat diet-induced hyperglycemia and obesity with acyl-CoA synthetase mRNA decrease

• Published in: The American journal of physiology Vol. 273; no. 1; pp. E37 - E45
• Main Authors: Ikemoto, S, Takahashi, M, Tsunoda, N, Maruyama, K, Itakura, H, Kawanaka, K, Tabata, I, Higuchi, M, Tange, T, Yamamoto, T.T
• Format: Journal Article
• Language: English
• Published: United States 01.07.1997
• Subjects: Analysis of Variance; Animals; Cholesterol - metabolism; Cholic Acid; Cholic Acids - pharmacology; Coenzyme A Ligases - biosynthesis; diet-related diseases; Dietary Fats - analysis; Energy Intake; Fatty Acids - analysis; Fatty Acids - chemistry; Fatty Acids, Nonesterified - metabolism; Feces - chemistry; Female; Gene Expression Regulation, Enzymologic - drug effects; Glucose Transporter Type 4; human nutrition; Hyperglycemia - etiology; Hyperglycemia - prevention & control; Liver - drug effects; Liver - metabolism; Mice; Mice, Inbred C57BL; Monosaccharide Transport Proteins - metabolism; Muscle Proteins; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; nutrition physiology; Obesity - enzymology; Obesity - etiology; Obesity - prevention & control; Phospholipids - chemistry; Repressor Proteins; RNA, Messenger - biosynthesis; Saccharomyces cerevisiae Proteins; Transcription, Genetic - drug effects; Triglycerides - metabolism
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpendo.1997.273.1.e37

The effects of sodium cholate on high-fat diet-induced hyperglycemia and obesity were investigated. Insulin resistance was estimated by measuring 2-deoxyglucose 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 GLUT-4 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 the liver were paralleled to the changes of acyl-CoA synthetase (ACS) mRNA. ACS catalyzes 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 in its promoter region. These data indicate that the favorable effects of cholate could be partly the result of downregulation of ACS mRNA.