Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Cholesterol / metabolism
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Cholic Acid
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Cholic Acids / pharmacology*
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Coenzyme A Ligases / biosynthesis*
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Dietary Fats* / analysis
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Energy Intake
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Fatty Acids / analysis
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Fatty Acids / chemistry
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Fatty Acids, Nonesterified / metabolism
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Feces / chemistry
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Female
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Gene Expression Regulation, Enzymologic / drug effects
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Glucose Transporter Type 4
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Hyperglycemia / etiology
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Hyperglycemia / prevention & control*
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Liver / drug effects
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Liver / metabolism
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Mice
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Mice, Inbred C57BL
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Monosaccharide Transport Proteins / metabolism
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Muscle Proteins*
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / metabolism
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Obesity / enzymology
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Obesity / etiology
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Obesity / prevention & control*
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Phospholipids / chemistry
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RNA, Messenger / biosynthesis*
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Repressor Proteins*
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Saccharomyces cerevisiae Proteins*
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Transcription, Genetic / drug effects*
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Triglycerides / metabolism
Substances
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Cholic Acids
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Dietary Fats
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Fatty Acids
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Fatty Acids, Nonesterified
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Glucose Transporter Type 4
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Monosaccharide Transport Proteins
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Muscle Proteins
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Phospholipids
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RNA, Messenger
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Slc2a4 protein, mouse
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Triglycerides
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Cholesterol
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Coenzyme A Ligases
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FAA2 protein, S cerevisiae
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long-chain-fatty-acid-CoA ligase
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Cholic Acid