Cholate inhibits high-fat diet-induced hyperglycemia and obesity with acyl-CoA synthetase mRNA decrease.
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.
Ikemoto
S
S
Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo, Japan.
Takahashi
M
M
Tsunoda
N
N
Maruyama
K
K
Itakura
H
H
Kawanaka
K
K
Tabata
I
I
Higuchi
M
M
Tange
T
T
Yamamoto
T T
TT
Ezaki
O
O
D000704:Analysis of Variance; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology*; D003066:Coenzyme A Ligases / Q000096:biosynthesis*; D004041:Dietary Fats / Q000032:analysis; D002149:Energy Intake; D005227:Fatty Acids / Q000032:analysis / Q000737:chemistry; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051275:Glucose Transporter Type 4; D006943:Hyperglycemia / Q000209:etiology / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D010743:Phospholipids / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis*; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic / Q000187:drug effects*; D014280:Triglycerides / Q000378:metabolism; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D002793:Cholic Acids; D004041:Dietary Fats; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010743:Phospholipids; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C495693:Slc2a4 protein, mouse; D014280:Triglycerides; D002784:Cholesterol; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D019826:Cholic Acid