Intestine-specific expression of acyl CoA:diacylglycerol acyltransferase 1 reverses resistance to diet-induced hepatic steatosis and obesity in Dgat1-/- mice.
Mice deficient in acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in triacylglycerol (TG) biosynthesis, are resistant to high-fat (HF) diet-induced hepatic steatosis and obesity. DGAT1-deficient (Dgat1-/-) mice have no defect in quantitative absorption of dietary fat; however, they have abnormally high levels of TG stored in the cytoplasm of enterocytes, and they have a reduced postprandial triglyceridemic response. We generated mice expressing DGAT1 only in the intestine (Dgat1IntONLY) to determine whether this phenotype contributes to resistance to HF diet-induced hepatic steatosis and obesity in Dgat1-/- mice. Despite lacking DGAT1 in liver and adipose tissue, we found that Dgat1IntONLY mice are not resistant to HF diet-induced hepatic steatosis or obesity. The results presented demonstrate that intestinal DGAT1 stimulates dietary fat secretion out of enterocytes and that altering this cellular function alters the fate of dietary fat in specific tissues.
Department of Foods and Nutrition, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Bonggi
B
Lee
Angela M
AM
Fast
Jiabin
J
Zhu
Ji-Xin
JX
Cheng
Kimberly K
KK
Buhman
D000818:Animals; D003902:Detergents / Q000494:pharmacology; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D007422:Intestines / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology; D019076:Transgenes; D014280:Triglycerides / Q000097:blood
D003902:Detergents; D004041:Dietary Fats; D014280:Triglycerides; D011092:Polyethylene Glycols; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; C016811:tyloxapol