Intestine-specific expression of acyl CoA:diacylglycerol acyltransferase 1 reverses resistance to diet-induced hepatic steatosis and obesity in Dgat1-/- mice.

Abstract

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.

• Authors: Bonggi Lee, Angela M Fast, Jiabin Zhu, Ji-Xin Cheng, Kimberly K Buhman
• Journal: Journal of lipid research (J Lipid Res) Vol. 51 Issue 7 Pg. 1770-80 (Jul 2010) ISSN: 1539-7262 [Electronic] United States
• PMID: 20147738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Detergents
• Dietary Fats
• Triglycerides
• Polyethylene Glycols
• Dgat1 protein, mouse
• Diacylglycerol O-Acyltransferase
• tyloxapol

Topics

• Animals
• Detergents (pharmacology)
• Diacylglycerol O-Acyltransferase (genetics, metabolism)
• Diet
• Dietary Fats (metabolism)
• Enterocytes (drug effects, metabolism)
• Fatty Liver (metabolism)
• Female
• Intestines (cytology, enzymology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Obesity (metabolism)
• Polyethylene Glycols (pharmacology)
• Transgenes
• Triglycerides (blood)