Intestine, assimilation of dietary fat, triacylglycerol synthesis, and energy balance
Our research focuses on the physiological functions of triacylglycerol (triglyceride; TG) synthesis. TG serves as a storage and transport molecule of bioactive fatty acids and its synthesis is essential for many biological processes, including the absorption of dietary fat and the production of milk. Excessive accumulation of TG, however, leads to obesity and related metabolic diseases, such as type 2 diabetes. Using genetically engineered mice, we examine the physiological functions of enzymes involved in the synthesis of TG. One current focus is on the acyl CoA:monoacylglycerol acyltransferase MGAT2, which mediates fat absorption in the small intestine. Mice lacking the enzyme are protected against obesity and other metabolic disorders normally induced by high-fat feeding. Interestingly, they absorb a normal quantity of dietary fat but exhibit increases in energy expenditure. We are now combining biochemical and systems biology approaches to understand the molecular mechanisms by which intestinal lipid metabolism regulates systemic energy balance. This is a research area of critical importance. Several MGAT2 inhibitors have been developed and are being tested for efficacy. Our on-going research has also expanded into other functions of MGATs and additional genetic and dietary factors modulating energy balance. The ultimate goals of these studies are to better understand the fundamental process of fat assimilation and to explore new approaches to prevent or treat obesity and other metabolic diseases associated with excessive fat intake and energy storage.
Banh T, Nelson DW, Gao Y, Huang TN, Yen MI, Yen C–LE. (2015). Adult-onset deficiency of acyl CoA:monoacylglycerol acyltransferase (MGAT) 2 protects mice from diet-induced obesity and glucose intolerance. J. Lipid Res. DOI: 10.1194/jlr.M055228 Epub 2014 Dec 22
Yen C–LE*, Nelson DW, Yen MI. (2015). Intestinal Triacylglycerol Synthesis in Fat Absorption and Systemic Energy Metabolism. J. Lipid Res. DOI:10.1194/jlr.Ro52902 Epub 2014 Sep 17
Nelson DW, Gao Y, Yen MI, and Yen C–LE*. (2014). Intestine–specific deletion of acyl CoA: monoacyltransferase (MGAT) 2 protects mice from diet–induced obesity and glucose intolerance. J. Biol. Chem. DOI: 10.1074/jbc.M114.555961. Epub 2014 May 1.
Gao Y, Nelson DW, Banh T, Yen MI and Yen C-LE. (2013). Intestine-specific expression of MOGAT2 partially restores metabolic efficiency in Mogat2-deficient mice. J. Lipid Res. 54(6):1644-52.
Nelson DW, Gao Y, Spencer NM, Bahn T, and Yen C-LE. (2011). Deficiency of the monoacylglycerol acyltransferase MGAT2 increases energy expenditure without high-fat feeding and protects genetically obese mice from excessive weight gain. J. Lipid Res. 52(9):1723-32.
Yen C-LE, Cheong M-L, Grueter C, Zhou P, Moriwaki J, Wong JS, Hubbard B, Marmor S, and Farese RV Jr. (2009). Deficiency of the intestinal enzyme MGAT2 protects mice from metabolic disorders induced by high-fat feeding. Nature Medicine. Published online: 15 March 2009 | doi:10.1038/nm.1937
Yen C-LE, Stone SJ, Koliwad S, Harris C, and Farese RV Jr. (2008). DGAT enzymes and triacylglycerol biosynthesis. J. Lipid Res. 49(11):2283-301. Epub 2008 Aug 29. Review.
Yen C-LE*, Monetti M, Burri BJ, and Farese RV Jr. (2005). The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, wax esters, and retinyl esters. J. Lipid Res. 46(7):1502-11
Yen C-LE and Farese RV Jr. (2003). MGAT2, a monoacylglycerol acyltransferase expressed in the small intestine. J. Biol. Chem. 278(20):18532-7
Yen C-LE, Stone SJ, Cases S, Zhou P, Farese RV Jr. (2002). Identification of a gene encoding MGAT1, a monoacylglycerol acyltransferase. Proc. Natl. Acad. Sci. USA. 99(13):8512–8517.