Enhancing energy and glucose metabolism by disrupting triglyceride synthesis: Lessons from mice lacking DGAT1 - PubMed (original) (raw)

Enhancing energy and glucose metabolism by disrupting triglyceride synthesis: Lessons from mice lacking DGAT1

Hubert C Chen. Nutr Metab (Lond). 2006.

Abstract

Although the ability to make triglycerides is essential for normal physiology, excess accumulation of triglycerides results in obesity and is associated with insulin resistance. Inhibition of triglyceride synthesis, therefore, may represent a feasible strategy for the treatment of obesity and type 2 diabetes. Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 have increased energy expenditure and insulin sensitivity and are protected against diet-induced obesity and glucose intolerance. These metabolic effects of DGAT1 deficiency result in part from the altered secretion of adipocyte-derived factors. Studies of DGAT1-deficient mice have helped to provide insights into the mechanisms by which cellular lipid metabolism modulates systemic carbohydrate and insulin metabolism, and a better understanding of how DGAT1 deficiency enhances energy expenditure and insulin sensitivity may identify additional targets or strategies for the treatment of obesity and type 2 diabetes.

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Figures

Figure 1

Figure 1

Increased insulin sensitivity in _Dgat1_-/- mice. A. Glucose tolerance test. B. Insulin tolerance test. C. Hyperinsulinemic-euglycemic clamp study. Reproduced with permission from [3].

Figure 2

Figure 2

Obesity resistance and enhanced glucose tolerance in WT mice transplanted with _Dgat1_-/- WAT. A. Body weight response to high-fat feeding. Mice were placed on a high-fat diet one week after fat transplantation. B. Glucose tolerance test. Reproduced with permission from [9].

References

    1. Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese RV., Jr Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking DGAT. Nat Genet. 2000;25:87–90. doi: 10.1038/75651. -DOI -PubMed
    1. Chen HC, Farese RV., Jr DGAT and triglyceride synthesis: A new target for obesity treatment? Trends Cardiovasc Me. 2000;10:188–192. doi: 10.1016/S1050-1738(00)00066-9. -DOI -PubMed
    1. Yen CL, Monetti M, Burri BJ, Farese RV., Jr The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters. J Lipid Res. 2005;46:1502–1511. doi: 10.1194/jlr.M500036-JLR200. -DOI -PubMed
    1. Chen HC, Smith SJ, Ladha Z, Jensen DR, Ferreira LD, Pulawa LK, McGuire JG, Pitas RE, Eckel RH, Farese RV., Jr Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1. J Clin Invest. 2002;109:1049–1055. doi: 10.1172/JCI200214672. -DOI -PMC -PubMed
    1. Cao J, Burn P, Shi Y. Properties of the mouse intestinal acyl-CoA:monoacylglycerol acyltransferase, MGAT2. J Biol Chem. 2003;278:25657–25663. doi: 10.1074/jbc.M302835200. -DOI -PubMed

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