Acyl-CoA:Diacylglycerol Acyltransferase: A Key Player in the Regulation of Fatty Acid and Glucose Metabolism in Mammalian Systems

Abstract

Acyl-CoA:diacylglycerol acyltransferase (DGAT) is a critical enzyme involved in the last committed step of triglyceride synthesis. DGAT has two known isoforms that are expressed in various tissues being crucial to energy homeostasis in mammals. DGAT inhibits the accumulation of diacylglycerol, a lipid thought to promote insulin resistance, by incorporating them into triglyceride. However, both deletion and overexpression studies targeting DGAT have resulted in decreased diacylglycerol content and caused increased insulin sensitivity. Studies analyzing obese models though have noticed a positive correlation between DGAT and obesity. Thus, it remains elucidated whether DGAT plays a causal role in the development of diet-related diseases or provides protection by preventing accumulation of diacylglycerol. The purpose of this review is to present an overview of DGAT, state factors that may influence its expression, explain the potential consequences of DGAT overexpression or deficiency, and discuss its relative importance to glucose metabolism and energy storage.