Triacylglycerol synthesis, energy metabolism, and glucose homeostasis: A gut reaction?

Abstract

The intestine plays a pivotal role in regulating systemic metabolism. It is the portal and sensor for incoming nutrients and the origin of neural and endocrine signals that determine responses to diet. Importantly, the intestine is the location where host, diet, and gut microbiota interact. We have discovered that acyl CoA:monoacylglycerol acyltransferase 2 (MGAT2) catalyzes triacylglycerol synthesis in enterocytes, mediates fat absorption in the intestine, and regulates whole body energy balance. Mice without a functional gene encoding the enzyme (Mogat2−/−) absorb a normal amount of dietary fat. However, they exhibit delayed fat absorption, altered gut hormone secretion, and increased energy expenditure. As a result, they are resistant to obesity and related metabolic disorders induced by a high‐fat diet. Using tissue‐specific gain‐ and loss‐of‐function models, we showed that intestinal MGAT2 enhances metabolic efficiency and promotes weight gain. When fed a fat‐free diet, Mogat2−/− mice still exhibit increased energy expenditure, suggesting the effects are not limited to calories from fat. Accordingly, MGAT2 deficiency protects the genetically hyperphagic Agouti mouse fed a regular chow from excessive weight gain, hepatic steatosis, and glucose intolerance. We also found that inactivation of MGAT2 in adult mice decreases weight gain and enhances glucose regulation, even in already obese mice. Surprisingly, Mogat2−/− mice are also protected from both chemical and genetic insults to the pancreatic beta‐cells. We hypothesize that loss of MGAT2 may act on beta‐cells through its effect on bile acid‐modifying gut microbiota. Some of these findings and approaches we are taking to test this hypothesis will be discussed in this presentation.Support or Funding InformationWe gratefully acknowledge our funding support from the U.S. National Institutes of Health (DK088210) and U.S. Department of Agriculture (WIS01442).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.