Vertical sleeve
gastrectomy (VSG) is currently one of the most effective treatments for
obesity. Despite recent developments, the underlying mechanisms that contribute to the metabolic improvements following
bariatric surgery remain unresolved. VSG reduces postprandial intestinal
triglyceride (TG) production, but whether the effects of VSG on intestinal metabolism are related to metabolic outcomes has yet to be established. The
lipid synthesis
enzyme acyl CoA:
monoacylglycerol acyltransferase-2 (Mogat2; MGAT2) plays a crucial role in the assimilation of
dietary fat in the intestine and in regulation of adiposity stores as well. Given the phenotypic similarities between VSG-operated and MGAT2-deficient animals, we reasoned that this
enzyme could also have a key role in mediating the metabolic benefits of VSG. However, VSG reduced
body weight and fat mass and improved
glucose metabolism similarly in whole body MGAT2-deficient (Mogat2(-/-)) mice and wild-type littermates. Furthermore, along with an increase in energy expenditure, surgically naive Mogat2(-/-) mice had altered macronutrient preference, shifting preference away from fat and toward
carbohydrates, and increased locomotor activity. Collectively, these data suggest that the beneficial effects of VSG on
body weight and
glucose metabolism are independent of MGAT2 activity and rather that they are separate from the effects of MGAT2 deficiency. Because MGAT2 inhibitors are proposed as a pharmacotherapeutic option for
obesity, our data suggest that, in addition to increasing energy expenditure, shifting macronutrient preference away from fat could be another important mechanism by which these compounds could contribute to
weight loss.