Another Obesity-modulating Gene Revealed
JAX® NOTES Issue 514, Summer 2009
Is it possible to stay lean but eat a high fat diet? Yes, if you're a C57BL/6J mouse (000664, B6) deficient for a gene called acylCoA; monoacylglycerol acyltransferase-2 (Mogat2). So reports a research team from the Gladstone Institute of Cardiovascular Disease, San Francisco, California (Yen et al. 2009). The Mogat2-deficient B6 mice engineered by the team appear normal in every way, except that they lack the MGAT2 protein and have 50% less intestinal MGAT activity than normal B6 mice. When fed a low-fat chow diet, they gain weight normally and have a normal body composition. However, when fed a high-fat diet, they, especially the males, gain significantly less weight and are significantly leaner than comparably fed B6 controls. Additionally, male Mogat2-/- B6 mice fed a high-fat diet have lower fasting insulin concentrations, better glucose tolerance, and lower fasting concentrations of total and non-high-density lipoprotein cholesterol in plasma than normal B6 mice. Finally, Mogat2-/- B6 mice are resistant to hepatic steatosis (accumulating fat in the liver). The authors conclude that MGAT2 deficiency protects B6 mice against high fat diet-induced obesity, and that inhibiting MGAT2's action in humans may someday be used to treat diet-induced metabolic diseases.
 |
|
Compared to Mogat2-deficient B6 mice fed a high fat diet, comparably fed normal B6 mice gain considerably more weight. |
Reference
Yen CL, Cheong ML, Grueter C, Zhou P, Moriwaki J, Wong JS, Hubbard B, Marmor S, Farese RV Jr. 2009. Deficiency of the intestinal enzyme acyl CoA:monoacylglycerol acyltransferase-2 protects mice from metabolic disorders induced by high-fat feeding. Nat Med 15:442-6.
