Over‐expression of monoacylglycerol lipase (MGL) in mouse small intestine results in an obese phenotype

Abstract

We recently demonstrated that, in addition to the well known anabolic metabolism of intestinal MG, MG hydrolytic activity and expression of the MG lipase (MGL) gene were present in rodent small intestine. The function of small intestinal MGL is unknown. We therefore generated transgenic mice (iMGL mice) that over‐expressed MGL specifically in small intestine using the intestinal fatty acid binding protein promoter. Marked induction of transgenic MGL mRNA was found in transgenic animals and intestinal specific expression of the transgene was confirmed. Western analysis and MGL activity measurements were also performed. Following 3 weeks of high fat feeding (40% Kcal), body weight gain and total fat pad weight were significantly increased in iMGL mice compared to non‐transgenic littermates. DXA measurements showed that body fat mass was significantly higher in the iMGL mice whereas lean mass was not altered. Triacylglycerol (TG) content of intestinal mucosa and liver were also increased in iMGL mice. Plasma TG levels in iMGL mice were high but free fatty acid and total cholesterol levels were not changed. The metabolism of 14C oleate and 3H monoolein in small intestinal mucosa were not substantially altered, although less labeled MG remained following in vivo incubation, likely due to the action of the MGL transgene. Food intake data showed that the iMGL mice were hyperphagic. Based on this phenotype, we hypothesize a role for intestinal MGL in whole body energy balance, possibly via regulation of food intake.