Mex3c Mutation Reduces Adiposity and Increases Energy Expenditure

The function of MEX3C, the mammalian homolog ofCaenorhabditis elegans RNA-binding protein muscle excess 3 (MEX-3), was unknown until our recent report that MEX3C is necessary for normal postnatal growth and enhances the expression of local boneIgf1 expression. Here we report the pivotal role ofMex3c in energy balance regulation.Mex3c mutation caused leanness in both heterozygous and homozygous transgenic mice, as well as a more beneficial blood glucose and lipid profile in homozygous transgenic mice, in both sexes. Although transgenic mice showed normal food intake and fecal lipid excretion, they had increased energy expenditure independent of physical activity. Mutant mice had normal body temperature,Ucp1 expression in brown adipose tissue, and muscle and liver fatty acid oxidation.Mex3c is expressed in neurons and is detectable in the arcuate nucleus, the ventromedial nucleus, and the dorsomedial nucleus of the hypothalamus.Mex3c was not detected in NPY or POMC neurons but was detected in leptin-responsive neurons in the ventromedial nucleus.Mex3c andLeptin double mutant mice were growth retarded and obese and had blood profiles similar to those ofob/ob mice but showed none of the steatosis observed inob/ob mice. Our data show thatMex3c is involved in energy balance regulation.