Prolyl Carboxypeptidase Regulates Energy Expenditure and the Thyroid Axis.

Source

Program in Integrative Cell Signaling and Neurobiology of Metabolism (J.K.J., G.S., K.K., S.D.) and Departments of Obstetrics and Gynecology and Reproductive Sciences (J.K.J., G.S., K.K., S.D.), Neurobiology (S.D.), and Comparative Medicine (S.D.), Yale University School of Medicine, New Haven, Connecticut 06520-208063.

Abstract

Hypothalamic ?-melanocyte-stimulating hormone (?-MSH) plays a central role in regulating energy uptake and expenditure. Prolyl carboxypeptidase (PRCP), a protease expressed in the hypothalamus, is responsible for the degradation of ?-MSH. PRCP null animals (PRCP(gt/gt) mice) display elevated ?-MSH in the hypothalamus, lower body weight, and are protected from diet induced obesity. Here, we report that PRCP(gt/gt) mice have a significant decrease in fat mass, although an increase in lean mass was also observed. In agreement with low fat accumulation, reduced leptin levels were found. Consistent with the effect of ?-MSH on energy metabolism, PRCP(gt/gt) mice had increased energy expenditure with elevated circulating thyroid hormone levels and brown adipose tissue uncoupling protein 1 mRNA levels compared with control mice when exposed to regular diet. TRH mRNA levels in the PVN were significantly higher in fed PRCP(gt/gt) animals compared with fed wild-type controls. Fasting significantly decreased TRH mRNA levels in both PRCP(gt/gt) and wild-type (WT) mice. However, TRH mRNA levels in fasted PRCP(gt/gt) animals were significantly higher than those of fasted WT mice. Refeeding analysis after fasting showed a reduced food intake in PRCP(gt/gt) compared with WT mice. Finally, TRH mRNA levels in T(3)-treated hypothyroid PRCP(gt/gt) mice showed a non significant reduction compared with those of hypothyroid PRCP(gt/gt) mice, supporting the impairment of the hypothalamo-pituitary-thyroid axis in PRCP(gt/gt) mice. All together, these data confirm that PRCP plays a role in the regulation of energy metabolism.

Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=22202165&dopt=Abstract

cbs news manny pacquiao fight pacquiao marquez pacquiao marquez penn state game radiohead tour cbsnews