Format

Send to

Choose Destination
Endocrinology. 2012 Feb;153(2):683-9. doi: 10.1210/en.2011-1399. Epub 2011 Dec 27.

Prolyl carboxypeptidase regulates energy expenditure and the thyroid axis.

Author information

1
Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, P.O. Box 208063, New Haven, Connecticut 06520-208063, USA.

Abstract

Hypothalamic α-melanocyte-stimulating hormone (α-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 α-MSH. PRCP null animals (PRCP(gt/gt) mice) display elevated α-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 α-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.

PMID:
22202165
PMCID:
PMC3275392
DOI:
10.1210/en.2011-1399
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center