Prolyl Carboxypeptidase Regulates Energy Expenditure and the Thyroid Axis
- 1 February 2012
- journal article
- other
- Published by The Endocrine Society in Endocrinology
- Vol. 153 (2), 683-689
- https://doi.org/10.1210/en.2011-1399
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 (PRCPgt/gt mice) display elevated α-MSH in the hypothalamus, lower body weight, and are protected from diet induced obesity. Here, we report that PRCPgt/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, PRCPgt/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 PRCPgt/gt animals compared with fed wild-type controls. Fasting significantly decreased TRH mRNA levels in both PRCPgt/gt and wild-type (WT) mice. However, TRH mRNA levels in fasted PRCPgt/gt animals were significantly higher than those of fasted WT mice. Refeeding analysis after fasting showed a reduced food intake in PRCPgt/gt compared with WT mice. Finally, TRH mRNA levels in T3-treated hypothyroid PRCPgt/gt mice showed a non significant reduction compared with those of hypothyroid PRCPgt/gt mice, supporting the impairment of the hypothalamo-pituitary-thyroid axis in PRCPgt/gt mice. All together, these data confirm that PRCP plays a role in the regulation of energy metabolism.Keywords
This publication has 24 references indexed in Scilit:
- Distribution of hypophysiotropic thyrotropin‐releasing hormone (TRH)‐synthesizing neurons in the hypothalamic paraventricular nucleus of the mouseJournal of Comparative Neurology, 2010
- Hypophysiotropic Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Human Hypothalamus Are Innervated by Neuropeptide Y, Agouti-Related Protein, and α-Melanocyte-Stimulating Hormone1Journal of Clinical Endocrinology & Metabolism, 2000
- Central nervous system control of food intakeNature, 2000
- Leptin-induced increase in sympathetic nervous and cardiovascular tone is mediated by proopiomelanocortin (POMC) productsBrain Research Bulletin, 1999
- Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obeseNature, 1997
- Characterization of melanocortin receptor subtype expression in murine adipose tissues and in the 3T3-L1 cell line.Endocrinology, 1996
- Thyroid Hormone Control of Thermogenesis and Energy BalanceThyroid®, 1995
- Immunocytochemical Delineation of Thyrotrophic Area: Origin of Thyrotropin-Releasing Hormone in the Median EminenceNeuroendocrinology, 1988
- Separate neurons in the paraventricular nucleus project to the median eminence and to the medulla or spinal cordBrain Research, 1980
- Paraventricular Nucleus:A Site for the Integration of Neuroendocrine and Autonomic MechanismsNeuroendocrinology, 1980