PMID- 22202165
OWN - NLM
STAT- MEDLINE
DCOM- 20120327
LR  - 20211021
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 153
IP  - 2
DP  - 2012 Feb
TI  - Prolyl carboxypeptidase regulates energy expenditure and the thyroid axis.
PG  - 683-9
LID - 10.1210/en.2011-1399 [doi]
AB  - Hypothalamic alpha-melanocyte-stimulating hormone (alpha-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 
      alpha-MSH. PRCP null animals (PRCP(gt/gt) mice) display elevated alpha-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 
      alpha-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.
FAU - Jeong, Jin Kwon
AU  - Jeong JK
AD  - Department of Obstetrics and Gynecology and Reproductive Sciences, Yale 
      University School of Medicine, P.O. Box 208063, New Haven, Connecticut 
      06520-208063, USA.
FAU - Szabo, Gyorgyi
AU  - Szabo G
FAU - Kelly, Kaitlin
AU  - Kelly K
FAU - Diano, Sabrina
AU  - Diano S
LA  - eng
GR  - R01 DK084065/DK/NIDDK NIH HHS/United States
GR  - DK 084065/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111227
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Ion Channels)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ucp1 protein, mouse)
RN  - 0 (Uncoupling Protein 1)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 9002-71-5 (Thyrotropin)
RN  - EC 3.4.- (Carboxypeptidases)
RN  - EC 3.4.16.2 (lysosomal Pro-X carboxypeptidase)
SB  - IM
MH  - Adipose Tissue, Brown/metabolism
MH  - Animals
MH  - Carboxypeptidases/genetics/*metabolism
MH  - Energy Metabolism/*physiology
MH  - Gene Expression Regulation/physiology
MH  - Hypothalamus/enzymology
MH  - Hypothyroidism/metabolism
MH  - Ion Channels/genetics/metabolism
MH  - Mice
MH  - Mitochondrial Proteins/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Thyroid Gland/*metabolism
MH  - Thyrotropin/genetics/metabolism
MH  - Triiodothyronine/metabolism
MH  - Uncoupling Protein 1
PMC - PMC3275392
EDAT- 2011/12/29 06:00
MHDA- 2012/03/28 06:00
PMCR- 2013/02/01
CRDT- 2011/12/29 06:00
PHST- 2011/12/29 06:00 [entrez]
PHST- 2011/12/29 06:00 [pubmed]
PHST- 2012/03/28 06:00 [medline]
PHST- 2013/02/01 00:00 [pmc-release]
AID - en.2011-1399 [pii]
AID - EN-11-1399 [pii]
AID - 10.1210/en.2011-1399 [doi]
PST - ppublish
SO  - Endocrinology. 2012 Feb;153(2):683-9. doi: 10.1210/en.2011-1399. Epub 2011 Dec 
      27.