PMID- 22067315 OWN - NLM STAT- MEDLINE DCOM- 20120305 LR - 20211021 IS - 1945-7170 (Electronic) IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 153 IP - 1 DP - 2012 Jan TI - Type 2 corticotropin-releasing factor receptor in the ventromedial nucleus of hypothalamus is critical in regulating feeding and lipid metabolism in white adipose tissue. PG - 166-76 LID - 10.1210/en.2011-1312 [doi] AB - Ventromedial nucleus of hypothalamus (VMH) plays a critical role in regulating feeding and energy metabolism. The nucleus expresses high levels of the type 2 corticotropin-releasing factor receptor (CRFR2) and receives prominent innervation of nerve fibers containing Urocortin 3 (Ucn 3), an endogenous ligand of the receptor. In the present study, we showed that mice deficient in Ucn 3 had elevated basal feeding and increased nocturnal food intake after overnight fasting compared with the wild-type (WT) littermates. The Ucn 3 null mice also had lower circulating insulin levels compared with those of the WT mice. Interestingly, the mutant mice maintained a comparable body weight with the WT littermates. Mice with reduced CRFR2 expression in the VMH by small hairpin RNA knockdown (KD) recapitulated feeding phenotypes observed in the Ucn 3 null mice. However, VMH CRFR2 KD mice gained significantly more weight than control mice. The weight gain was due to an accumulation of white adipose tissue (WAT) accompanied by reduced plasma free fatty acids and glycerol levels, increased respiratory quotients, and improved glucose tolerance. On the other hand, plasma insulin levels were comparable with the receptor KD and control mice. Furthermore, the expression of several genes, including hormone-sensitive lipase, was significantly reduced in the WAT of VMH CRFR2 KD mice compared with controls. These results indicate that Ucn 3 signaling through CRFR2 is a critical molecular mediator in the VMH in regulating feeding and lipid metabolism in WAT. FAU - Chao, Hongxia AU - Chao H AD - Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22903, USA. FAU - Digruccio, Michael AU - Digruccio M FAU - Chen, Peilin AU - Chen P FAU - Li, Chien AU - Li C LA - eng GR - R01 DK078049/DK/NIDDK NIH HHS/United States GR - R01 DK-078049/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20111108 PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Blood Glucose) RN - 0 (CRF receptor type 2) RN - 0 (Insulin) RN - 0 (Receptors, Corticotropin-Releasing Hormone) RN - 0 (Urocortins) SB - IM MH - Adipose Tissue, White/*metabolism MH - Animals MH - Blood Glucose/metabolism MH - Body Weight MH - Eating/*physiology MH - Energy Metabolism MH - Fasting MH - Gene Knockdown Techniques MH - Glucose Tolerance Test MH - Insulin/blood MH - Insulin Resistance MH - *Lipid Metabolism MH - Male MH - Mice MH - Mice, 129 Strain MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors/genetics/*physiology MH - Urocortins/deficiency/genetics MH - Ventromedial Hypothalamic Nucleus/*physiology PMC - PMC3249673 EDAT- 2011/11/10 06:00 MHDA- 2012/03/06 06:00 PMCR- 2013/01/01 CRDT- 2011/11/10 06:00 PHST- 2011/11/10 06:00 [entrez] PHST- 2011/11/10 06:00 [pubmed] PHST- 2012/03/06 06:00 [medline] PHST- 2013/01/01 00:00 [pmc-release] AID - en.2011-1312 [pii] AID - EN-11-1312 [pii] AID - 10.1210/en.2011-1312 [doi] PST - ppublish SO - Endocrinology. 2012 Jan;153(1):166-76. doi: 10.1210/en.2011-1312. Epub 2011 Nov 8.