title: PGC-1α expression in murine AgRP neurons regulates food intake and energy balance.
abstract: OBJECTIVE
  Food intake and whole-body energy homeostasis are controlled by agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons located in the arcuate nucleus of the hypothalamus. Key energy sensors, such as the AMP-activated protein kinase (AMPK) or sirtuin 1 (SIRT1), are essential in AgRP and POMC cells to ensure proper energy balance. In peripheral tissues, the transcriptional coactivator PGC-1α closely associates with these sensors to regulate cellular metabolism. The role of PGC-1α in the ARC nucleus, however, remains unknown.
  
  
  METHODS
  Using AgRP and POMC neurons specific knockout (KO) mouse models we studied the consequences of PGC-1α deletion on metabolic parameters during fed and fasted states and on ghrelin and leptin responses. We also took advantage of an immortalized AgRP cell line to assess the impact of PGC-1α modulation on fasting induced AgRP expression.
  
  
  RESULTS
  PGC-1α is dispensable for POMC functions in both fed and fasted states. In stark contrast, mice carrying a specific deletion of PGC-1α in AgRP neurons display increased adiposity concomitant with significantly lower body temperature and RER values during nighttime. In addition, the absence of PGC-1α in AgRP neurons reduces food intake in the fed and fasted states and alters the response to leptin. Finally, both in vivo and in an immortalized AgRP cell line, PGC-1α modulates AgRP expression induction upon fasting.
  
  
  CONCLUSIONS
  Collectively, our results highlight a role for PGC-1α in the regulation of AgRP neuronal functions in the control of food intake and peripheral metabolism.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland. Electronic address: jonathan.gill@unibas.ch.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Gill
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland. Electronic address: julien.delezie@unibas.ch.
authors.forename: Julien
authors.initials: J
authors.lastname: Delezie
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland. Electronic address: gesa.santos@unibas.ch.
authors.forename: Gesa
authors.initials: G
authors.lastname: Santos
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland. Electronic address: christoph.handschin@unibas.ch.
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
keywords: AMPK, AMP-activated protein kinase; AgRP, Agouti-related protein; Agouti-related protein; Energy homeostasis; FOXO1, Forkhead protein 1; Metabolism; PGC-1α; PGC-1α, Peroxisome proliferator-activated receptor γ coactivator 1α; POMC, Pro-opiomelanocortin; Pro-opiomelanocortin; SIRT1, NAD+-dependent protein deacetylase sirtuin-1; TBP, TATA-binding protein; Transcriptional regulation