title: Hypoxic stimulus alters hypothalamic AMP-activated protein kinase phosphorylation concomitant to hypophagia.
abstract: Acute exposure to hypobaric hypoxia is known to decrease food intake, but the molecular mechanisms of such alteration in feeding behavior remain unknown. We tested the hypothesis that hypothalamic AMP-activated protein kinase (AMPK) phosphorylation is affected by acute exposure to hypobaric hypoxia and thus would be involved in initial anorexia. To address this issue, male rats weighing 255-270 g were either submitted to hypobaric hypoxia (H, equivalent altitude of 5,500 m), maintained under local barometric pressure conditions (N), or pair-fed an equivalent quantity of food to that consumed by H rats (PF), for 6, 24, or 48 h. Daily food intake dropped by 73% during the first day of hypoxia (P<0.01) and remained by 46% lower than in N rats thereafter (P<0.01). Hypoxia per se, as estimated by comparing experimental data between the H and PF groups, increased ob gene transcription and plasma leptin concentration. A transient increase in glucose availability occurred in the H group compared with PF animals (P<0.05). The hypoxic stimulus led to an early and transient decrease in hypothalamic AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, concomitant with hypophagia and associated alterations in nutrients and hormones. An increase in NPY mRNA levels occurred from day 1, similarly in H and PF rats, and thus mainly related to food restriction alone (P<0.05). In conclusion, the present study demonstrates that hypoxia per se inhibited AMPK and ACC phosphorylation in the hypothalamus, concomitant with profound anorexia. A powerful counterregulation occurs rapidly, mediated by NPY and devoted to avoid prolonged anorexia.
authors.affiliation: CRSSA, Department of Human Factors, BP 87, 38702 La Tronche Cedex, France.
authors.forename: N
authors.initials: N
authors.lastname: Simler
authors.forename: A
authors.initials: A
authors.lastname: Malgoyre
authors.forename: N
authors.initials: N
authors.lastname: Koulmann
authors.forename: A
authors.initials: A
authors.lastname: Alonso
authors.forename: A
authors.initials: A
authors.lastname: Peinnequin
authors.forename: A X
authors.initials: AX
authors.lastname: Bigard
mesh_terms: D055372:AMP-Activated Protein Kinases; D000222:Adaptation, Physiological; D000818:Animals; D005247:Feeding Behavior; D001068:Feeding and Eating Disorders / Q000503:physiopathology*; D007031:Hypothalamus / Q000201:enzymology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases