Hypoxic stimulus alters hypothalamic AMP-activated protein kinase phosphorylation concomitant to hypophagia.
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.
Simler
N
N
CRSSA, Department of Human Factors, BP 87, 38702 La Tronche Cedex, France.
Malgoyre
A
A
Koulmann
N
N
Alonso
A
A
Peinnequin
A
A
Bigard
A X
AX
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
D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases