Introduction: The hypothalamic hormone orexin-A (OXA) increases food and water intake, regulates the sleep-wake cycle, muscle tone and energy balance. AMP-activated protein kinase (AMPK) is an important metabolic regulator with direct hypothalamic orexigenic and diverse peripheral effects including fat tissue and muscle.
Aims: We aimed to study the influence of OXA on the activity of AMPK in the hypothalamus, subcutaneous and visceral adipose tissues, and skeletal muscle.
Methods: Thirty minutes after intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of OXA to male Wistar rats, tissues were rapidly dissected and protein extracts were immunoprecipitated and the AMPK activity was determined by an in vitro kinase assay.
Results: AMPK activity significantly increased in the hypothalamus the after i.c.v. OXA administration (172±15.8 pmol ATP/min per mg protein (control, mean±S.E.M.), 236±11.5 (OXA) P=0.0022, n=68). The AMPK activity decreased in white adipose tissues after i.p. OXA administration (subcutaneous fat: 52±14.3 (control), 14±2.9 (OXA), P=0.0121; visceral fat: 76±6.8 (control), 41±6.3 (OXA), P=0.0173). In the skeletal muscle neither types of OXA administration had effect on AMPK activity.
Conclusion: Central administration of OXA increases appetite by the elevation of the AMPK activity in the hypothalamus. Peripheral administration of OXA reduces the AMPK activity in both subcutaneous and visceral white adipose tissues, which could lead to increased fat stores.
30 Apr - 04 May 2011
European Society of Endocrinology