Endocrine Abstracts (2011) 26 P341

Effects of Orexin-A on AMPK activity

A H Molnár1,2, G K Kis2, C Varga2, K Rákosi3, M Scerif4, F A László2, F László1,2 & M Korbonits4


1Institute of Physical Education and Sport Sciences, University of Szeged, Szeged, Hungary; 2Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary; 3Department of Medical Chemistry, University of Szeged, Szeged, Hungary; 4Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, UK.


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=6–8). 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.

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