Canna~Fangled Abstracts

The role of AMP-activated protein kinase (AMPK) in the androgenic potentiation of cannabinoid-induced changes in energy homeostasis.

By December 30, 2014 No Comments
2014 Dec 30:ajpendo.00421.2014. doi: 10.1152/ajpendo.00421.2014. [Epub ahead of print]

pm1The role of AMP-activated protein kinase (AMPK) in the androgenic potentiation of cannabinoid-induced changes in energy homeostasis.

Abstract

Orexigenic mediators can impact the hypothalamic feeding circuitry via the activation of AMP-dependent protein kinase (AMPK). Given that testosterone is an orexigenic hormone, we hypothesized that androgenic changes in energy balance are due to enhanced cannabinoid-induced inhibition of anorexigenic proopiomelanocortin (POMC) neurons via activation of AMPK. To this end, whole animal experiments were carried out in gonadectomized male guinea pigs treated subcutaneously with either testosterone propionate (TP; 400μg) or its sesame oil vehicle (0.1mL). TP-treated animals displayed increases in energy intake associated with increases in meal size. TP also increased several indices of energy expenditure, as well as the pAMPK/AMPK ratio in the arcuate nucleus (ARC) measured 2 and 24 hours post-treatment. Subcutaneous administration of the CB1 receptor antagonist AM251 (3mg/kg) rapidly blocked the hyperphagic effect of TP. This was largely mimicked upon third ventricular administration of AM251 (10μg). Electrophysiologic studies revealed that TP potentiated the ability of the cannabinoid receptor agonist WIN 55,212-2 to decrease the frequency of miniature excitatory postsynaptic currents in ARC neurons. TP also increased the basal frequency of miniature inhibitory postsynaptic currents. In addition, depolarization-induced suppression (DSE) is potentiated in cells from TP-treated animals, and blocked by AM251. The AMPK inhibitor Compound C attenuated DSE from TP-treated animals, whereas AMPK activator metformin enhanced DSE from vehicle-treated animals. These effects occurred in a sizable number of identified POMC neurons. Collectively, these results indicate that the androgen-induced increases in energy intake are mediated via an AMPK-dependent augmentation in endocannabinoid tone onto POMC neurons.
Copyright © 2014, American Journal of Physiology – Endocrinology and Metabolism.

KEYWORDS:

AMPK; POMC; cannabinoid; energy balance; testosterone

PMID:

 25550281
[PubMed – as supplied by publisher]

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