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

@entity3033 @entity251 @entity840 @entity14513 @entity10024 @entity342 @entity43313 @entity860 @entity5420 @entity2449
UNASSIGNED: Orexigenic mediators can impact the hypothalamic feeding circuitry via the activation of @entity860 -dependent protein kinase (AMPK). Given that @entity251 is an orexigenic hormone, we hypothesized that androgenic changes in energy balance are due to enhanced cannabinoid-induced inhibition of anorexigenic proopiomelanocortin ( @entity43313 ) neurons via activation of AMPK. To this end, whole animal experiments were carried out in gonadectomized male @entity840 treated subcutaneously with either @entity3033 (TP; 400 g) or its @entity5420 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 @entity14513 (3mg/kg) rapidly blocked the hyperphagic effect of TP. This was largely mimicked upon third ventricular administration of @entity14513 (10 g). Electrophysiologic studies revealed that TP potentiated the ability of the cannabinoid receptor agonist @entity10024 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 @entity14513 . The AMPK inhibitor Compound C attenuated DSE from TP-treated animals, whereas AMPK activator @entity2449 enhanced DSE from vehicle-treated animals. These effects occurred in a sizable number of identified @entity43313 neurons. Collectively, these results indicate that the @entity342 -induced increases in energy intake are mediated via an AMPK-dependent augmentation in endocannabinoid tone onto @entity43313 neurons.
