Anti-AGRP polyclonal antibody [Biotin]

The hypothalamic melanocortin system composed of proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons plays a key role in maintaining energy homeostasis. The POMC-derived peptides, alpha-MSH and beta-EP, have distinct roles in this process. alpha-MSH inhibits food intake, whereas beta-EP, an endogenous opioid, can inhibit POMC neurons and stimulate food intake. A mouse model was used to examine the effects of opioid antagonism with naltrexone (NTX) on Pomc and Agrp gene expression and POMC peptide processing in the hypothalamus in conjunction with changes in energy balance. There were clear stimulatory effects of NTX on hypothalamic Pomc in mice receiving low-and high-fat diets, yet only transient decreases in food intake and body weight gain were noted. The effects on Pomc expression were accompanied by an increase in POMC prohormone levels and a decrease in levels of the processed peptides alpha-MSH and beta-EP. Arcuate expression of the POMC processing enzymes Pcsk1, Pcsk2, and Cpe was not altered by NTX, but expression of Prcp, an enzyme that inactivates alpha-MSH, increased after NTX exposure. NTX exposure also stimulated hypothalamic Agrp expression, but the effects of NTX on energy balance were not enhanced in Agrp-null mice. Despite clear stimulatory effects of NTX on Pomc expression in the hypothalamus, only modest transient decreases in food intake and body weight were seen. Effects of NTX on POMC processing, and possibly alpha-MSH inactivation, as well as stimulatory effects on AgRP neurons could mitigate the effects of NTX on energy balance. Copyright (C) 2019 Endocrine Society

Adiponectin regulates glucose and lipid metabolism, acting against atherosclerosis and metabolic syndrome. Accumulating evidences suggest that adiponectin acts on the brain including the arcuate nucleus of hypothalamus (ARC). The ARC contains orexigenic neuropeptide Y (NPY)/agouti related peptide (AgRP) neurons and anorexigenic proopiomelanocortin (POMC) neurons, the first order neurons for feeding regulation. We recently reported that intracerebroventricular injection of adiponectin at low glucose level suppressed food intake, while at elevated glucose level it promoted food intake, exhibiting glucose-dependent reciprocal effects. As an underlying neuronal mechanism, physiological level of adiponectin at low glucose activated ARC POMC neurons and at high glucose inactivated them. Now, whether physiological level of adiponectin also affects NPY/AgRP neurons is essential for fully understanding the adiponectin action, but it remains to be clarified. We here report that a physiological dose of adiponectin, in both high and low glucose conditions, attenuated action potential firing without altering resting membrane potential in ARC NPY neurons. This adiponectin effect was abolished by GABAA receptor blockade. Adiponectin enhanced amplitude but not frequency of inhibitory postsynaptic current (IPSC) onto NPY neurons. These results demonstrate that adiponectin enhances IPSC onto NPY neurons to attenuate action potential firing in NPY neurons in a glucose-independent manner, being contrasted to its glucose-dependent effect on POMC neurons.