Loss of melanocortin receptor accessory protein 2 in melanocortin-4 receptor neurons protect from obesity-associated autonomic and cardiovascular dysfunctions.

ABSTRACT:

Aims

The melanocortin receptor accessory protein 2 (MRAP2), which is abundantly expressed in the brain including the hypothalamus, has emerged as a key regulator of melanocortin-4 receptor (MC4R) activity. We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on metabolic, autonomic and cardiovascular functions.

Methods and results

Selective deletion of MRAP2 in MC4R neurons causes obesity that was associated with hyperphagia and impairment in glucose homeostasis and insulin sensitivity. MC4R agonist Melatonan II (MTII)-induced anorectic effects were blunted in mice lacking MRAP2 in MC4R neurons, whereas Celastrol retained its efficacy in reducing food intake and body weight. MRAP2 deletion also reduced baseline sympathetic n

SUBMITTER: Guo DF 

PROVIDER: S-EPMC12551390 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature