Pro-opiomelanocortin (POMC) is the archetypal polypeptide precursor of hormones and neuropeptides. It plays a crucial role in integrating a range of vital physiological functions, such as maintaining the hypothalamic-pituitary-adrenal axis in the pituitary, and regulating appetite, energy homeostasis, and body composition in hypothalamic neurons [1]. POMC is also involved in the central melanocortin system, a pathway regulating energy metabolism [2].

Deleting TLR4 in POMC neurons of male mice increases energy expenditure and thermogenesis, reducing body weight, while in female mice, it decreases energy expenditure and increases body weight, affecting white adipose tissue lipolysis [3]. POMC-Cre-mediated Marchf6-deficient mice exhibit hyperphagia, reduced energy expenditure, and weight gain, suggesting Marchf6 is a critical regulator in POMC neurons [4].

In conclusion, POMC is essential for multiple physiological functions including energy metabolism and thermogenesis. Studies using gene-knockout mouse models, like those targeting TLR4 and Marchf6 in POMC neurons, have provided insights into POMC-related metabolic diseases such as obesity, highlighting the importance of POMC in maintaining metabolic homeostasis.