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

In POMC-specific knockout mouse models, deleting TLR4 in POMC neurons modulates brown adipose tissue thermogenesis and lipid homeostasis in a sex-dependent manner. In male mice, it increases energy expenditure and reduces body weight, while in female mice, it decreases energy expenditure and increases body weight [3]. Also, POMC-Cre-mediated Marchf6-deficient mice exhibit hyperphagia, reduced energy expenditure, and weight gain, suggesting that Marchf6 is a critical regulator of metabolic homeostasis in POMC neurons [4].

In conclusion, POMC is essential for multiple physiological functions, especially in energy-related regulations. The study of POMC using KO/CKO mouse models has provided insights into its role in diseases related to energy imbalance, such as obesity and associated metabolic disorders, contributing to a better understanding of the pathophysiology and potential treatment strategies for these conditions.

References:

1. Harno, Erika, Gali Ramamoorthy, Thanuja, Coll, Anthony P, White, Anne. . POMC: The Physiological Power of Hormone Processing. In Physiological reviews, 98, 2381-2430. doi:10.1152/physrev.00024.2017. https://pubmed.ncbi.nlm.nih.gov/30156493/

2. Zhan, Cheng. . POMC Neurons: Feeding, Energy Metabolism, and Beyond. In Advances in experimental medicine and biology, 1090, 17-29. doi:10.1007/978-981-13-1286-1_2. https://pubmed.ncbi.nlm.nih.gov/30390283/

3. Li, Yongxiang, Zhu, Shuqing, Du, Dan, Jiang, Qingyan, Wang, Lina. 2023. TLR4 in POMC neurons regulates thermogenesis in a sex-dependent manner. In Journal of lipid research, 64, 100368. doi:10.1016/j.jlr.2023.100368. https://pubmed.ncbi.nlm.nih.gov/37028769/

4. Mun, Sang-Hyeon, Lee, Chang-Seok, Kim, Hyun Jin, Seong, Je Kyung, Hwang, Cheol-Sang. 2023. Marchf6 E3 ubiquitin ligase critically regulates endoplasmic reticulum stress, ferroptosis, and metabolic homeostasis in POMC neurons. In Cell reports, 42, 112746. doi:10.1016/j.celrep.2023.112746. https://pubmed.ncbi.nlm.nih.gov/37421621/