AdipoR1, the receptor of adiponectin, is crucial in regulating various physiological functions. It is involved in initiating signal transduction events like the phosphorylation of adenosine monophosphate (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK) upon binding to adiponectin [2]. This receptor also participates in multiple biological processes such as glucose and lipid metabolism, anti-inflammation, and energy homeostasis regulation [1,2]. Gene knockout (KO) mouse models are valuable for studying AdipoR1's functions.

In AdipoR1 knockout male mice, sperm count, sperm motility, and sperm fertilizing ability were significantly decreased, along with reduced phosphorylation of AMPK and increased expression of pro-apoptotic genes and proteins in the testis, indicating its role in male fertility [5]. In HCC cells, knockdown of AdipoR1 enhanced radiation-induced cell death, DNA damage, and apoptosis, and inhibited cell cycle arrest and autophagy, suggesting its influence on radiation sensitivity [3]. Additionally, AdipoR1 knockdown increased both ionizing radiation-and erastin-induced ferroptosis in HCC cells, mediated by the AdipoR1-Nrf2-xCT pathway [4].

In conclusion, AdipoR1 is essential for maintaining normal physiological functions in processes like metabolism, inflammation, and male fertility. KO mouse models have revealed its significance in male infertility and radiation-related responses in HCC cells. Understanding AdipoR1's functions can potentially provide new therapeutic strategies for related diseases.

References:

1. Xu, Hongjiao, Zhao, Qian, Song, Nazi, Wang, Rui, Jiang, Xianxing. 2020. AdipoR1/AdipoR2 dual agonist recovers nonalcoholic steatohepatitis and related fibrosis via endoplasmic reticulum-mitochondria axis. In Nature communications, 11, 5807. doi:10.1038/s41467-020-19668-y. https://pubmed.ncbi.nlm.nih.gov/33199780/

2. Fang, Han, Judd, Robert L. 2018. Adiponectin Regulation and Function. In Comprehensive Physiology, 8, 1031-1063. doi:10.1002/cphy.c170046. https://pubmed.ncbi.nlm.nih.gov/29978896/

3. Liu, Yi, Qi, Mu, Liu, Lianchang, Ma, Shumei, Liu, Xiaodong. 2022. Blocking Adipor1 enhances radiation sensitivity in Hepatoma Carcinoma Cells. In Archives of biochemistry and biophysics, 718, 109152. doi:10.1016/j.abb.2022.109152. https://pubmed.ncbi.nlm.nih.gov/35183544/

4. Feng, Hao, Liu, Yi, Gan, Yuhan, Liu, Xiaodong, Ma, Shumei. 2022. AdipoR1 Regulates Ionizing Radiation-Induced Ferroptosis in HCC cells through Nrf2/xCT Pathway. In Oxidative medicine and cellular longevity, 2022, 8091464. doi:10.1155/2022/8091464. https://pubmed.ncbi.nlm.nih.gov/35733794/

5. Kobori, Toshiko, Iwabu, Masato, Okada-Iwabu, Miki, Yamauchi, Toshimasa, Kasuga, Masato. 2024. Decreased AdipoR1 signaling and its implications for obesity-induced male infertility. In Scientific reports, 14, 5701. doi:10.1038/s41598-024-56290-0. https://pubmed.ncbi.nlm.nih.gov/38459078/