AdipoR2, a member of the seven-transmembrane-domain receptor family, is a receptor for adiponectin, an adipocytokine. It plays a crucial role in regulating glucose and lipid metabolism, and is involved in pathways such as fatty acid oxidation, glucose uptake, and the PI3K-Akt pathway [1,5]. Genetic models, like knockout mouse models, are valuable for studying AdipoR2's functions.

In AdipoR2 knockout mice, the brain is enlarged with cellular membranes overly rich in saturated fatty acids, leading to hyperactivity in older mice [3]. In male meiotic germ cells, AdipoR2 knockout causes membrane stiffening, impairing meiotic telomere distribution, homologous synapsis, recombination, and intercellular bridge formation [4]. In non-alcoholic steatohepatitis (NASH) and liver fibrosis mouse models, an AdipoR1/AdipoR2 dual agonist improves the condition by enhancing the ER-mitochondria axis function [1]. In glioblastoma cell lines, AdipoR2 over-expression induces G0/G1 cell cycle arrest via the AMPK/mTOR pathway [2].

In conclusion, AdipoR2 is essential for maintaining normal membrane fluidity, regulating fatty acid metabolism, and influencing cell cycle progression. Its study through KO mouse models has revealed its significance in diseases such as NASH, liver fibrosis, and glioblastoma, providing potential therapeutic targets for these conditions.

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. Jie, Chen, Xuan, Wang, Feng, Han-Dong, Fei, Sun, Hao, Zhang. 2021. AdipoR2 inhibits human glioblastoma cell growth through the AMPK/mTOR pathway. In European journal of medical research, 26, 28. doi:10.1186/s40001-021-00496-9. https://pubmed.ncbi.nlm.nih.gov/33752745/

3. Ruiz, Mario, Devkota, Ranjan, Bergh, Per-Olof, Borén, Jan, Pilon, Marc. . Aging AdipoR2-deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 38, e23815. doi:10.1096/fj.202400293RR. https://pubmed.ncbi.nlm.nih.gov/38989587/

4. Zhang, Jingjing, Ruiz, Mario, Bergh, Per-Olof, Pilon, Marc, Shibuya, Hiroki. 2024. Regulation of meiotic telomere dynamics through membrane fluidity promoted by AdipoR2-ELOVL2. In Nature communications, 15, 2315. doi:10.1038/s41467-024-46718-6. https://pubmed.ncbi.nlm.nih.gov/38485951/

5. de Oliveira, Cristiane, de Mattos, Ana Barbosa Marcondes, Silva, Carolina Biz Rodrigues, Mota, João Felipe, Zemdegs, Juliane Costa Silva. . Nutritional and hormonal modulation of adiponectin and its receptors adipoR1 and adipoR2. In Vitamins and hormones, 90, 57-94. doi:10.1016/B978-0-12-398313-8.00003-8. https://pubmed.ncbi.nlm.nih.gov/23017712/