Cambridge University Stephen O'Rahilly and other researchers mainly analyzed the phenotypes of "mutants" with missing functions of human related proteins and found that MC3R receptors, which are abundantly expressed in hypothalamic nerve cells, can "sense" energy supply status and allocate energy. For growth and reproduction(1).
Researchers found a human "mutant" with homozygous MC3R loss of function that showed reduced muscle proportions. Further combined with UK Biobank data, it was found that heterozygotes with MC3R functional defects manifested as lower height (especially trunk length) , delayed sexual maturity (delayed menarche and voice change) , decreased limb muscle proportion, and insulin-like growth factor 1 (IGF1). secretion is low.
MC3R function-deficient homozygotes have reduced muscle proportion (1)
MC3R function-deficient heterozygotes have growth and reproductive retardation (1)
Further, consistent phenotypes were found in mice with MC3R gene knockout; and interestingly, MC3R gene knockout After removal, the estrous cycle of mice (similar to the human menstrual cycle) is no longer affected by energy restriction; the estrous cycle of wild-type mice is prolonged in a food-deprived state, whereas the basic estrous cycle of MC3R mice remains essentially unchanged. .
MC3R knockout mice's estrous cycle is no longer affected by food supply status (1)
In summary, this work mainly answers the question of how the "energy" obtained by animals is distributed. Researchers suggest that MC3R agonists may alleviate developmental delays, sexual maturation disorders, and even sarcopenia .
This work was published in nature(1) on November 3, 2021.
Comments:
MC3R, the regulatory molecule of "cake distribution", is theoretically a very good intervention site for metabolic regulation; however, its "function enhancement" is often needed and it is difficult to target directly. Perhaps further analysis of its signaling pathway Or developing more selective agonists for MC3R is a feasible direction (2).
Corresponding author introduction:
https://www.mrl.ims.cam.ac.uk/research/principal-investigators/professor-sir-stephen-orahilly/
References:
1. B. Y. H. Lam et al., MC3R nutritional links state to childhood growth and the timing of puberty. Nature, 1–6 (2021).
2. P. Jeffrey Conn, A. Christopoulos, C.W. Lindsley, Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat. Rev . Drug Discov. 2009 81. 8, 41–54(2009).
Original link:
https://www.nature.com/articles/s41586-021-04088-9
