Weiqiang Li, He Gao, Chaowei Zhou, Luo Lei, Junting Li, Chao Ma, Zitu Ma, Mengwei Yao, Kexin Ma, Yunpeng Xiang, Yan Zhou, Yongrui Lu, Da Ji, Minghong Wei, Luohao Xu, Zhaofang Han, Haiping Liu
Adaptive reprogramming to oligotrophic environments is a key evolutionary strategy for extreme-habitat species. While enhanced fat storage and autophagy activation are well-elucidated, the molecular basis of growth retardation remains undefined. The Qinghai-Tibet Plateau shows decreasing nutrient availability with rising elevation, and its endemic Schizopygopsis younghusbandi is an ideal model for nutrient scarcity adaptation. We mimicked nutrient deficiency via in vitro low-serum and in vivo starvation assays, identifying that inhibin βB acts centrally: its upregulation activates the SMAD pathway, inducing G1 phase arrest, attenuated proliferation, and reduced energy consumption. Nutrient deprivation also upregulates pdgf-c to induce a fibrotic phenotype in muscle satellite cells. In vivo assays verified inhibin βB elevation, reversible upon refeeding. We established a S. younghusbandi muscle satellite cell culture system, elucidating inhibin βB-mediated adaptive mechanisms. Comparative sequence analysis across eight Cyprinid species revealed high conservation (>90%) of inhibin βB, suggesting evolutionary preservation. These findings uncover molecular underpinnings of high-altitude schizothoracine adaptive evolution to nutrient scarcity, and broaden insights into survival strategies of organisms in extreme oligotrophic habitats.