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Hypoxia coordinates adipocyte hypertrophy andhyperplasia through HlF1aa-ATGL-PPARy pathway enablesrapid and healthy energy storage in grass carp


ABSTRACT: Animals often face food scarcity in nature. In order to survive, some animals store substantial fat when food is available. However, the physiological mechanism by which they store substantial fat and maintain metabolic health in the short term is poorly understood. Here, using the grass carp (Ctenopharyngodon idellus) as a model, which exhibits remarkable fat storage capacity, we found that adipose tissue responded to energy overload first and expanded through adipocyte hypertrophy and hyperplasia. Mechanistically, hypoxia inducible factor-1αa (hif-1αa) was activated in mature adipocytes after short-term high-energy intake, thereby bidirectionally regulating adipose triglyceride lipase (atgl) to drive healthy expansion of adipose tissue in grass carp: (1) Hif-1αa downregulates atgl protein levels via the ubiquitin-proteasome pathway, promoting adipocyte hypertrophy; (2) Hif-1αa upregulates atgl transcription to sustain basal lipolysis, releasing free fatty acids that activate peroxisome proliferator-activated receptor γ (pparγ) in preadipocytes to promote adipocyte hyperplasia. This crosstalk-mediated rapid adipocyte hyperplasia prevents detrimental excessive hypertrophy and significantly boosts the overall energy storage capacity. Taken together, our study reveals how grass carp utilize hypoxia signals (a signal often associated with metabolic disorders in mammals) to coordinate the pattern of adipose tissue expansion, achieving rapid and healthy lipid storage. Our findings redefine hypoxia's role as a metabolic orchestrator rather than a stress indicator, suggesting potential implications for a theoretical basis for addressing obesity-related diseases in humans and farmed animals caused by excessive energy intake.

ORGANISM(S): Ctenopharyngodon idella

PROVIDER: GSE315218 | GEO | 2026/03/04

REPOSITORIES: GEO

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