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

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.