Differential expression of sirtuin 2 and adipocyte maturation restriction: an adaptation process during hypoxia in fish [RESEARCH ARTICLE]

Padmini Ekambaram and Parimala Parasuraman

Sirtuins have received widespread attention due to their diverse physiological role in metabolism. Among sirtuins, SIRT2 is more abundant in adipocytes and exerts effects on adipocyte differentiation, a process which involves conversion of preadipocytes to mature adipocytes orchestrated by adipokines and adipogenic transcription factors. Grey mullet (Mugil cephalus) was chosen as a study organism due to its excellent service as a biomonitor. Adipocytes isolated from natural field conditions were termed as field-hypoxic (Ennore) and -normoxic (Kovalam) based on dissolved oxygen (DO) level in the estuary. A previous study portrayed the hypoxic instance of Ennore estuary (low DO) and grey mullet [HIF1α in adipocytes, brain endothelial cell (EC) and hepatocytes] inhabiting this estuary ( Padmini et al., 2016a, b; Padmini and Tharani, 2015). In this context, fish adipocytes of both conditions were subjected to in vitro hypoxia for 1 h (in the pre/trigassed incubator with the supply of 1% O₂; 94% N₂; 5% CO₂) and were analysed for the expression of adipokines, adipogenic transcription factors and anti-adipogenic markers in fish adipocytes. Elevation of asymmetric dimethylarginine (ADMA), TNFα and leptin along with decreased adiponectin, adipogenic transcription factors and altering sirtuins were observed in test adipocytes and in control adipocytes on in vitro hypoxia. This suggests that adipocytes may follow internal caloric restriction as portrayed from cytomorphological/ultrastructural analysis, limiting adipocyte maturation process, one of the adaptive mechanisms triggered by adipocyte of fish surviving in Ennore estuary. Prolonged exposure to hypoxia (test on in vitro hypoxia for 1 h) showed a drastic alteration in these components leading to both structural and biological fluctuation when compared to limited hypoxic condition (field-hypoxic and control on in vitro hypoxia). Our study concludes that hypoxia may serve as the chief molecular cue in eliciting adipocyte maturation restriction though metabolic reprogramming and it also shows the significance of adipocyte maturation restriction in imparting survival mechanism.

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