Sertoli cell adaptation to glucose deprivation: Potential role of AMPK in the regulation of lipid metabolism

RINDONE, GUSTAVO M.; DASSO, MARINA E.; CENTOLA, CECILIA L.; PELLIZZARI, ELIANA H.; CAMBEROS, MARÍA DEL C.; TONEATTO, JUDITH; GALARDO, MARÍA N.; MERONI, SILVINA B.; RIERA, MARÍA F.

JOURNAL OF CELLULAR BIOCHEMISTRY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2023

0730-2312

Sertoli cells (SCs) provide an adequate environment for germ cell development. SCs possess unique features that meet germ cells´ metabolic demands:they produce lactate from glucose, which is delivered as energy substrate togerm cells. SCs store fatty acids (FAs) as triacylglycerols (TAGs) in lipiddroplets (LDs) and can oxidize FAs to sustain their own energetic demands.They also produce ketone bodies from FAs. It has been shown that exposure ofSCs to metabolic stresses, such as glucose deprivation, triggers specificadaptive responses that sustain cell survival and preserve lactate supply togerm cells. The aim of the present study was to investigate whether there aremodifications in rat SCs lipid metabolism, including LD content, FA oxidation,and ketone bodies production, as part of their adaptive response to glucosedeprivation. The present study was performed in 20‐day‐old rat SCs cultures.We determined LD content by Oil Red O staining, FA oxidation by measuringthe release of 3H2O from [3H] palmitate, TAGs and 3‐hydroxybutyrate levelsby spectrophotometric methods, and mRNA levels by RT‐qPCR. Results showthat the absence of glucose in SC culture medium entails: (1) a decrease in LDcontent and TAGs levels that is accompanied by decreased perilipin 1 mRNAlevels, (2) an increase in FA oxidation that is in part mediated by AMP kinase(AMPK) activation and (3) a decrease in 3‐hydroxybutyrate production.Additionally, we studied whether sestrins (SESN1, 2 and 3), proteins involvedin the cellular response to stress, are regulated in glucose deprivationconditions. We show that there is an increase in SESN2 mRNA levels indeprived conditions. In conclusion, glucose deprivation affects SC lipidmetabolism promoting FA mobilization from LDs to be used as energy source