Sertoli cell adaptation to glucose deprivation: Potential role of AMPK in the regulation of lipid metabolism
- 22 March 2023
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 124 (5), 716-730
- https://doi.org/10.1002/jcb.30399
Abstract
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 to germ cells. SCs store fatty acids (FAs) as triacylglycerols (TAGs) in lipid droplets (LDs) and can oxidize FAs to sustain their own energetic demands. They also produce ketone bodies from FAs. It has been shown that exposure of SCs to metabolic stresses, such as glucose deprivation, triggers specific adaptive responses that sustain cell survival and preserve lactate supply to germ cells. The aim of the present study was to investigate whether there are modifications in rat SCs lipid metabolism, including LD content, FA oxidation, and ketone bodies production, as part of their adaptive response to glucose deprivation. The present study was performed in 20-day-old rat SCs cultures. We determined LD content by Oil Red O staining, FA oxidation by measuring the release of (H2O)-H-3 from [H-3] palmitate, TAGs and 3-hydroxybutyrate levels by spectrophotometric methods, and mRNA levels by RT-qPCR. Results show that the absence of glucose in SC culture medium entails: (1) a decrease in LD content and TAGs levels that is accompanied by decreased perilipin 1 mRNA levels, (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 involved in the cellular response to stress, are regulated in glucose deprivation conditions. We show that there is an increase in SESN2 mRNA levels in deprived conditions. In conclusion, glucose deprivation affects SC lipid metabolism promoting FA mobilization from LDs to be used as energy source.Keywords
Funding Information
- Consejo Nacional de Investigaciones Científicas y Técnicas (PIP2021/162)
- Agencia Nacional de Promoción Científica y Tecnológica (PICT 2018/1291, PICT 2018/1973, PICT 2020/0642)
This publication has 44 references indexed in Scilit:
- The monocarboxylate transporter family—Structure and functional characterizationIUBMB Life, 2011
- LKB1 and AMP‐activated protein kinase control of mTOR signalling and growthActa Physiologica, 2009
- Autophagy regulates lipid metabolismNature, 2009
- Apoptotic spermatogenic cells can be energy sources for Sertoli cellsReproduction, 2009
- Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1αThe EMBO Journal, 2007
- Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinaseBiochemical Society Transactions, 2002
- Regulation of rat Sertoli cell function by FSH: possible role of phosphatidylinositol 3-kinase/protein kinase B pathwayJournal of Endocrinology, 2002
- Is there an astrocyte–neuron ketone body shuttle?Trends in Endocrinology & Metabolism, 2001
- REGULATION OF FATTY ACID OXIDATION IN SKELETAL MUSCLEAnnual Review of Nutrition, 1999
- Physiological Effect of Glucagon in Human Isolated AdipocytesHormone and Metabolic Research, 1995