PPARγ activation regulates lipid droplet formation and lactate production in rat Sertoli cells
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Sertoli cells provide the structural and nutritional support for germ cell development; they actively metabolize glucose and convert it to lactate, which is an important source of energy for germ cells. Furthermore, Sertoli cells can oxidize fatty acids, a metabolic process that is assumed to fulfill their own energy requirements. Fatty acids are stored as triacylglycerides within lipid droplets. The regulation of fatty acid storage in conjunction with the regulation of lactate production may thus be relevant to seminiferous tubule physiology. Our aim is to evaluate a possible means of regulation by the PPARγ activation of lipid droplet formation and lactate production. Sertoli cell cultures obtained from 20-day-old rats were incubated with Rosiglitazone (10 μM), a PPARγ activator, for various periods of time (6, 12, 24 and 48 h). Increased triacylglycerides levels and lipid droplet content were observed, accompanied by a rise in the expression of genes for proteins involved in fatty acid storage, such as the fatty acid transporter Cd36, glycerol-3-phosphate-acyltransferases 1 and 3, diacylglycerol acyltransferase 1 and perilipins 1, 2 and 3, all proteins that participate in lipid droplet formation and stabilization. However, PPARγ activation increased lactate production, accompanied by an augmentation in glucose uptake and Glut2 expression. These results taken together suggest that PPARγ activation in Sertoli cells participates in the regulation of lipid storage and lactate production thereby ensuring simultaneously the energetic metabolism for the Sertoli and germ cells.
KeywordsPPARγ Sertoli cells Lipid droplets Lactate Perilipins
The technical help of Mercedes Astarloa is gratefully acknowledged. We also thank Celia Nieto for revising our English usage. This work was supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT) (PICT 2014/945) and the Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET) (PIP 2011/187). M.F. Riera, M.N. Galardo and S.B. Meroni are established investigators of CONICET. A. Gorga is a recipient of an ANPCYT fellowship. G.M. Rindone and M. Regueira are recipients of CONICET fellowships.
- Bosma M, Dapito DH, Drosatos-Tampakaki Z, Huiping-Son N, Huang LS, Kersten S, Drosatos K, Goldberg IJ (2014) Sequestration of fatty acids in triglycerides prevents endoplasmic reticulum stress in an in vitro model of cardiomyocyte lipotoxicity. Biochim Biophys Acta 1841:1648–1655CrossRefPubMedPubMedCentralGoogle Scholar
- Cases S, Smith SJ, Zheng YW, Myers HM, Lear SR, Sande E, Novak S, Collins C, Welch CB, Lusis AJ, Erickson SK, Farese RV Jr (1998) Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc Natl Acad Sci U S A 95:13018–13023CrossRefPubMedPubMedCentralGoogle Scholar
- Cha BS, Ciaraldi TP, Carter L, Nikoulina SE, Mudaliar S, Mukherjee R, Paterniti JR Jr, Henry RR (2001) Peroxisome proliferator-activated receptor (PPAR) gamma and retinoid X receptor (RXR) agonists have complementary effects on glucose and lipid metabolism in human skeletal muscle. Diabetologia 44:444–452CrossRefPubMedGoogle Scholar
- Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK, Gonzalez FJ, Grimaldi PA, Kadowaki T, Lazar MA, O’Rahilly S, Palmer CN, Plutzky J, Reddy JK, Spiegelman BM, Staels B, Wahli W (2006) International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 58:726–741CrossRefPubMedGoogle Scholar
- Oliveira PF, Alves MG, Rato L, Laurentino S, Silva J, Sa R, Barros A, Sousa M, Carvalho RA, Cavaco JE, Socorro S (2012) Effect of insulin deprivation on metabolism and metabolism-associated gene transcript levels of in vitro cultured human Sertoli cells. Biochim Biophys Acta 1820:84–89CrossRefPubMedGoogle Scholar
- Riera MF, Meroni SB, Schteingart HF, Pellizzari EH, Cigorraga SB (2002) Regulation of lactate production and glucose transport as well as of glucose transporter 1 and lactate dehydrogenase a mRNA levels by basic fibroblast growth factor in rat Sertoli cells. J Endocrinol 173:335–343CrossRefPubMedGoogle Scholar
- Zhang B, Szalkowski D, Diaz E, Hayes N, Smith R, Berger J (1994) Potentiation of insulin stimulation of phosphatidylinositol 3-kinase by thiazolidinedione-derived antidiabetic agents in Chinese hamster ovary cells expressing human insulin receptors and L6 myotubes. J Biol Chem 269:25735–25741PubMedGoogle Scholar