SUN-216 High Fat Diet Regulate Energy Metabolism of Sertoli Cells

Abstract

The harmfulness of high fat diet (HFD) to male fertility remains conflict. Sertoli cells (SCs) are essential for spermatogenesis as they provide developing germ cells (GCs) with physical support, nutrients and energy (1). Lactate produced by SCs represents as the preferential energy substrate to GCs (2). The aim of this study was to investigate the effects of HFD on energy supply of SCs to GCs and to themselves. In vivo, in order to assess the effects of HFD on male fertility and SCs, male Wistar rats were fed with HFD for 8 weeks. The results showed that the sperm concentration (P<0.01) and pups per litter (7.33 ± 1.20 vs 12.33 ± 0.33,P<0.05) significantly decreased in HFD rats compared to those normal diet (ND) fed rats. Furthermore, the seminiferous epithelia were slightly thinned and disorganized in HFD rats, accompanied by an increased number of vacuoles and lipid droplets in SCs. In vitro, primary SCs obtained from 19-20 days of Wistar male rats were cultured with 0.25 and 0.50 mM palmitic acid for 24 hours for further studies. We firstly assessed the energy supply of SCs to GCs, and found that palmitic acid promoted glycolysis and improved lactate production (P<0.01) and transport by increasing the protein expression or activity associated with lactate biosynthesis and transport. To investigate the effect of palmitic acid on SCs energy metabolism, we assessed mitochondrial function via extracellular flux analyzer. The mitochondrial ATP synthesis (P<0.01) and maximum respiratory capacity (P<0.01) were decreased, while mitochondrial proton leakage was increased in SCs cultured with 0.5mM palmitic acid. Consistent with these, palmitic acid increased mitochondrial ROS and decreased mitochondrial membrane potential. For SCs, fatty acid β-oxidation is suggested to be used to satisfy the vast majority of their own energy needs (3). In this study, compared to control cells, the protein level of β-oxidative Key enzyme, carnitine palmitoyl-transferase 1α in SCs exposed to palmitic acid was decreased (P<0.01), along with the increase of intracellular lipid droplets. In conclusion, palmitic acid increased lactate production. At the same time, palmitic acid also impaired mitochondrial respiratory and fatty acid β-oxidation. We speculate that SCs yields more lactate could not only ensure the energy supply of SCs to GCs under harsh conditions, but also compensate for its own energy metabolism disorder. (1) Mruk DD et al., Endocrine reviews 2004; 25: 747-806. (2) Smith LB et al., Seminars in cell & developmental biology 2014; 30: 2-13. (3) Xionget al., Reproduction 2009 137,469-479