Dandan Luo1, Meijie Zhang2, Xiaohui Su3, Luna Liu2, Xinli Zhou4, Xiujuan Zhang4, Dongmei Zheng4, Chunxiao Yu5, Qingbo Guan6. 1. Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong, China. 2. Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China. 3. Department of Geratology, Jinan People's Hospital Affiliated to Shandong First Medical University, China. 4. Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China; Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China. 5. Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong, China; Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China. Electronic address: yuchx08@163.com. 6. Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong, China; Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China. Electronic address: doctorguanqingbo@163.com.
Abstract
AIMS: Sertoli cells (SCs) play an important role in the process of spermatogenesis. SCs provide energy for germ cells (GCs) and themselves through glycolysis and fatty acid oxidation (FAO) respectively. High fat diet (HFD) impairs spermatogenesis by damaging function of SCs, however whether HFD disrupts energy metabolism in SCs remains unclear. MAIN METHODS: To explore this hypothesis, we built male Wistar rat model fed on HFD and cultured rats' primary SCs with palmitic acid (PA). Rats' fertility and sperm quality were evaluated in vivo. Glycolysis, lactate production and mitochondrial respiration were assessed by using extracellular flux analyzer, and the expression of enzymes involved in glucose and FAO was analyzed by Real-Time PCR or Western Blotting. KEY FINDINGS: The showed that the sperm concentration and pups per litter significantly decreased in rats fed on HFD compared to those rats fed on normal diet. There was an elevation of lactate levels in testicular tissue of rats fed on HFD and primary SCs exposed to PA. In vitro, PA increased glycolytic flux, and lactate production, and the levels of carnitine palmitoyltransferase I (CPT1) and long chain acyl-CoA dehydrogenase (LCAD) which were two key enzymes for fatty acid β oxidation. Further analysis showed that mitochondrial respiration was impaired by PA, followed by the decrease in ATP turnover, maximal respiration and the increase in proton leak. SIGNIFICANCE: Taken together, the elevated lactate level, lipid metabolism disorder and mitochondrial dysfunction caused by HFD lead to SCs dysfunction, which ultimately leads to decreased sperm quality.
AIMS: Sertoli cells (SCs) play an important role in the process of spermatogenesis. SCs provide energy for germ cells (GCs) and themselves through glycolysis and fatty acid oxidation (FAO) respectively. High fat diet (HFD) impairs spermatogenesis by damaging function of SCs, however whether HFD disrupts energy metabolism in SCs remains unclear. MAIN METHODS: To explore this hypothesis, we built male Wistar rat model fed on HFD and cultured rats' primary SCs with palmitic acid (PA). Rats' fertility and sperm quality were evaluated in vivo. Glycolysis, lactate production and mitochondrial respiration were assessed by using extracellular flux analyzer, and the expression of enzymes involved in glucose and FAO was analyzed by Real-Time PCR or Western Blotting. KEY FINDINGS: The showed that the sperm concentration and pups per litter significantly decreased in rats fed on HFD compared to those rats fed on normal diet. There was an elevation of lactate levels in testicular tissue of rats fed on HFD and primary SCs exposed to PA. In vitro, PA increased glycolytic flux, and lactate production, and the levels of carnitine palmitoyltransferase I (CPT1) and long chain acyl-CoA dehydrogenase (LCAD) which were two key enzymes for fatty acid β oxidation. Further analysis showed that mitochondrial respiration was impaired by PA, followed by the decrease in ATP turnover, maximal respiration and the increase in proton leak. SIGNIFICANCE: Taken together, the elevated lactate level, lipid metabolism disorder and mitochondrial dysfunction caused by HFD lead to SCs dysfunction, which ultimately leads to decreased sperm quality.