Atlas of metabolism reveals palmitic acid results in mitochondrial dysfunction and cell apoptosis by inhibiting fatty acid β-oxidation in Sertoli cells

Abstract

In recent years, the impact of lipotoxicity on male fertility has received extensive attention, especially on Sertoli cells (SCs). In SCs, energy metabolism is important as disorders of energy metabolism result in infertility eventually. However, the underlying mechanism of lipotoxicity on energy metabolism in SCs remains unknown. Advances in high-throughput metabolomics and lipidomics measurement platforms provide powerful tools to gain insights into complex biological systems. Here, we aimed to explore the potential molecular mechanisms of palmitic acid (PA) regulating energy metabolism in SCs based on metabolomics and lipidomics. The results showed that glucose metabolism-related metabolites were not significantly changed, which suggested that PA treatment had little effect on glucose metabolism and may not influence the normal energy supply from SCs to germ cells. However, fatty acid β-oxidation was inhibited according to accumulation of medium- and long-chain acylcarnitines in cells. In addition, the pool of amino acids and the levels of most individual amino acids involved in the tricarboxylic acid (TCA) cycle were not changed after PA treatment in SCs. Moreover, PA treatment of SCs significantly altered the lipidome, including significant decreases in cardiolipin and glycolipids as well as remarkable increases in ceramide and lysophospholipids, which indicated that mitochondrial function was affected and apoptosis was triggered. The increased apoptosis rate of SCs was verified by elevated protein expression levels of Cleaved Caspase-3 and Bax as well as decreased Bcl-2 protein expression level. Together, these findings indicated that PA may result in mitochondrial dysfunction and increased apoptosis by inhibiting fatty acid β-oxidation of SCs.

Chlorogenic Acid from Burdock Roots Ameliorates Oleic Acid-Induced Steatosis in HepG2 Cells through AMPK/ACC/CPT-1 Pathway

“…Normally, triglycerides transported to the liver are broken down into fatty acids and form acyl-coenzyme A, which is transferred to the mitochondria by CPT-1 [28]. The β-oxidation of fatty acids occurs in mitochondria, and breaks down the fatty acids into H 2 O and acetyl-CoA, which are involved in the tricarboxylic acid cycle to provide energy [29]. This is an important process in fat metabolism, and the ability of fatty acid β-oxidation affects triglyceride accumulation in the liver [30].…”

Heat stress releases arachidonic acid to induce autophagy in Sertoli cells by enhancing ROS-mitochondrial-endoplasmic reticulum stress axis

“…4G-H). This is because that AA caused mitochondrial dysfunction and ERS by inhibiting fatty acid β-oxidation in the mitochondria, while promoting lipid peroxidation in the SCs (Xu et al, 2022).…”

Associations Among Microvascular Dysfunction, Fatty Acid Metabolism, and Diabetes

“…Diabetes mellitus involves complex mechanisms leading to dysfunctional fatty acid metabolism, encompassing multiple interconnected factors [11,12]. A critical element is the disruption of fatty acid oxidative metabolism.…”