Dietary Switch from High Fat Diet to Normal Diet During Early Adulthood Does Not Restore Sperm Quality But Prevents Onset of the Metabolic Syndrome

Abstract

Background: Herein we postulated that high-fat diet (HFD) alters sperm quality and evaluated the effects of switching from a HFD to normal diet in early adulthood on metabolic disease onset, testicular metabolism and sperm quality. Methods: 36 male C57BL6/J mice were divided in a control group fed with standard chow; a group fed with HFD for 200 days; and a group of mice fed initially with HFD for 60 days and then with standard chow (HFDt). Total body weight was monitored and organ weight assessed at sacrifice. Whole-body metabolic function was evaluated by intraperitoneal glucose tolerance test (ipGTT) and intraperitoneal insulin resistance test (ipITT). Epididymal sperm quality was characterised for concentration, motility, viability and morphology. 1H-NMR was performed on testicular extracts to trace the metabolic profile by a metabolomics approach. Findings: Diet switch reduced body weight and the percentage of fat mass, which prevented the metabolic syndrome onset. Sperm quality (viability, motility and head defects) was decreased by HFD consumption and not restored by diet switch. HFD induced irreversible changes in pyruvate and glutamate metabolism, ethanol degradation and ammonia recycling in testis. Furthermore, HFDt changed purine and cysteine metabolism, urea cycle, and glutathione content. Interpretation: HFD causes irreversible changes in testicular metabolism even after switching the diet. HFD feeding until early adulthood decreases sperm quality, which cannot be restored by diet switch or weight loss, even when development of the metabolic syndrome is avoided. Funding Statement: This work was supported by the Portuguese Foundation for Science and Technology: L. Crisostomo (SFRH/BD/128584/2017), M.G. Alves (IFCT2015, PTDC/BIM-MET/4712/2014 and PTDC/MEC-AND/28691/2017), P.F. Oliveira (IFCT2015 and PTDC/BBB-BQB/1368/2014), and UMIB (PestOE/SAL/UI02015/2014) co-funded by FEDER funds (POCI/COMPETE 2020); by the Portuguese Society of Diabetology: L. Crisostomo and M.G. Alves (“Nuno Castel-Branco” research grant); and by the Amadeu Dias Foundation: M.G. Alves and P.F. Oliveira. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The animal model is compliant with the ARRIVE guidelines and was licensed by the Portuguese Veterinarian and Food Department (0421/000/000/2016).