A Comparative Study on the Adverse Effects of a High-Fat Diet on Testicular Tissue: Exploring the Difference Between Obesity-Prone and Obesity-Resistant Mice.

Abstract

The impact of a High-Fat Diet (HFD) on male reproductive health is characterized by fertility disorders in obese males, attributed to oxidative stress, endocrine suppression, and upregulation of pro-apoptotic elements. It remains unclear if observed disorders are primarily linked to obesity or if HFD, independently of obesity, induces similar effects in resistant cases. To explore this subject, immature male mice were divided into control (received a normal diet) and experimental groups. After receiving 16 weeks on the HFD regimen (45%, 4.8 kcal/g), the mice were further categorized into control, obesity-prone (HFD-O, weighting 1.4 times higher than control mice), and obesity-resistant (HFD-OR) groups. The histological characteristics, testicular and serum total antioxidant capacity (TAC), testicular malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), lactate, lactate dehydrogenase (LDL), the expression levels of Bcl-2, BAX, and p53 were analyzed. Current study revealed comparable phenotypes in both HFD-received groups, including histological changes, the relative ratio of TAC to MDA, the GSH to GSSG ratio, serum testosterone levels, lactate and LDH content, as well as several parameters related to sperm quality. Despite these similarities, the obesity-prone (HFD-O) group exhibited increased mRNA and protein levels of BAX and p53, while no significant changes were observed in the obesity-resistant (HFD-OR) mice. In conclusion, in obesity-prone condition, HFD disrupted spermatogenesis through metabolic failure and redox imbalance, which in turn increased pro-apoptotic proteins expression. However, regardless of apoptosis, in obesity-resistant condition, HFD disrupted metabolic processes and endocrine capacity in testicular tissue, hindering spermatogenesis through interference with GSH/GSSG and TAC/MDA relative balances.