Dietary intervention enhances fertility in obese male mice by regulating SLC2As

Research has demonstrated that obesity can affect male fertility and reproductive potential, but the underlying mechanism remains unclear. This study aimed to investigate the effects of a high-fat diet (HFD) and dietary intervention on reproductive function, glucose metabolism, and related SLC2As in male mice. Forty 4-week-old male ICR mice were randomly divided into the normal diet (ND) group (group N, n = 15) and the HFD group (group F, n = 25). After 12 weeks, the mice were further divided into the following groups: ND maintenance group (NN group, n = 10), HFD maintenance group (FF group, n = 10), and transition to ND group (FN group, n = 10) through dietary intervention for 8 weeks. Intraperitoneal glucose tolerance test (IPGTT) was performed, and parameters including fasting blood glucose, body weight, sperm count, sperm motility, and testis and epididymis measurements were recorded. Testicular morphology was observed through hematoxylin-eosin staining. Western blot and immunofluorescence were used to detect the protein expression and localisation of SLC2As in the testis. Long-term HFD consumption resulted in increased body and testicular weights, decreased testicular and epididymal organ coefficients, reduced sperm motility rate, and increased area under the curve in the IPGTT test. After dietary intervention, compared to the NN group, the FF and FN groups exhibited increased testis weight, decreased testicular and epididymal organ coefficients, decreased sperm motility rate, reduced SLC2A3 and SLC2A8 protein expression levels in the FF group, and decreased SLC2A8 protein expression in the FN group. Obesity induced by HFD caused damage to the reproductive system of male mice and affected testicular glucose metabolism and the expression of sugar transporter SLC2As. Transitioning from HFD to ND can improve reproductive dysfunction caused by dietary obesity and its impact on sugar transporter protein expression to a certain extent.