Chronic high-fat diet decreases global histone H4 acetylation and increases HDAC8 expression in mouse testes.

Obesity is a major public health problem and a risk factor for metabolic disorders, including type 2 diabetes and cardiovascular disease. Additionally, accumulating evidence suggests that obesity impairs male reproductive capacity, potentially leading to infertility. However, molecular insights into the effects of obesity on the male reproductive system remain elusive. In this study, we examined the effects of diet-induced obesity on epigenetic marks-specifically histone acetylation-and the expression of epigenetic regulatory enzymes in mouse testes. C57BL/6 N male mice were randomly divided into two groups: a control group fed a control diet (10% kcal from fat) and a diet-induced obesity group fed a high-fat diet (HFD; 45% kcal from fat) for 8 weeks. Then, the acetylated histone H3 (K9 and K14) and histone H4 (K5, K8, K12, and K16) levels, as well as the expression of the histone deacetylase (HDAC) family, were investigated in the testes. We found that chronic HFD exposure decreased the acetylation levels of histone H4, but not histone H3, in the entire testis. We also observed the increased expression of HDAC8 at both the mRNA and protein levels in the testes of HFD-fed mice. HFD exposure did not affect the expression of other class I HDACs (HDAC1, HDAC2, and HDAC3) in the testes. These findings suggest that HFD-induced obesity disrupts epigenetic features in the testes, specifically through the modulation of HDAC8 and histone H4 acetylation, providing novel insight into obesity-induced male reproductive dysfunction.