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

Area of Science:

• Reproductive Biology
• Epigenetics
• Metabolic Disorders

Background:

• Obesity is a significant public health issue, linked to metabolic disorders and potentially male infertility.
• Molecular mechanisms underlying obesity's impact on male reproduction are not fully understood.
• Epigenetic modifications, such as histone acetylation, play crucial roles in gene regulation.

Purpose of the Study:

• To investigate the effects of diet-induced obesity on histone acetylation and histone deacetylase (HDAC) expression in mouse testes.
• To explore the molecular link between obesity and male reproductive dysfunction through epigenetic alterations.

Main Methods:

• Male C57BL/6N mice were fed either a control diet or a high-fat diet (HFD) for 8 weeks to induce obesity.
• Testes were analyzed for levels of acetylated histone H3 and H4.
• Expression of histone deacetylase (HDAC) family members was assessed at mRNA and protein levels.

Main Results:

• High-fat diet (HFD) consumption led to decreased acetylation of histone H4 in the testes.
• Histone H3 acetylation levels remained unaffected by the HFD.
• Expression of HDAC8 was significantly upregulated in the testes of HFD-fed mice at both mRNA and protein levels.
• Expression of other class I HDACs (HDAC1, HDAC2, HDAC3) was not altered by HFD exposure.

Conclusions:

• Diet-induced obesity disrupts specific epigenetic features in the male testes, notably reducing histone H4 acetylation.
• Increased expression of HDAC8 appears to be a key mediator of these obesity-induced epigenetic changes.
• These findings provide novel molecular insights into the mechanisms of obesity-related male reproductive dysfunction.