Histone deacetylases (HDACs) are enzymes that regulate protein functions by catalyzing the removal of acetyl and acyl groups from lysine residues. They play pivotal roles in governing cell behaviors and are indispensable in numerous biological processes. HDAC11, the last identified and sole member of class IV HDACs, was reported over a decade ago. However, its physiological function remains poorly understood. Here, we report that HDAC11 knockout mice are resistant to high-fat diet-induced obesity and metabolic syndrome, suggesting that HDAC11 functions as a crucial metabolic regulator. Depletion of HDAC11 significantly enhanced insulin sensitivity and glucose tolerance, attenuated hypercholesterolemia, and decreased hepatosteatosis and liver damage. Mechanistically, HDAC11 deficiency boosts energy expenditure through promoting thermogenic capacity, which attributes to the elevation of uncoupling protein 1 (UCP1) expression and activity in brown adipose tissue. Moreover, loss of HDAC11 activates the adiponectin-AdipoR-AMPK pathway in the liver, which may contribute to a reversal in hepatosteatosis. Overall, our findings distinguish HDAC11 as a novel regulator of obesity, with potentially important implications for obesity-related disease treatment.

Background:The DNA mismatch repair protein MutS homolog 2 (MSH2) is an acetylated protein.Results: Histone deacetylase 10 (HDAC10) interacts with MSH2 and deacetylates MSH2 at Lys-73, which might stimulate MSH2 activity. Conclusion: HDAC10 promotes DNA mismatch repair activity and may involve the deacetylation of MSH2. Significance: HDAC10 has an important role in regulating DNA mismatch repair.

In an animal model for multiple sclerosis, the absence of HDAC11 reduces clinical severity, spinal cord demyelination, and immune cell infiltration, suggesting that HDAC11 is a promising target for MS treatment.

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