KDM4B protects against obesity and metabolic dysfunction

Significance Obesity has become a major epidemic around the globe, with fatal comorbidities such as type 2 diabetes, heart disease, and cancer that have led to alarming health concerns in modern medicine. Although excess adipose tissue is associated with negative metabolic outcomes, the physiological functions of epigenetic regulators in adipose tissue and metabolism are unclear. Here we show that KDM4B in adipose tissues epigenetically controls energy expenditure, oxidation, lipolysis, and thermogenesis. Loss ofKdm4b impairs energy expenditure, adaptive thermogenesis, and adipose tissue lipolysis, resulting in obesity and associated metabolic dysfunction. Our results provide insights into control of obesity and suggest that modulation of KDM4B levels or activity may be a potential therapeutic target for human obesity.