Key result
Overexpression of constitutively active HDAC4 in adipocytes led to beige adipocyte expansion, increased energy expenditure, and reduced adiposity in mice under normal and high-fat diets.
Why the study?
Does adipocyte HDAC4 activation prevent high-fat diet-induced obesity in mice?
Does adipocyte HDAC4 activation prevent high-fat diet-induced obesity in mice?
Adipocyte HDAC4 activation drives beige adipocyte expansion, which protects mice against high-fat diet-induced obesity, suggesting a potential therapeutic target for obesity.
Adipocyte HDAC4 activation may protect against diet-induced obesity in mice; leaves open human therapeutic translation.
Numerous studies have suggested that beige adipocyte abundance is correlated with improved metabolic performance, but direct evidence showing that beige adipocyte expansion protects animals from the development of obesity is missing. Previously, we have described that the liver kinase b1 (LKB1) regulates beige adipocyte renaissance in subcutaneous inguinal white adipose tissue (iWAT) through a class IIa histone deacetylase 4 (HDAC4)-dependent mechanism. This study investigates the physiological impact of persistent beige adipocyte renaissance in energy homeostasis in mice. Here we present that the transgenic mice H4-TG, overexpressing constitutively active HDAC4 in adipocytes, showed beige adipocyte expansion in iWAT at room temperature. H4-TG mice exhibited increased energy expenditure due to beige adipocyte expansion. They also exhibited reduced adiposity under both normal chow and high-fat diet (HFD) feeding conditions. Specific ablation of beige adipocytes reversed the protection against HFD-induced obesity in H4-TG mice. Taken together, our results directly demonstrate that beige adipocyte expansion regulates adiposity in mice and targeting beige adipocyte renaissance may present a novel strategy to tackle obesity in humans.
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Paulo et al. (2018) studied Obesity. Overexpression of constitutively active HDAC4 in adipocytes (H4-TG mice) vs. Wild-type mice (implied) was evaluated on Adiposity and energy expenditure. Overexpression of constitutively active HDAC4 in adipocytes led to beige adipocyte expansion, increased energy expenditure, and reduced adiposity in mice under normal and high-fat diets.
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