Key result
Adipocyte Hdac3 deletion reduces visceral fat mass and adipocyte size while enhancing vascularization in mice.
Why the study?
The crosstalk between adipocytes and macrophages is crucial in adipose tissue biology, motivating an investigation into the role of adipocyte-expressed histone deacetylase 3 (Hdac3) on adipose tissue plasticity and immune cell composition in response to high-fat feeding.
Does adipocyte-specific Hdac3 inactivation affect adipose tissue plasticity, vascular remodeling, macrophage turnover, and cell death susceptibility in a mouse model of diet-induced obesity?
Does adipocyte-specific Hdac3 inactivation affect adipose tissue plasticity, vascular remodeling, macrophage turnover, and cell death susceptibility in a mouse model of diet-induced obesity?
In a mouse model of obesity, adipocyte-expressed Hdac3 acts as a rheostat in visceral fat by regulating lipid accumulation and adipocyte hypertrophy while limiting adipocyte death, angiogenesis, and local macrophage proliferation, without altering systemic glucose tolerance or insulin sensitivity.
May inform adipocyte-targeted obesity therapies; leaves open translation from mouse models to human visceral fat.
The crosstalk between adipocytes and macrophages is crucial in adipose tissue biology. The aim of this study was to investigate the role of adipocyte-expressed histone deacetylase 3 (Hdac3) on adipose tissue plasticity and immune cell composition in response to high-fat feeding. Here we show that adipocyte-specific deletion of Hdac3 gene in mice affects the response to high-fat overload, by reducing fat mass and adipocyte size in visceral fat of knockout mice. In the absence of adipocyte Hdac3, visceral fat shows vascular remodeling and increased macrophage content. Colocalization of F4/80 with Ki-67 indicates proliferation of resident macrophages. This is coupled with increased crown-like structures and adipocyte death in visceral fat of knockout mice, exacerbated by high-fat feeding. Hdac3 silencing in cultured adipocytes and inactivation in mice promotes a pro-apoptotic microenvironment, as assessed by positivity to Annexin V and cleaved Caspase 3. In conclusion, we propose that Hdac3 acts as a rheostat in visceral fat, differentially affecting lipid accumulation and adipocyte size during the progress of high fat diet (HFD) feeding, and limiting cell death, vascularization, and macrophage proliferation, in a mouse model of obesity.
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Coppi et al. (2026) studied Diet-induced obesity (preclinical mouse model). Adipocyte-specific Hdac3 gene deletion (H3fatKO) and high-fat diet feeding vs. Floxed control mice and low-fat diet was evaluated on Visceral white adipose tissue (eWAT) plasticity, adipocyte size, macrophage proliferation, and apoptosis susceptibility. Adipocyte-specific Hdac3 deletion in high-fat fed mice reduced visceral fat mass and adipocyte size while increasing vascularization, macrophage proliferation, and apoptosis.
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