Hdac3 shapes adipocyte size, death susceptibility, macrophage turnover, and vascular remodeling in a mouse model of obesity
Abstract
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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BibTeX
@article{coppi2026hdac3,
title = {{Hdac3 shapes adipocyte size, death susceptibility, macrophage turnover, and vascular remodeling in a mouse model of obesity}},
author = {Lara Coppi and Ilenia Severi and Fabrizia Bonacina and Sara Villa and Carolina Peri and Raffaella Longo and Martina Senzacqua and Jessica Perugini and Chiara Galli and Silvia Pedretti and Nico Mitro and Alberico Luigi Catapano and Giuseppe Danilo Norata and Antonio Giordano and Emma De Fabiani and Maurizio Crestani},
journal = {Communications Biology},
year = {2026},
month = oct,
doi = {10.1038/s42003-026-11167-y},
url = {https://www.nature.com/articles/s42003-026-11167-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hdac3 shapes adipocyte size, death susceptibility, macrophage turnover, and vascular remodeling in a mouse model of obesity
AU - Lara Coppi
AU - Ilenia Severi
AU - Fabrizia Bonacina
AU - Sara Villa
AU - Carolina Peri
AU - Raffaella Longo
AU - Martina Senzacqua
AU - Jessica Perugini
AU - Chiara Galli
AU - Silvia Pedretti
AU - Nico Mitro
AU - Alberico Luigi Catapano
AU - Giuseppe Danilo Norata
AU - Antonio Giordano
AU - Emma De Fabiani
AU - Maurizio Crestani
PY - 2026
DA - 2026/10/23
JO - Communications Biology
DO - 10.1038/s42003-026-11167-y
UR - https://www.nature.com/articles/s42003-026-11167-y
AB - 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.
SN - 2399-3642
ER -