Epigenetic regulation of white adipose tissue plasticity and energy metabolism by nucleosome binding HMGN proteins

• Published in: Nature communications Vol. 13; no. 1; pp. 7303 - 15
• Main Authors: Nanduri, Ravikanth, Furusawa, Takashi, Lobanov, Alexei, He, Bing, Xie, Carol, Dadkhah, Kimia, Kelly, Michael C., Gavrilova, Oksana, Gonzalez, Frank J., Bustin, Michael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/51; 14; 38; 38/88; 38/91; 45/15; 631/337/176; 631/80/304; 64/110; 64/60; Adipocytes; Adipocytes, Brown - metabolism; Adipose tissue; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - metabolism; Animal tissues; Animals; Binding; Body fat; Body weight; Browning; Chromatin; Differentiation; Embryo fibroblasts; Energy balance; Energy expenditure; Energy metabolism; Energy Metabolism - genetics; Enhancers; Epigenesis, Genetic; Epigenetics; Fibroblasts; Fibroblasts - metabolism; Food intake; Gene expression; HMGN Proteins - metabolism; Homeostasis; Humanities and Social Sciences; Male; Males; Metabolism; Mice; multidisciplinary; Nucleosomes - metabolism; Preadipocytes; Proteins; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34964-5

White adipose tissue browning is a key metabolic process controlled by epigenetic factors that facilitate changes in gene expression leading to altered cell identity. We find that male mice lacking the nucleosome binding proteins HMGN1 and HMGN2 (DKO mice), show decreased body weight and inguinal WAT mass, but elevated food intake, WAT browning and energy expenditure. DKO white preadipocytes show reduced chromatin accessibility and lower FRA2 and JUN binding at Pparγ and Pparα promoters. White preadipocytes and mouse embryonic fibroblasts from DKO mice show enhanced rate of differentiation into brown-like adipocytes. Differentiating DKO adipocytes show reduced H3K27ac levels at white adipocyte-specific enhancers but elevated H3K27ac levels at brown adipocyte-specific enhancers, suggesting a faster rate of change in cell identity, from white to brown-like adipocytes. Thus, HMGN proteins function as epigenetic factors that stabilize white adipocyte cell identity, thereby modulating the rate of white adipose tissue browning and affecting energy metabolism in mice. White adipose tissue browning plays an important role in regulating whole-body energy homeostasis and metabolism. Here the authors show that the HMGN nucleosome binding proteins epigenetically promote white adipocyte differentiation and modulate the rate of white adipose tissue browning and energy metabolism in male mice.