Enhanced C/EBPβ function promotes hypertrophic versus hyperplastic fat tissue growth and prevents steatosis in response to high-fat diet feeding

Christine Müller, Laura M. Zidek, Sabrina Eichwald, Gertrud Kortman, Mirjam H. Koster and Cornelis F. Calkhoven

eLife 2022; 11: e62625 DOI: 10.7554/eLife.62625

Obesity is usually characterized by fat accumulation in enlarged – hypertrophic – adipocytes that are a source of inflammatory mediators promoting the development and progression of metabolic disorders. Yet, in certain healthy obese individuals, fat is stored in metabolically more favorable hyperplastic fat tissue that contains an increased number of smaller adipocytes that are less inflamed. Here we show that mice that are genetically modified for C/EBPβ super-function (Cebpb^ΔuORF mice) store fat into hyperplastic adipocytes and that this is associated with reduced inflammation, prevention of steatosis and preservation of glucose metabolism. In males, C/EBPβ super-function also stimulates the favorable storage in subcutaneous fat depots over the less favorable storage in visceral fat depots. Our data identify C/EBPβ as a regulator of adipocyte fate in response to increased fat intake, with major implications for metabolic health and probably aging.