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

• Published in: eLife 2022-04, Vol.11
• Main Authors: Müller, Christine, Zidek, Laura M, Eichwald, Sabrina, Kortman, Gertrud, Koster, Mirjam H, Calkhoven, Cornelis F
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Animals; Diet, High-Fat - adverse effects; Fatty Liver - metabolism; Hyperplasia - metabolism; Hypertrophy; Male; Mice; Obesity - metabolism; Protein Isoforms - metabolism
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.62625

Chronic obesity is correlated with severe metabolic and cardiovascular diseases as well as with an increased risk for developing cancers. Obesity is usually characterized by fat accumulation in enlarged - hypertrophic - adipocytes that are a source of inflammatory mediators, which promote 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. In a previous study, we demonstrated that loss of the inhibitory protein-isoform C/EBPβ-LIP and the resulting augmented function of the transactivating isoform C/EBPβ-LAP promotes fat metabolism under normal feeding conditions and expands health- and lifespan in mice. Here, we show that in mice on a high-fat diet, LIP-deficiency results in adipocyte hyperplasia associated with reduced inflammation and metabolic improvements. Furthermore, fat storage in subcutaneous depots is significantly enhanced specifically in LIP-deficient male mice. Our data identify C/EBPβ as a regulator of adipocyte fate in response to increased fat intake, which has major implications for metabolic health and aging.