C/EBPβ regulates hypertrophic versus hyperplastic fat tissue growth

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. Obesity further augments the systemic low-grade inflammation that is associated with ageing (inflammaging), which is seen as causal for age-related metabolic decline. Some obese individuals, however, stay metabolically healthy. In these healthy obese individuals, fat is stored in hyperplastic fat tissue that contains an increased number of adipocytes that stay smaller, are metabolically more active and less inflamed. In a previous study we demonstrated that the transcription factor C/EBPβ through differential expression of its protein isoforms LAP and LIP determines health and lifespan in mice. LIP deficient, yet LAP proficient mice, display enhanced fat metabolism under normal feeding conditions. Here we show that under enforced fat storage in mice on a high-fat diet LIP-deficiency results in adipocyte hyperplasia, associated with metabolic and inflammatory improvements. 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.