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Obesity is usually characterized by fat accumulation in enlarged \u2013 hypertrophic \u2013 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\/EBP\u03b2-LIP and the resulting augmented function of the transactivating isoform C\/EBP\u03b2-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\/EBP\u03b2 as a regulator of adipocyte fate in response to increased fat intake, which has major implications for metabolic health and aging.<\/jats:p>","DOI":"10.7554\/elife.62625","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T10:00:21Z","timestamp":1650621621000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.62625","source":"Crossref","is-referenced-by-count":10,"title":["Enhanced C\/EBP\u03b2 function promotes hyperplastic versus hypertrophic fat tissue growth and prevents steatosis in response to high-fat diet feeding"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1974-4053","authenticated-orcid":true,"given":"Christine","family":"M\u00fcller","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012p63287","id-type":"ROR","asserted-by":"publisher"}],"name":"European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen","place":["Groningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M","family":"Zidek","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/039a53269","id-type":"ROR","asserted-by":"publisher"}],"name":"Leibniz Institute on Aging - 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