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There is thus increasing need for human adipocyte models in which to interrogate the function of known and emerging genetic risk variants, yet primary adipocyte cultures, existing immortalised cell lines, and stem-cell based models all have significant biological or practical limitations. In an attempt to widen the repertoire of human cell models in which to study adipocyte-autonomous effects of relevant human genetic variants, we have undertaken direct reprogramming of skin fibroblasts to adipocyte-like cells by employing an inducible recombinant lentivirus overexpressing the master adipogenic transcription factor PPAR\u03b32. Doxycycline-driven expression of PPAR\u03b32 and adipogenic culture conditions converted dermal fibroblasts into triglyceride-laden cells within days. The resulting cells recapitulated most of the critical aspects of adipocyte biology in vivo, including the expression of mature adipocyte markers, secreted high levels of the adipokine adiponectin, and underwent lipolysis when treated with isoproterenol\/IBMX. They did not, however, exhibit insulin-inducible glucose uptake, and withdrawal of doxycycline produced rapid de-lipidation and loss of adipogenic markers. This protocol was applied successfully to a panel of skin cells from individuals with monogenic severe insulin resistance, however, surprisingly, even cell lines harbouring mutations causing severe, generalised lipodystrophy accumulated large lipid droplets and induced adipocyte-specific genes. The direct reprogramming protocol of human dermal fibroblasts to adipocyte-like cells we established is simple, fast and efficient, and has the potential to generate cells which can serve as a tool to address some, though not all, aspects of adipocyte function in the presence of endogenous disease-causing mutations.<\/jats:p>","DOI":"10.1242\/dmm.030981","type":"journal-article","created":{"date-parts":[[2017,10,6]],"date-time":"2017-10-06T00:30:16Z","timestamp":1507249816000},"source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of human dermal fibroblasts directly reprogrammed to adipocyte-like cells as a metabolic disease model"],"prefix":"10.1242","author":[{"given":"Jian-Hua","family":"Chen","sequence":"first","affiliation":[{"name":"The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK"},{"name":"The National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim Jee","family":"Goh","sequence":"additional","affiliation":[{"name":"The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK"},{"name":"The National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno","family":"Rocha","sequence":"additional","affiliation":[{"name":"The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK"},{"name":"The National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3016-4853","authenticated-orcid":false,"given":"Matthijs P.","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK"},{"name":"The National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Minic","sequence":"additional","affiliation":[{"name":"The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK"},{"name":"The National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Barrett","sequence":"additional","affiliation":[{"name":"University of Birmingham, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Savage","sequence":"additional","affiliation":[{"name":"The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK"},{"name":"The National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6539-3069","authenticated-orcid":false,"given":"Robert K.","family":"Semple","sequence":"additional","affiliation":[{"name":"The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK"},{"name":"The National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042513022423100_DMM030981C1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/ncb2411","article-title":"Programming human pluripotent stem cells into white and brown adipocytes","volume":"14","author":"Ahfeldt","year":"2012","journal-title":"Nat. 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