The role of transcription factors in human brown adipose tissue development

• Applicant: Dr. Daniel Tews
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2015 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 271016542

Upon cold exposure or pharmacological treatment, brown-likeadipocytes can emerge in white adipose tissue (WAT), representinganother phenotype of adipocytes differentiating from a certain subtypeof progenitor cells (Enerback, 2009). Using comparative transcriptomeanalyses of human white and brown adipocyte progenitor cells, weidentified factors which were differentially expressed between thesecell types (Tews et al., 2014). We had hypothesized that thesecandidate genes are involved in the induction of a brown adipocytedifferentiation program in white adipocytes. We could demonstratethat our prime candidate gene Teneurin-2 (TENM2) functions as afactor maintaining the white adipocyte phenotype during adipogenicdifferentiation (Tews et al., 2017). We also show that knockdown offurther candidate genes leads to induction of the brown adipocytespecific gene uncoupling protein 1 (UCP1). In the proposed renewalof this project we will focus on the candidate gene Neuritin-1 (NRN1).Our data demonstrate that knockdown of NRN1 leads to induction ofa brown adipocyte differentiation program in human preadipocytes invitro. We therefore hypothesize that NRN1 ablation induces browningin vivo. To proof our hypothesis, we will investigate whether NRN1deficient mice (Fujino et al., 2011) develop browning of WAT andwhether these animals are resistant to diet-induced obesity and themetabolic syndrome.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Martin Wabitsch