Early B Cell Factor Activity Controls Developmental and Adaptive Thermogenic Gene Programming in Adipocytes
العنوان: | Early B Cell Factor Activity Controls Developmental and Adaptive Thermogenic Gene Programming in Adipocytes |
---|---|
المؤلفون: | Paul M. Titchenell, Patrick Seale, Jeff Ishibashi, Suzanne N. Shapira, Mitchell A. Lazar, Anthony R. Angueira, Hee-Woong Lim, Matthew J. Emmett, Samay Sampat, Jaimarie Sostre-Colón |
المصدر: | Cell Reports, Vol 30, Iss 9, Pp 2869-2878.e4 (2020) Cell reports |
بيانات النشر: | Elsevier, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | 0301 basic medicine, Transcription, Genetic, Mutant, Regulator, Biology, Diet, High-Fat, Article, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Adipose Tissue, Brown, Brown adipose tissue, Basic Helix-Loop-Helix Transcription Factors, medicine, Animals, Enhancer, Transcription factor, Gene, lcsh:QH301-705.5, Uncoupling Protein 1, B cell, Base Sequence, Thermogenesis, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Cell biology, Cold Temperature, Adipocytes, Brown, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, Receptors, Estrogen, lcsh:Biology (General), NIH 3T3 Cells, 030217 neurology & neurosurgery |
الوصف: | SUMMARY Brown adipose tissue (BAT) activity protects animals against hypothermia and represents a potential therapeutic target to combat obesity. The transcription factor early B cell factor-2 (EBF2) promotes brown adipocyte differentiation, but its roles in maintaining brown adipocyte fate and in stimulating BAT recruitment during cold exposure were unknown. We find that the deletion of Ebf2 in adipocytes of mice ablates BAT character and function, resulting in cold intolerance. Unexpectedly, prolonged exposure to cold restores the thermogenic profile and function of Ebf2 mutant BAT. Enhancer profiling and genetic assays identified EBF1 as a candidate regulator of the cold response in BAT. Adipocyte-specific deletion of both Ebf1 and Ebf2 abolishes BAT recruitment during chronic cold exposure. Mechanistically, EBF1 and EBF2 promote thermogenic gene transcription through increasing the expression and activity of ERRα and PGC1α. Together, these studies demonstrate that EBF proteins specify the developmental fate and control the adaptive cold response of brown adipocytes. Graphical Abstract In Brief Angueira et al. show that early B cell factors (EBFs) control both basal and cold-induced thermogenic activity in brown adipocytes. EBF2 is required to maintain BAT fate under basal conditions, ensuring a capacity for thermogenesis upon cold challenge. BAT recruitment during chronic cold exposure requires EBF1 or EBF2 activity. |
اللغة: | English |
تدمد: | 2211-1247 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0caa3320a252bbdbc20186ebd9563631 http://www.sciencedirect.com/science/article/pii/S2211124720301777 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....0caa3320a252bbdbc20186ebd9563631 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 22111247 |
---|