title: Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
abstract: White adipose tissue (WAT) morphology characterized by hypertrophy (i.e., fewer but larger adipocytes) associates with increased adipose inflammation, lipolysis, insulin resistance, and risk of diabetes. However, the causal relationships and the mechanisms controlling WAT morphology are unclear. Herein, we identified EBF1 as an adipocyte-expressed transcription factor with decreased expression/activity in WAT hypertrophy. In human adipocytes, the regulatory targets of EBF1 were enriched for genes controlling lipolysis and adipocyte morphology/differentiation, and in both humans and murine models, reduced EBF1 levels associated with increased lipolysis and adipose hypertrophy. Although EBF1 did not affect adipose inflammation, TNFα reduced EBF1 gene expression. High-fat diet intervention in Ebf1(+/-) mice resulted in more pronounced WAT hypertrophy and attenuated insulin sensitivity compared with wild-type littermate controls. We conclude that EBF1 is an important regulator of adipose morphology and fat cell lipolysis and may constitute a link between WAT inflammation, altered lipid metabolism, adipose hypertrophy, and insulin resistance.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mejhert
authors.affiliation: Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Fretz
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden; RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Erik
authors.initials: E
authors.lastname: Arner
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lorente-Cebrián
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ehrlund
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, SE-141 86, Sweden; Science for Life Laboratory, Solna, SE-171 21, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Dahlman-Wright
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Strömblad
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Iyadh
authors.initials: I
authors.lastname: Douagi
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Jurga
authors.initials: J
authors.lastname: Laurencikiene
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, SE-141 86, Sweden; RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Carsten O
authors.initials: CO
authors.lastname: Daub
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
authors.affiliation: Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: mark.horowitz@yale.edu.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Horowitz
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden. Electronic address: peter.arner@ki.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology*; D050154:Adiposity; D000818:Animals; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000473:pathology; D059305:Diet, High-Fat; D005260:Female; D015870:Gene Expression; D006801:Humans; D006984:Hypertrophy; D007249:Inflammation / Q000473:pathology; D007333:Insulin Resistance / Q000502:physiology; D008066:Lipolysis / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034622:RNA Interference; D034741:RNA, Small Interfering; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C081976:EBF1 protein, human; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha