Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice.
Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development. However, Prdm16 was required in young mice to suppress the expression of white-fat-selective genes in BAT through recruitment of the histone methyltransferase Ehmt1. Additionally, Prdm16 deficiency caused a severe adult-onset decline in the thermogenic character of interscapular BAT. This resulted in BAT dysfunction and cold sensitivity but did not predispose the animals to obesity. Interestingly, the loss of brown fat identity due to ablation of Prdm16 was accelerated by concurrent deletion of the closely related Prdm3 gene. Together, these results show that Prdm16 and Prdm3 control postnatal BAT identity and function.
Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Matthew J
MJ
Harms
Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Jeff
J
Ishibashi
Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Wenshan
W
Wang
Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Hee-Woong
HW
Lim
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Susumu
S
Goyama
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Tomohiko
T
Sato
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Mineo
M
Kurokawa
Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Kyoung-Jae
KJ
Won
Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA. Electronic address: sealep@upenn.edu.
Patrick
P
Seale
D052437:Adipocytes, Brown / Q000378:metabolism / Q000502:physiology*; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006652:Histological Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C521133:Prdm16 protein, mouse; D014157:Transcription Factors; C513479:GLP protein, mouse; D011495:Histone-Lysine N-Methyltransferase