Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China; National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Electronic address: huangzan@njau.edu.cn.
Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, China.
Institute for Health Informatics, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA; College of Medicine, Hunan Normal University, Changsha, Hunan 410081, China.
Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA.
Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China; National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
Institute for Health Informatics, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Clinical Translational Science Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Electronic address: hruan@umn.edu.
Human brown adipose tissue (BAT) undergoes progressive involution. This involution process is not recapitulated in rodents, and the underlying mechanisms are poorly understood. Here we show that the interscapular BAT (iBAT) of rabbits whitens rapidly during early adulthood. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied by loss of brown adipogenic competence of progenitors. Single-cell RNA sequencing reveals that rabbit and human iBAT progenitors highly express the FSTL1 gene. When iBAT involutes in rabbits, adipocyte progenitors reduce FSTL1 expression and are refractory to brown adipogenic recruitment. Conversely, FSTL1 is constitutively expressed in mouse iBAT to sustain WNT signaling and prevent involution. Progenitor incompetence and iBAT paucity can be induced in mice by genetic deletion of the Fstl1 gene or ablation of Fstl1+ progenitors. Our results highlight the hierarchy and dynamics of the BAT progenitor compartment and implicate the functional incompetence of FSTL1-expressing progenitors in BAT involution.
