title: Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling.
abstract: Caloric restriction (CR) extends lifespan from yeast to mammals, delays onset of age-associated diseases, and improves metabolic health. We show that CR stimulates development of functional beige fat within the subcutaneous and visceral adipose tissue, contributing to decreased white fat and adipocyte size in lean C57BL/6 and BALB/c mice kept at room temperature or at thermoneutrality and in obese leptin-deficient mice. These metabolic changes are mediated by increased eosinophil infiltration, type 2 cytokine signaling, and M2 macrophage polarization in fat of CR animals. Suppression of the type 2 signaling, using Il4ra(-/-), Stat6(-/-), or mice transplanted with Stat6(-/-) bone marrow-derived hematopoietic cells, prevents the CR-induced browning and abrogates the subcutaneous fat loss and the metabolic improvements induced by CR. These results provide insights into the overall energy homeostasis during CR, and they suggest beige fat development as a common feature in conditions of negative energy balance.
authors: Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors: Salvatore
authors: S
authors: Fabbiano
authors: Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors: Nicolas
authors: N
authors: Suárez-Zamorano
authors: Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors: Dorothée
authors: D
authors: Rigo
authors: Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors: Christelle
authors: C
authors: Veyrat-Durebex
authors: Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors: Ana
authors: A
authors: Stevanovic Dokic
authors: Centre for BioMedical Imaging (CIBM), University Hospitals of Geneva, 1211 Geneva, Switzerland.
authors: Didier J
authors: DJ
authors: Colin
authors: Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, 1211 Geneva, Switzerland. Electronic address: mirko.trajkovski@unige.ch.
authors: Mirko
authors: M
authors: Trajkovski
mesh_terms: D000069796:Adipose Tissue, Beige / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D004032:Diet; D005247:Feeding Behavior; D005947:Glucose / Q000378:metabolism; D007109:Immunity; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D015398:Signal Transduction / Q000276:immunology*; D050151:Subcutaneous Fat / Q000378:metabolism; D022722:Thermogenesis
chemical_list: D005947:Glucose