title: EndoG Knockout Mice Show Increased Brown Adipocyte Recruitment in White Adipose Tissue and Improved Glucose Homeostasis.
abstract: Brown adipose tissue (BAT) plays a central role in the regulation of whole-body energy and glucose homeostasis owing to its elevated capacity for lipid and glucose oxidation. The BAT thermogenic function, which is essential for the defense of body temperature against exposure to low environmental temperatures, relies on the expression in the inner membrane of brown adipocyte's mitochondria of uncoupling protein-1, a protein that uncouples substrate oxidation from oxidative phosphorylation and leads to the production of heat instead of ATP. BAT thermogenesis depends on proper mitochondrial biogenesis during the differentiation of brown adipocytes. Despite the data that support a role for Endonuclease G (EndoG) in the process of mitochondrial biogenesis, its function in BAT has not been explored. Here, using an EndoG knockout mouse model, we demonstrate that EndoG is not essential for the expression of mitochondrial genes involved in substrate oxidation or for the induction of thermogenic genes in BAT in response to cold exposure. We also show that a lack of EndoG is associated with an increased expression of thermogenic genes (ie, uncoupling protein-1, peroxisome proliferator-activated receptor-γ coactivator-1α) in white adipose tissue (WAT) that correlates with the appearance of brown adipocyte-like cells interspersed among white adipocytes. Interestingly, the increased browning of WAT elicited by the lack of EndoG was associated with a better glucose tolerance and reduced fat mass. Our results suggest that the induction of browning in WAT by means of inhibiting EndoG activity appears as a potential therapeutic strategy to prevent obesity and ameliorate glucose intolerance.
authors.affiliation: Laboratory of Metabolism and Obesity (R.P., M.V., J.A.V.) and Group of Diabetes and Metabolism (R.S.), Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Cell Signaling and Apoptosis Group (N.B., D.S.), Biomedical Research Institute of Lleida, University of Lleida, 25003 Lleida, Spain; Department of Physiology (D.B., R.N.), Center for Research in Molecular Medicine and Chronic Diseases, Universidad de Santiago de Compostela, and Centro de Investigación Biomédica en Red on Physiopathology of Obesity and Nutrition (D.B., R.N.), 15705 Santiago de Compostela, Spain; Laboratory Animal Applied Research Platform (X.C.), Scientific Park of Barcelona, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red on Diabetes and Associated Metabolic Diseases (J.A.V. R.S.), 08003 Barcelona, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pardo
authors.affiliation: Laboratory of Metabolism and Obesity (R.P., M.V., J.A.V.) and Group of Diabetes and Metabolism (R.S.), Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Cell Signaling and Apoptosis Group (N.B., D.S.), Biomedical Research Institute of Lleida, University of Lleida, 25003 Lleida, Spain; Department of Physiology (D.B., R.N.), Center for Research in Molecular Medicine and Chronic Diseases, Universidad de Santiago de Compostela, and Centro de Investigación Biomédica en Red on Physiopathology of Obesity and Nutrition (D.B., R.N.), 15705 Santiago de Compostela, Spain; Laboratory Animal Applied Research Platform (X.C.), Scientific Park of Barcelona, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red on Diabetes and Associated Metabolic Diseases (J.A.V. R.S.), 08003 Barcelona, Spain.
authors.forename: Natividad
authors.initials: N
authors.lastname: Blasco
authors.affiliation: Laboratory of Metabolism and Obesity (R.P., M.V., J.A.V.) and Group of Diabetes and Metabolism (R.S.), Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Cell Signaling and Apoptosis Group (N.B., D.S.), Biomedical Research Institute of Lleida, University of Lleida, 25003 Lleida, Spain; Department of Physiology (D.B., R.N.), Center for Research in Molecular Medicine and Chronic Diseases, Universidad de Santiago de Compostela, and Centro de Investigación Biomédica en Red on Physiopathology of Obesity and Nutrition (D.B., R.N.), 15705 Santiago de Compostela, Spain; Laboratory Animal Applied Research Platform (X.C.), Scientific Park of Barcelona, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red on Diabetes and Associated Metabolic Diseases (J.A.V. R.S.), 08003 Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vilà
authors.affiliation: Laboratory of Metabolism and Obesity (R.P., M.V., J.A.V.) and Group of Diabetes and Metabolism (R.S.), Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Cell Signaling and Apoptosis Group (N.B., D.S.), Biomedical Research Institute of Lleida, University of Lleida, 25003 Lleida, Spain; Department of Physiology (D.B., R.N.), Center for Research in Molecular Medicine and Chronic Diseases, Universidad de Santiago de Compostela, and Centro de Investigación Biomédica en Red on Physiopathology of Obesity and Nutrition (D.B., R.N.), 15705 Santiago de Compostela, Spain; Laboratory Animal Applied Research Platform (X.C.), Scientific Park of Barcelona, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red on Diabetes and Associated Metabolic Diseases (J.A.V. R.S.), 08003 Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Beiroa
authors.affiliation: Laboratory of Metabolism and Obesity (R.P., M.V., J.A.V.) and Group of Diabetes and Metabolism (R.S.), Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Cell Signaling and Apoptosis Group (N.B., D.S.), Biomedical Research Institute of Lleida, University of Lleida, 25003 Lleida, Spain; Department of Physiology (D.B., R.N.), Center for Research in Molecular Medicine and Chronic Diseases, Universidad de Santiago de Compostela, and Centro de Investigación Biomédica en Red on Physiopathology of Obesity and Nutrition (D.B., R.N.), 15705 Santiago de Compostela, Spain; Laboratory Animal Applied Research Platform (X.C.), Scientific Park of Barcelona, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red on Diabetes and Associated Metabolic Diseases (J.A.V. R.S.), 08003 Barcelona, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Nogueiras
authors.affiliation: Laboratory of Metabolism and Obesity (R.P., M.V., J.A.V.) and Group of Diabetes and Metabolism (R.S.), Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Cell Signaling and Apoptosis Group (N.B., D.S.), Biomedical Research Institute of Lleida, University of Lleida, 25003 Lleida, Spain; Department of Physiology (D.B., R.N.), Center for Research in Molecular Medicine and Chronic Diseases, Universidad de Santiago de Compostela, and Centro de Investigación Biomédica en Red on Physiopathology of Obesity and Nutrition (D.B., R.N.), 15705 Santiago de Compostela, Spain; Laboratory Animal Applied Research Platform (X.C.), Scientific Park of Barcelona, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red on Diabetes and Associated Metabolic Diseases (J.A.V. R.S.), 08003 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Cañas
authors.affiliation: Laboratory of Metabolism and Obesity (R.P., M.V., J.A.V.) and Group of Diabetes and Metabolism (R.S.), Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Cell Signaling and Apoptosis Group (N.B., D.S.), Biomedical Research Institute of Lleida, University of Lleida, 25003 Lleida, Spain; Department of Physiology (D.B., R.N.), Center for Research in Molecular Medicine and Chronic Diseases, Universidad de Santiago de Compostela, and Centro de Investigación Biomédica en Red on Physiopathology of Obesity and Nutrition (D.B., R.N.), 15705 Santiago de Compostela, Spain; Laboratory Animal Applied Research Platform (X.C.), Scientific Park of Barcelona, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red on Diabetes and Associated Metabolic Diseases (J.A.V. R.S.), 08003 Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
authors.affiliation: Laboratory of Metabolism and Obesity (R.P., M.V., J.A.V.) and Group of Diabetes and Metabolism (R.S.), Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Cell Signaling and Apoptosis Group (N.B., D.S.), Biomedical Research Institute of Lleida, University of Lleida, 25003 Lleida, Spain; Department of Physiology (D.B., R.N.), Center for Research in Molecular Medicine and Chronic Diseases, Universidad de Santiago de Compostela, and Centro de Investigación Biomédica en Red on Physiopathology of Obesity and Nutrition (D.B., R.N.), 15705 Santiago de Compostela, Spain; Laboratory Animal Applied Research Platform (X.C.), Scientific Park of Barcelona, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red on Diabetes and Associated Metabolic Diseases (J.A.V. R.S.), 08003 Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sanchis
authors.affiliation: Laboratory of Metabolism and Obesity (R.P., M.V., J.A.V.) and Group of Diabetes and Metabolism (R.S.), Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Cell Signaling and Apoptosis Group (N.B., D.S.), Biomedical Research Institute of Lleida, University of Lleida, 25003 Lleida, Spain; Department of Physiology (D.B., R.N.), Center for Research in Molecular Medicine and Chronic Diseases, Universidad de Santiago de Compostela, and Centro de Investigación Biomédica en Red on Physiopathology of Obesity and Nutrition (D.B., R.N.), 15705 Santiago de Compostela, Spain; Laboratory Animal Applied Research Platform (X.C.), Scientific Park of Barcelona, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red on Diabetes and Associated Metabolic Diseases (J.A.V. R.S.), 08003 Barcelona, Spain.
authors.forename: Josep A
authors.initials: JA
authors.lastname: Villena
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000166:cytology*; D050154:Adiposity; D000818:Animals; D003080:Cold Temperature; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance; D006706:Homeostasis; D008297:Male; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D001678:Organelle Biogenesis; D010085:Oxidative Phosphorylation; D022722:Thermogenesis
chemical_list: D004706:Endodeoxyribonucleases; C052391:endonuclease G; D005947:Glucose