title: Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms.
abstract: Insulin resistance and obesity are associated with a reduction of mitochondrial content in various tissues of mammals. Moreover, a reduced nitric oxide (NO) bioavailability impairs several cellular functions, including mitochondrial biogenesis and insulin-stimulated glucose uptake, two important mechanisms of body adaptation in response to physical exercise. Although these mechanisms have been thoroughly investigated in skeletal muscle and heart, few studies have focused on the effects of exercise on mitochondria and glucose metabolism in adipose tissue. In this study, we compared the in vivo effects of chronic exercise in subcutaneous adipose tissue of wild-type (WT) and endothelial NO synthase (eNOS) knockout (eNOS(-/-)) mice after a swim training period. We then investigated the in vitro effects of NO on mouse 3T3-L1 and human subcutaneous adipose tissue-derived adipocytes after a chronic treatment with an NO donor: diethylenetriamine-NO (DETA-NO). We observed that swim training increases mitochondrial biogenesis, mitochondrial DNA content, and glucose uptake in subcutaneous adipose tissue of WT but not eNOS(-/-) mice. Furthermore, we observed that DETA-NO promotes mitochondrial biogenesis and elongation, glucose uptake, and GLUT4 translocation in cultured murine and human adipocytes. These results point to the crucial role of the eNOS-derived NO in the metabolic adaptation of subcutaneous adipose tissue to exercise training.
authors.affiliation: Internal Medicine 3, Endocrine-Metabolic Laboratory, Department of Medicine DIMED, University of Padua, Padua, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Trevellin
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Scorzeto
authors.affiliation: Internal Medicine 3, Endocrine-Metabolic Laboratory, Department of Medicine DIMED, University of Padua, Padua, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Olivieri
authors.affiliation: Internal Medicine 3, Endocrine-Metabolic Laboratory, Department of Medicine DIMED, University of Padua, Padua, Italy.
authors.forename: Marnie
authors.initials: M
authors.lastname: Granzotto
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Valerio
authors.affiliation: Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tedesco
authors.affiliation: Internal Medicine 3, Endocrine-Metabolic Laboratory, Department of Medicine DIMED, University of Padua, Padua, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fabris
authors.affiliation: Internal Medicine 3, Endocrine-Metabolic Laboratory, Department of Medicine DIMED, University of Padua, Padua, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Serra
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Quarta
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Reggiani
authors.affiliation: Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Nisoli
authors.affiliation: Internal Medicine 3, Endocrine-Metabolic Laboratory, Department of Medicine DIMED, University of Padua, Padua, Italy roberto.vettor@unipd.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D009638:Norepinephrine; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013550:Swimming
chemical_list: D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D005947:Glucose; D009638:Norepinephrine