Dietary nitrate attenuates high-fat diet-induced obesity via mechanisms involving higher adipocyte respiration and alterations in inflammatory status.
Emerging evidence indicates that dietary nitrate can reverse several features of the metabolic syndrome, but the underlying molecular mechanisms still remain elusive. The aim of the present study was to explore mechanisms involved in the effects of dietary nitrate on the metabolic dysfunctions induced by high-fat diet (HFD) in mice. Four weeks old C57BL/6 male mice, exposed to HFD for ten weeks, were characterised by increased body weight, fat content, increased fasting glucose and impaired glucose clearance. All these metabolic abnormalities were significantly attenuated by dietary nitrate. Mechanistically, subcutaneous primary mouse adipocytes exposed to palmitate (PA) and treated with nitrite exhibited higher mitochondrial respiration, increased protein expression of total mitochondrial complexes and elevated gene expression of the thermogenesis gene UCP-1, as well as of the creatine transporter SLC6A8. Finally, dietary nitrate increased the expression of anti-inflammatory markers in visceral fat, plasma and bone marrow-derived macrophages (Arginase-1, Egr-2, IL-10), which was associated with reduction of NADPH oxidase-derived superoxide production in macrophages. In conclusion, dietary nitrate may have therapeutic utility against obesity and associated metabolic complications possibly by increasing adipocyte mitochondrial respiration and by dampening inflammation and oxidative stress.
['Peleli|M|M|', 'Ferreira|D M S|DMS|', 'Tarnawski|L|L|', 'McCann Haworth|S|S|', 'Xuechen|L|L|', 'Zhuge|Z|Z|', 'Newton|P T|PT|', 'Massart|J|J|', 'Chagin|A S|AS|', 'Olofsson|P S|PS|', 'Ruas|J L|JL|', 'Weitzberg|E|E|', 'Lundberg|J O|JO|', 'Carlström|M|M|']
D017667:Adipocytes D000818:Animals D001786:Blood Glucose D019069:Cell Respiration D059305:Diet, High-Fat D004195:Disease Models, Animal D005786:Gene Expression Regulation D008297:Male D026901:Membrane Transport Proteins D008810:Mice, Inbred C57BL D008928:Mitochondria D009566:Nitrates D009765:Obesity D019308:Palmitic Acid D011897:Random Allocation D000071256:Uncoupling Protein 1 D015854:Up-Regulation
Metabolic syndrome Thermogenesis Visceral fat Inflammation Inorganic nitrate Mitochondria