title: Nitric oxide and energy metabolism in mammals.
abstract: Nitric oxide (NO) is a signaling molecule synthesized from L-arginine by NO synthase in animals. Increasing evidence shows that NO regulates the mammalian metabolism of energy substrates and that these effects of NO critically depend on its concentrations at the reaction site and the period of exposure. High concentrations of NO (in the micromolar range) irreversibly inhibit complexes I, II, III, IV, and V in the mitochondrial respiratory chain, whereas physiological levels of NO (in the nanomolar range) reversibly reduce cytochomrome oxidase. Thus, NO reduces oxygen consumption by isolated mitochondria to various extents. In intact cells, through cGMP and AMP-activated protein kinase signaling, physiological levels of NO acutely stimulate uptake and oxidation of glucose and fatty acids by skeletal muscle, heart, liver, and adipose tissue, while inhibiting the synthesis of glucose, glycogen and fat in the insulin-sensitive tissues, and enhancing lipolysis in white adipocytes. Chronic effects of physiological levels of NO in vivo include stimulation of angiogenesis, blood flow, mitochondrial biogenesis, and brown adipocyte development. Modulation of NO-mediated pathways through dietary supplementation with L-arginine or its precursor L-citrulline may provide an effective, practical strategy to prevent and treat metabolic syndrome, including obesity, diabetes, and dyslipidemia in mammals, including humans.
authors.affiliation: State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China.
authors.forename: Zhaolai
authors.initials: Z
authors.lastname: Dai
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Junjun
authors.initials: J
authors.lastname: Wang
authors.forename: M Carey
authors.initials: MC
authors.lastname: Satterfield
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Meininger
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D002001:Adipose Tissue, Brown / Q000503:physiopathology; D000818:Animals; D019069:Cell Respiration; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009765:Obesity / Q000378:metabolism / Q000628:therapy; D010084:Oxidation-Reduction; D012039:Regional Blood Flow; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide
keywords: energy metabolism; mitochondria; nitric oxide; oxidation