title: Role of vascular oxidative stress in obesity and metabolic syndrome.
abstract: Obesity is associated with vascular diseases that are often attributed to vascular oxidative stress. We tested the hypothesis that vascular oxidative stress could induce obesity. We previously developed mice that overexpress p22phox in vascular smooth muscle, tg(sm/p22phox), which have increased vascular ROS production. At baseline, tg(sm/p22phox) mice have a modest increase in body weight. With high-fat feeding, tg(sm/p22phox) mice developed exaggerated obesity and increased fat mass. Body weight increased from 32.16 ± 2.34 g to 43.03 ± 1.44 g in tg(sm/p22phox) mice (vs. 30.81 ± 0.71 g to 37.89 ± 1.16 g in the WT mice). This was associated with development of glucose intolerance, reduced HDL cholesterol, and increased levels of leptin and MCP-1. Tg(sm/p22phox) mice displayed impaired spontaneous activity and increased mitochondrial ROS production and mitochondrial dysfunction in skeletal muscle. In mice with vascular smooth muscle-targeted deletion of p22phox (p22phox(loxp/loxp)/tg(smmhc/cre) mice), high-fat feeding did not induce weight gain or leptin resistance. These mice also had reduced T-cell infiltration of perivascular fat. In conclusion, these data indicate that vascular oxidative stress induces obesity and metabolic syndrome, accompanied by and likely due to exercise intolerance, vascular inflammation, and augmented adipogenesis. These data indicate that vascular ROS may play a causal role in the development of obesity and metabolic syndrome.
authors.affiliation: Division of Molecular Medicine and Cardiology, Cardiovascular Research Laboratories, Departments of Anesthesiology and Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Youn
authors.affiliation: Division of Molecular Medicine and Cardiology, Cardiovascular Research Laboratories, Departments of Anesthesiology and Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.
authors.forename: Kin Lung
authors.initials: KL
authors.lastname: Siu
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: Heinrich E
authors.initials: HE
authors.lastname: Lob
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: Hana
authors.initials: H
authors.lastname: Itani
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN hcai@mednet.ucla.edu david.g.harrison@vanderbilt.edu.
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
authors.affiliation: Division of Molecular Medicine and Cardiology, Cardiovascular Research Laboratories, Departments of Anesthesiology and Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA hcai@mednet.ucla.edu david.g.harrison@vanderbilt.edu.
authors.forename: Hua
authors.initials: H
authors.lastname: Cai
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004351:Drug Resistance / Q000235:genetics; D020738:Leptin / Q000494:pharmacology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism
chemical_list: D003573:Cytochrome b Group; D020738:Leptin; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C515614:Cyba protein, mouse