Role of vascular oxidative stress in obesity and metabolic syndrome.

Youn JY, Siu KL, Lob HE, Itani H, Harrison DG, Cai H
Diabetes. 2014 63 (7): 2344-55

PMID: 24550188 · PMCID: PMC4066332 · DOI:10.2337/db13-0719

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.

© 2014 by the American Diabetes Association.

MeSH Terms (17)

Adipogenesis Animals Cytochrome b Group Diet, High-Fat Drug Resistance Leptin Male Metabolic Syndrome Mice Mice, Inbred C57BL Mice, Transgenic Muscle, Smooth, Vascular NADPH Oxidases Obesity Oxidative Stress Reactive Oxygen Species Vascular Diseases

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