Role of Vascular Oxidative Stress in Obesity and Metabolic Syndrome

  1. Hua Cai*
  1. *Division of Molecular Medicine and Cardiology, Cardiovascular Research Laboratories (CVRL), Departments of Anesthesiology and Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA;
  2. #Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN
  1. Corresponding Authors: Hua Linda Cai, Email: hcai{at}mednet.ucla.edu, David G. Harrison, Email: david.g.harrison{at}vanderbilt.edu

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, tgsm/p22phox, which have increased vascular ROS production. At baseline, tgsm/p22phox mice have a modest increase in body weight. With high-fat feeding, tgsm/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 tgsm/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-C, and increased levels of leptin and MCP-1. Tgsm/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 (p22phoxloxp/loxp/tgsmmhc/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 implicate that vascular ROS may play a causal role in the development of obesity and metabolic syndrome.

  • Received May 4, 2013.
  • Accepted February 10, 2014.

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