Individuals with the metabolic syndrome are at risk of coronary heart disease, stroke, vascular disease, and type 2 diabetes. Although risk factors for this syndrome are known to include obesity, physical inactivity, and genetic factors, the mechanistic role of obesity is not completely understood. In the December 15 issue of the Journal of Clinical Investigation, Iichiro Shimomura and researchers from Osaka University, Japan, show that fat cells of obese mice produce increased levels of toxic oxygen molecules known as reactive oxygen species (ROS) as well as the enzyme NADPH oxidase. Furthermore, these cells express decreased levels of antioxidative enzymes that are responsible for destroying these toxic forms of oxygen. The effect of this oxidative stress causes changes in the production of fat-derived hormones known as adipocytokines.

The authors found that treatment of these mice with apocynin an antioxidant that inhibits NADPH oxidase reduced ROS production in fat cells, restored adipocytokine production to normal, improved diabetes, and reduced the levels of fat present in the blood and liver.

The results suggest that accumulated fatty tissue is a major source of ROS in obesity and acts as an early trigger of the metabolic syndrome. While it is too early to suggest that taking antioxidants may counter the development of obesity-associated metabolic syndrome, the steps leading to excess ROS generation may represent a potentially useful therapeutic target.

TITLE: Increased oxidative stress in obesity and its impact on metabolic syndrome

AUTHOR CONTACT:
Iichiro Shimomura
Department of Internal Medicine and Molecular Science, Osaka University, Osaka, Japan.
Phone: 81-6-6879-3730; Fax: 81-6-6879-3739; E-mail: ichi@imed2.med.osaka-u.ac.jp.

A PDF of this article is available at:

Contact: Brooke Grindlinger
press_releases@the-jci.org
212-342-9006
Journal of Clinical Investigation
15-Dec-2004