Countering the Effects of Chronic Inflammation in Obesity

Dhurandhar, Nikhil V

Abstract

Obesity is linked with a chronic low grade inflammation of non-infectious origin, typically marked by a preponderance of inflammatory cytokines, and a reduced presence of anti-inflammatory cytokines in adipose tissue or circulation. Inflammation in obesity is strongly linked with insulin resistance. However, approaches such as weight loss or anti-inflammatory therapy have not been adequate in countering insulin resistance linked with inflammation and obesity. Hence, a better understanding of the origins of obesity-associated inflammation is needed to design more effective approaches. Also, novel approaches that can improve insulin resistance independent of body weight or inflammation may be highly desirable. These two aspects are briefly described here. It is postulated that a preponderance of pro- and anti-inflammatory cytokines associated with body adiposity may in fact be a mechanism to maintain body fat stores within a desirable range. Excessive fat accumulation may derail this regulation, leading to a chronic state of inflammation associated with obesity and diabetes. Recognizing this underlying physiological basis for inflammation may help in understanding why anti-inflammatory therapy has not achieved significant improvement in insulin sensitivity. Finally, a novel strategy to potentially improve glycemic control is discussed. This strategy relates to a template offered by Ad36, -a human adenovirus, and its E4orf1 protein, which can enhance glucose disposal even in the presence of inflammation and obesity, and without weight loss. Overall, a different perspective about the origin of chronic inflammation, and a novel treatment strategy may help in countering the effects of chronic inflammation in obesity.