Epidemic Inflammation: Pondering Obesity

Over the past two decades, inflammation has been recognized as a major driver in the pathogenesis of several common diseases, including atherosclerosis, diabetes, cancer, and asthma. Over the same period, there has been a steep rise in the incidence of obesity, a major risk factor for these disorders. Inflammation of adipose tissue is now recognized to accompany obesity and contribute to its sequelae. Thus, whereas obesity is primarily a disorder of energy balance, it may be helpful to consider it also as a form of epidemic inflammation that predisposes to other forms of epidemic inflammation. It is a fundamental biologic challenge to understand how a positive energy balance and inflammation are linked. This work reviews evidence that reactive oxygen and nitrogen intermediates (ROI and RNI) help drive chronic inflammation in the obese. This is proposed to be a maladaptive instance of our evolved dependence on ROI and RNI for both homeostatic signaling and host defense. ROI and RNI are well suited for these seemingly contradictory dual functions by their metabolic origin, high diffusibility in water and lipid, atomic specificity, and large number of molecular targets. When we eat so much and work so little that we repeatedly generate reactive compounds at levels normally reserved for emergencies, we treat our own cells like invading microbes.