Inflammation and metabolic disorders - Harvard University.pdfVIP

INSIGHT REVIEW NATURE|Vol 444 |14 December 2006 |doi:10.1038/nature05485 Inflammation and metabolic disorders Gökhan S. Hotamisligil1 Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily conserved throughout species. As a result, immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease. Collectively, these diseases constitute the greatest current threat to global human health and welfare. The incidence of obesity worldwide has increased drastically during response is a crucial component of tissue repair and involves integration recent decades. Consequently, obesity and associated disorders now of many complex signals in distinct cells and organs. However, the long- constitute a serious threat to the current and future health of all popu- term consequences of prolonged inflammation are often not beneficial. lations on Earth. The World Health Organization estimates that more This certainly seems to be the case in metabolic diseases. Although many than 1 billion adults worldwide are overweight, 300 million of whom of the same mediators are involved in obesity and diabetes, few, if any, are clinically obese — defined as having a body mass index equal to of the classic features of inflammation have been observed. Therefore, it or greater than 30 kg m–2 (ref. 1). Particularly alarming is the equally would be useful to set out a distinct fo