Targeting Adipose Tissue Inflammation to Treat the Underlying Basis of the Metabolic Complications of Obesity

摘要

The prevalence of obesity has increased throughout the last three decades due to genetic, metabolic, behavioral, and environmental factors []. Obesity in turn increases risk for a number of metabolic diseases including type 2 diabetes, cardiovascular disease, fatty liver disease and some forms of cancer []. Despite the well-known link between obesity and increased morbidity, the mechanism of this remains elusive. Thus, the question ‘why does increased body fat cause increased metabolic comorbidities’ remains unanswered. By understanding the underlying basis of obesity-associated metabolic diseases, different therapies could be designed to target relevant pathways. Although we lack a full understanding of the underlying mechanisms that result in disease, several putative explanations exist for why fat affects metabolic health. One such theory is based on the anatomic location of fat deposition and ectopic fat accumulation []. Specifically, current literature suggests that visceral, liver and skeletal fat accumulation affects organ function and contributes to the development of insulin resistance, fatty liver, and the metabolic syndrome []. However, even in individuals matched for body fat and fat distribution, significant differences can exist in metabolic outcomes, and the phenomenon of metabolically healthy obese has been well described []. More recent data suggest the alternative hypothesis relating excess adipose tissue to disease risk based on the metabolic function and morphological properties of adipose tissue. In this scenario, excess adipose tissue is hypothesized to contribute to a state of chronic inflammation which promotes development of insulin resistance as well as other metabolic complications by stimulating nuclear factor-κB and Jun N-terminal kinase pathways in adipocytes and the liver []. In this paper, we will review the hypothesis linking excess adipose tissue to increased disease risk through adipose tissue inflammation.