Metabolism Select

The role of adipose tissue, or fat, in the development and treatment of metabolic disease is the subject of this issue's Select. A cluster of new studies in mice suggest that dysregulation of lymphocytes and other inflammatory cells in adipose tissue contributes to obesity and metabolic diseases such as type 2 diabetes. Elucidation of how the inflamma-tory response affects different types of adipose tissue may shed light on new strategies for treating diseases associated with obesity. The increase in metabolic diseases worldwide has been linked to a spike in obesity. Chronic inflammation of adipose tissue is known to be associated with obesity and to contribute to insulin resistance, a major feature of metabolic diseases, but how this process begins is unclear. Given the role of CD4 + regulatory T cells (Tregs) in controlling inappropriate immune responses, Feuerer et al. (2009) examine the part played by these cells in the inflammatory response in adipose tissue from lean mice. They find that Tregs are enriched in visceral adipose tissue (VAT), but not in subcutaneous adipose tissue (SAT) or other tissues. They also analyze obese mice and observe a strong correlation between insulin resistance and a lower proportion of Tregs in VAT but not other tissues. Systemic depletion of Tregs in mice induces the expression of genes encoding proinflammatory cytokines mainly in VAT, and triggers insulin resistance. On the other hand, expansion of Tregs in vivo leads to lower blood glucose concentrations and reduced glucose intolerance in mice fed a high-fat diet. Thus Tregs appear to protect against excessive inflammation of VAT and may block progression to metabolic disease. Tregs produce the cytokine interleukin-10, which inhibits the expression of proinflammatory mediators from adipocytes. Hence, this Treg-derived cytokine may directly regulate adipocyte function in VAT. In a related study, Winer et al. (2009) assess the broader CD4 + T lymphocyte population in VAT. The authors examine T cell populations from both SAT and VAT of obese and lean mice and observe increased numbers of CD4 + T cells after diet-induced obesity. Within the CD4 + T cell population, the authors find a rising bias toward proinflammatory T helper 1 (Th1) cells relative to Tregs in VAT from obese humans and mice, which appears to be antigen-driven. They find that mutant mice lacking lymphocytes and fed a high-fat diet are more prone to weight gain and developing insulin resistance than wild-type mice, suggesting that T …