Although the adipocyte's main function is to store fat, it is becoming clearer that it also contributes to sterile inflammation. A new study by Willa A. Hsueh and her colleagues (Cell Metab. 17, 411–422) adds further insight into this role. The authors found that, compared with adipocytes from lean humans, adipocytes from obese individuals had higher expression of many genes involved in antigen presentation, including the class II major histocompatibility complex (MHCII). Similar findings were found in mice after 2 weeks of a high-fat diet. The team also uncovered a signaling pathway in mice by which adipocyte-derived leptin acts on adipose tissue–resident T cells to promote interferon-γ release. This cytokine then acts back on the adipocytes, and other antigen-presenting cells in the organ, to upregulate MHCII expression, resulting in T cell activation. This, in turn, promotes macrophage recruitment and polarization to a proinflammatory profile.

The team validated the pathological role of this signaling pathway by showing that mice deficient in either leptin or MHCII have less adipose tissue inflammation upon high-fat feeding, and in the case of the latter strain they also saw improved insulin sensitivity. One drawback to this study is that they used a strain with whole-body knockout of MHCII, so it is unclear if expression of this complex in adipocytes and/or in resident adipose tissue macrophages is necessary to cause metabolic dysfunction. Even so, the results are intriguing, especially given data from other labs showing alterations in the adipose tissue T cell receptor repertoire in obesity, suggesting that this condition is associated with antigen presentation and altered immune cell function.