Context: STAMP2 is a counter-regulator of adipose inflammation and insulin resistance in mice. Our hypothesis was that STAMP2 could be involved in human obesity and insulin resistance.

Objective: Elucidate the role of adipose STAMP2 expression in human obesity and insulin resistance.

Design: Quantify STAMP2 in human abdominal subcutaneous and omental white adipose tissue (WAT), isolated adipocytes and stroma, and in vitro differentiated preadipocytes. Relate levels of STAMP2 in subcutaneous WAT to clinical and adipocyte phenotypes involved in insulin resistance.

Participants: Non-obese and obese women and men (N=236) recruited from an obesity clinic or through local advertisement.

Main outcome measurement: Clinical measures included body mass index, body fat, total adiponectin and homeostasis model assessment (HOMA) as measure of overall insulin resistance. In adipocytes we determined cell size, sensitivity of lipolysis and lipogenesis to insulin, adiponectin secretion, and inflammatory gene expression.

Results: STAMP2 levels in subcutaneous and visceral WAT and in adipocytes were increased in obesity (P-value 0.0008–0.05), but not influenced by weight-loss. Increased WAT STAMP2 levels associated with a high amount of body fat (P-value 0.04), high HOMA (P-value 0.01), and large adipocytes (P-value 0.02). Subjects with high STAMP2 levels displayed reduced sensitivity of adipocyte lipogenesis (P-value 0.04) and lipolysis (P-value 0.03) to insulin, but had normal adiponectin levels. WAT STAMP2 levels correlated with expression of the macrophage marker CD68 (P-value 0.0006).

Conclusion: Human WAT STAMP2 associates with obesity and insulin resistance independently of adiponectin, but the role of STAMP2 in obesity and its complications seems different than in mice.