Adipose tissue expansion in the face of caloric excess initiates processes including angiogenesis, inflammation, and extracellular matrix (ECM) remodeling. The small leucine-rich proteoglycan Lumican, a component of the ECM, binds collagen and is associated with repair processes in collagen-rich connective tissues. Wolff et al. explored the impact of Lumican loss and over-expression on metabolism and adipose tissue. They observed a sex-specific effect on fat accumulation in female Lumican knockout mice that coincided with increased inflammation and insulin resistance. Likewise, Lumican overexpression in the visceral fat and liver improved glucose clearance and insulin sensitivity.