Fatty acid-binding protein 4 (FABP4; also known as aP2) is an active adipokine that regulates hepatic glucose production and systemic glucose homeostasis and has been implicated in the pathogenesis of diabetes. However, therapeutically targeting FABP4 has so far been challenging. Now, Burak et al. identify a FABP4-specific monoclonal antibody — CA33 — that improved glucose metabolism, decreased fat mass, increased systemic insulin sensitivity and reduced liver steatosis in genetic and dietary mouse obesity models.