The brain controls weigh homeostasis via central and peripheral neural circuits. Domingos´lab has recently used optogenetics and two-photon microscopy to uncover a direct and functional connection between sympathetic neurons and adipocytes (1). Further, they found this neuro-adipose junction to drive lipolysis and fat mass reduction, and to be a peripheral effector of leptin action in the brain (1,2). As obesity is a chronic inflammatory state, the Domingos lab has started to define the molecular neuroimmune mechanisms that link inflammation to sympathetic neurons, in the context of obesity. The Domingos lab has recently discovered that the SNS neuro-adipose junction is subject to immune regulation, via specialized immune cells that possess a molecular machinery to handle sympathetic function.