The brain’s hedonic valuation system’s resting-state connectivity predicts weight loss and correlates with leptin

Weight gain is often associated with the pleasure of eating foods rich in calories and lack of willpower to reduce such food cravings, but empirical evidence is sparse. Here we investigated the role that connectivity within the brain’s hedonic valuation system (BVS, the ventral striatum and the ventromedial prefrontal cortex) at rest plays (1) to predict weight gain or loss over time and (2) for homeostatic hormone regulation. We found that intrinsic connectivity within the BVS at rest (RSC) predicted out-of-sample weight changes over time in lean and obese participants. Counterintuitively, such BVS RSC was higher in lean versus obese participants before the obese participants underwent a drastic weight loss intervention (Roux-en-Y gastric bypass surgery, RYGB). The RYGB surgery increased BVS RSC in the obese after surgery. The obese participants’ increase in BVS RSC correlated with decreases in fasting state systemic leptin, a homeostatic hormone signalling satiety that has been previously linked to dopamine functioning. Taken together, our results indicate a first link between brain connectivity in reward circuits in a more tonic state at rest, homeostatic hormone regulation involved in dopamine functioning and ability to lose weight. Significance statement With obesity rates on the rise, advancing our understanding of what factors drive people’s ability to lose and gain weight is crucial. This research is the first to link what we know about the brain’s hedonic valuation system (BVS) to weight loss and homeostatic hormone regulation. We found that connectivity at rest (RSC) within the BVS system predicted changes in weight, differentiated between lean and obese participants, and increased after a weight loss intervention (gastric bypass surgery). Interestingly, the extent to which BVS RSC improved after surgery correlated to decreases in circulating levels of the satiety hormone leptin. These findings are the first to reveal the neural and hormonal determinants of weight loss, combining hedonic and homeostatic drivers of (over-)eating.