Brain, nutrition and metabolism: Studies in lean, obese and insulin resistant humans

This thesis describes studies on the effects of obesity, weight loss and meal timing on the human brain and glucose metabolism. We investigated effects of meal timing during a hypocaloric diet and weight loss on brain serotonin transporters (SERT) and dopamine transporters (DAT), neuronal activity patterns and metabolism. In addition, we studied the effect of bright light conditions on glucose and lipid metabolism in lean and obese subjects with type 2 diabetes (T2D). First, we show a trend towards lower hypothalamic SERT binding in obese compared to lean controls and a reduced SERT binding in the diencephalon in obese insulin resistant compared to equally obese insulin sensitive and lean subjects. Second, we show that subjects who consumed most of the calories in the morning during a hypocaloric diet, increased striatal DAT binding and reduced neuronal activation in response to high calorie food pictures in the caudate nucleus, while consuming most of the calories in the evening reduced striatal DAT binding and increased neuronal activation in response to high calorie food pictures in the caudate nucleus. Metabolism and intrahepatic triglyceride content improved after weight loss but without a differential effect of meal timing. Finally, we found that acute exposure to bright light affects glucose metabolism in obese subjects with T2D and lipid metabolism in both, patients with T2D and healthy controls. Taken together, this thesis provides data supporting a clinically relevant interaction between meal timing, body weight loss and the brain, and between light exposure and metabolism.