Central serotonin and dopamine transporters in overeating, obesity and insulin resistance

The objectives of this thesis were to study cerebral serotonin transporters (SERT) in the diencephalon and striatal dopamine transporters (DAT) in humans in different metabolic conditions (i.e. lean, obese and insulin resistant state) in relation to feeding behavior and to investigate the early consequences of overeating on diencephalic SERT and striatal DAT, on a number of metabolic parameters including fat accumulation and insulin sensitivity, and on the autonomic nervous system in lean humans. To do this, we performed a hypercaloric diet study with 4 hypercaloric diets with different meal pattern and diet composition. We measured several metabolic parameters, serotonin and dopamine transporters (SERT and DAT) in the brain, behavioral outcomes and central nervous system activity. In addition, we measured metabolic outcomes and brain SERT and DAT in obese humans with or without insulin resistance and matched lean controls. In this thesis we show that SERT and DAT in the human brain are involved in food motivated behavior and that SERT is reduced in the hypothalamus of overweight/ obese subjects and particularly in obese women with insulin resistance. Moreover we provide evidence that consuming high-fat-high-sugar snacks in excess of caloric need reduces SERT in the diencephalon and reduces hepatic insulin sensitivity in addition to the negative effects of snacking on liver and abdominal fat accumulation. Increasing meal size only did not show these effects pointing to an independent effect of hypercaloric snacking behavior on peripheral glucose metabolism and on brain circuitries involved in feeding behavior and central control of glucose metabolism.