Diet, Insulin Sensitivity And the Brain (DISAB)

The Effect of Dietary Patterns and Diet Composition on Insulin Sensitivity and Cerebral Dopamine- and Serotonin Transporters

Obesity and insulin resistance may be in part explained by an altered reward system with changes in the serotonin/dopamine system. These changes might be caused by changes in dietary habits, especially by an increased intake of liquid sugar and an increase in meal frequency. The investigators hypothesize that increasing meal frequency compared to increasing meal size and when consuming a hypercaloric high-sugar diet (HS) compared to a hypercaloric high-fat-high-sugar diet (HFHS) will result in a reduction in cerebral serotonin and dopamine transporters and in a more prominent increase in insulin resistance. In addition, the investigators hypothesize that the changes in insulin sensitivity will be independent of changes in abdominal (visceral) and liver fat and that changes in insulin sensitivity due to the dietary manipulation will co-occur with changes in insulin signaling pathways in peripheral fat and muscle tissue.

Lean, healthy, young men will follow a hypercaloric HF- or HFHS diet for 6 weeks. Before and after the dietary intervention, the investigators will perform a SPECT-scan for serotonin and dopamine transporters with the radioligand [123I]FP-CIT, administered intravenously. The investigators will also perform a structural MRI for localization. Furthermore the investigators will perform a liver MRS and abdominal MRI for liver fat- and abdominal visceral fat measurement. The investigators will also perform a euglycemic, hyperinsulinemic clamp to measure insulin sensitivity and muscle- and fat biopsies to examine changes in insulin signaling pathways and fat metabolism. After the hypercaloric diet subjects will follow a hypocaloric diet until their weight is back to baseline.

On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a liquid meal which is high in fat and sugar (Nutridrink®)

On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume this caloric surplus with their meals, which results in an increase in meal size.

On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a liquid meal which has a high fat and sugar content(Nutridrink®). Subjects consume the Nutridrink 3 times a day in between meals. which results in an increase in meal frequency.

On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages 3 times a day in between meals, which results in an increase in meal frequency.

On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a high-fat, high-sugar liquid medical food supplement (Nutridrink®). Subjects consume the Nutridrink® with their meals, which results in an increase in meal size.

On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages with their meals, which results in an increase in meal size.

On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a high-fat, high-sugar liquid medical food supplement (Nutridrink®). Subjects consume the Nutridrink® 3 times a day in between meals, which results in an increase in meal frequency.

On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages 3 times a day in between meals, which results in an increase in meal frequency.

Cerebral binding of [123I]FP-CIT to serotonin- and dopamine transporters and correlation with changes in in vivo and ex vivo insulin sensitivity

Difference in cerebral binding of the radioligand [123I]FP-CIT to serotonin- and dopamine transporters before and after dietary manipulations and correlation of cerebral dopamine and serotonin transporter binding with changes in in vivo and ex vivo insulin sensitivity.

Inclusion Criteria: BMI 19-26 kg/m2 Age 18-40 years old Male gender Caucasian Stable weight 3 months prior to start study participation Exclusion Criteria: Abnormal oral glucose tolerance test (OGTT) Lipid disorders, renal disorders, thyroid disorders, elevated liver enzymes Use of medication Use of alcohol > 3/day Use of ecstasy, amphetamines or cocaine Smoking History of eating disorder or psychiatric disorder Any medical condition, intensive sports ( >3 times/week), shift work

Koopman KE, Caan MW, Nederveen AJ, Pels A, Ackermans MT, Fliers E, la Fleur SE, Serlie MJ. Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides: a randomized controlled trial. Hepatology. 2014 Aug;60(2):545-53. doi: 10.1002/hep.27149. Epub 2014 May 13.