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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
39
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.
Academic Medical Center
Amsterdam, North Holland, Netherlands
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.
Time frame: At baseline and after 6 weeks of hypercaloric HFHS or HS diet
Abdominal fat mass
Changes in accumulated amount of abdominal (visceral) and liver fat
Time frame: At baseline and after 6 weeks of HFHS or HS hypercaloric diet
Glucoregularoty hormones
Changes in glucoregulatory hormones such as glucagon and leptin
Time frame: At baseline and after 6 weeks of hypercaloric HFHS- or HS diet
Insulin signalling pathways
Changes in insulin signalling pathways in peripheral fat and muscle tissue
Time frame: At baseline and after 6 weeks of hypercaloric HFHS- or HS diet
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