Diabetes Mellitus Type 2, Obesity
Conditions
Keywords
diet manipulation, serotonin, dopamine, insulin sensitivity
Brief summary
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.
Detailed description
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.
Interventions
OTHERMeal size increase with HFHS
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.
OTHERMeal size increase with HS
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.
OTHERMeal frequency increase with HFHS
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.
OTHERMeal frequency increase with HS
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.
Sponsors
Netherlands Organisation for Scientific Research
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral binding of [123I]FP-CIT to serotonin- and dopamine transporters and correlation with changes in in vivo and ex vivo insulin sensitivity | At baseline and after 6 weeks of hypercaloric HFHS or HS diet | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Abdominal fat mass | At baseline and after 6 weeks of HFHS or HS hypercaloric diet | Changes in accumulated amount of abdominal (visceral) and liver fat |
| Glucoregularoty hormones | At baseline and after 6 weeks of hypercaloric HFHS- or HS diet | Changes in glucoregulatory hormones such as glucagon and leptin |
| Insulin signalling pathways | At baseline and after 6 weeks of hypercaloric HFHS- or HS diet | Changes in insulin signalling pathways in peripheral fat and muscle tissue |
Countries
Netherlands
Outcome results
None listed