Diet, Insulin Sensitivity And the Brain

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Obesity, Diabetes Mellitus Type 2

Intervention / Treatment
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* Other: Meal size increase with HFHS
* Other: Meal size increase with HS
* Other: Meal frequency increase with HFHS
* Other: Meal frequency increase with HS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Meal size increase with HFHS<br>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®) | Other: Meal size increase with HFHS<br>* 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.<br>* Other names: Nutridrink;|
| Experimental: Meal size increase with HS<br>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. | Other: Meal size increase with HS<br>* 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.<br>|
| Experimental: Meal frequency increase with HFHS<br>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. | Other: Meal frequency increase with HFHS<br>* 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.<br>* Other names: Nutridrink;|
| Experimental: Meal frequency increase with HS<br>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. | Other: Meal frequency increase with HS<br>* 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.<br>|
| No Intervention: Control group<br>Subjects will not follow any diet but their own ad-libitum, healty diet. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At baseline and after 6 weeks of hypercaloric HFHS or HS diet | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abdominal fat mass | Changes in accumulated amount of abdominal (visceral) and liver fat | At baseline and after 6 weeks of HFHS or HS hypercaloric diet | 
| Glucoregularoty hormones | Changes in glucoregulatory hormones such as glucagon and leptin | 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 | At baseline and after 6 weeks of hypercaloric HFHS- or HS diet | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diet manipulation, serotonin, dopamine, insulin sensitivity