Effect of High Caloric Diet on Brain Insulin Sensitivity and Inflammation

Study Overview
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Brief Summary
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Obesity if known to be associated with brain insulin resistance in humans and evidence is rapidly accumulating that brain insulin resistance influences peripheral metabolism, eating behavior and cognition. A reduced insulin response in the brain is found mainly in people with a metabolically unfavorable fat distribution - high visceral fat. Visceral fat produces inflammatory mediators and elevated inflammatory levels are closely linked to insulin resistance. Inflammation of the brain (i.e., neuroinflammation) has been proposed as a possible cause of brain insulin resistance. Interestingly, rodent models of a high calorie diet show that these inflammatory mechanisms occur rapidly in the brain, even prior to weight gain of the animals. Among other things, it has been shown in humans that a short-term increase in calories, especially carbohydrates and fats, reduces insulin sensitivity in the body and increases inflammatory parameters in the blood. Whether a high-calorie diet triggers insulin resistance or inflammation in the human brain is currently unknown. Aim of study: The aim of the study is to investigate the effects of a five-day high calorie diet in healthy young male volunteers on peripheral and brain insulin sensitivity as well as on eating behavior, mood and cognition. Brain insulin sensitivity, peripheral metabolism and different behavioral assessments will be evaluated before, 1 week and 2 weeks after high caloric diet.

Official Title
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Einfluss Von Hochkalorischer Nahrungsaufnahme Auf Die Insulinsensitivität Des Menschlichen Zentralnervensystems

Conditions
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Obesity, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Other: High caloric diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI 19-24 kg/m2 Non smoking normal glucose tolerance during 75g oral glucose tolerance test (OGTT) Exercise less than 2h per week Exclusion Criteria: Vegetarians and Vegans Food allergies Working at night Professional Athletes Not removable metal parts in or on the body manifest cardiovascular disease claustrophobia recent surgery (less than 3 months) Simultaneous participation in other studies Acute disease or infection within the last 4 weeks neurological and psychiatric disorders treatment with centrally acting drugs hemoglobin Hb <13g / dl Hypersensitivity to any of the substances used

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 29 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High caloric diet<br>Participants will eat 1500 kcal more than their usual diet for five days. | Other: High caloric diet<br>* After dietary counseling, subjects will receive high caloric snacks for five days.<br>|
| No Intervention: Control diet<br>Participants will eat regular diet. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brain insulin sensitivity | fMRI measurement will be performed before and after administration of 160 U of human insulin as nasal spray. Changes in regional activity will be quantified to assess regional brain insulin sensitivity. | Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet. | 
| Change in quantitative proton density | The inflammatory processes in the brain will be measured through the quantification of the water content by means of proton density imaging. | Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet. | 
| Change in brain metabolites | The inflammatory processes in the brain will be measured through the determination of brain metabolites by MR spectroscopy | Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in whole-body insulin sensitivity | Insulin sensitivity will be estimated from a frequent-sampling 75 g oral glucose tolerance test using the Matsuda formula. | Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control diet will start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet. | 
| Change in body fat distribution | Body composition will be addressed by whole-body MRI and liver MRS. | Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet. | 
| Behavioral assessment | Memory function, food reward behavior and mood will be assessed by questionnaires, neuropsychological testing and a snack test. | Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet. | 
| Change in insulin secretion | Insulin secretion will be estimated from a frequent-sampling 75 g oral glucose tolerance test. | Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet. |