Short Chain Fatty Acid Metabolism and Energy Metabolism

Study Overview
=================
Brief Summary
-----------------
Gut microbiota is being increasingly recognized as an important factor in fat distribution, insulin sensitivity and glucose and lipid metabolism. Accordingly, the intestinal microbiota could play an important role in the development of obesity and type 2 diabetes mellitus. The role of gut-derived short-chain fatty acids (SCFA), the formation of which is enhanced by microbial fermentation of fibre, is still controversial. At the present time, our understanding of the effects of SCFA on human metabolism (in gut or systemically) is still limited. The investigators hypothesize that the differential availability of SCFA impacts human metabolism differently. In this placebo controlled, double-blind, randomized crossover pilot study the investigators will validate in overweight/obese healthy male volunteers whether rectal administration of SCFA is a good model for studying the acute metabolic effects of SCFA. For this, it will be investigated if site of administration (in distal or proximal colon) of SCFA differentially affects parameters of substrate and energy metabolism and to test the duration of short-term effects of SCFA administration.

Official Title
-----------------
The Effects of Differential Short Chain Fatty Acid Availability on Human Substrate and Energy Metabolism

Conditions
-----------------
Type 2 Diabetes Mellitus, Obesity

Intervention / Treatment
-----------------
* Other: acetate or placebo infusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Overweight, obese men Exclusion Criteria: athletes diabetes mellitus

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sigmoidoscopy<br>2 actetate concentrations and 1 placebo are administered in randomized order after clipping a catheter in the proximal colon (sigmoidoscopy) | Other: acetate or placebo infusion<br> <br> |
| Experimental: colonoscopy<br>2 actetate concentrations and 1 placebo are administered in randomized order after clipping a catheter in the distal colon (colonoscopy) | Other: acetate or placebo infusion<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fat oxidation, energy expenditure | Fat oxidation and energy expenditure are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load | 1 study day for each administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hormones that influence substrate and energy metabolism | Insulin, Glucagon, GLP-1, PYY and Leptin are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load | 1 study day for each administration | 
| Inflammatory markers | LBP, TNF-α, IL-6, IL-1 are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load | 1 study day for each administration | 
| Plasma SCFA content | Plasma SCFA content (acetate, butyrate and propionate) are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load | 1 study day for each administration | 
| Circulating metabolites | Glucose, FFA, TG, Glycerol, FIAF are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load | 1 study day for each administration | 
| Appetite VAS scoring | Visual Analogue Scale for hunger and appetite are filled in during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load | 1 study day for each administration |