Obesity, Type 2 Diabetes Mellitus
Conditions
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.
Interventions
Sponsors
Study design
Eligibility
Inclusion criteria
* Overweight, obese men
Exclusion criteria
* athletes * diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fat oxidation, energy expenditure | 1 study day for each administration | Fat oxidation and energy expenditure are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hormones that influence substrate and energy metabolism | 1 study day for each administration | Insulin, Glucagon, GLP-1, PYY and Leptin are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load |
| Inflammatory markers | 1 study day for each administration | LBP, TNF-α, IL-6, IL-1 are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load |
| Plasma SCFA content | 1 study day for each administration | Plasma SCFA content (acetate, butyrate and propionate) are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load |
| Circulating metabolites | 1 study day for each administration | Glucose, FFA, TG, Glycerol, FIAF are measured during fasting acetate/placebo infusion and during acetate/placebo infusion after an oral glucose load |
| Appetite VAS scoring | 1 study day for each administration | 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 |
Countries
Netherlands