The Effect of Dairy Fat and Inulin on Fasting Induced Adipose Factor (FIAF) Blood Concentrations

Study Overview
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Brief Summary
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The objective of this study is to investigate whether intake of a diet with a high content of butyrate (from dairy fat) can affect blood FIAF concentration compared to a control diet. Further to examine whether high intake of inulin (a prebiotic) can increase the proportion of butyrate-producing bacteria in the gut and thereby affect blood FIAF concentration. In addition, the correlation between FIAF blood concentrations and resting energy expenditure, blood lipid profile and gut microbiota composition will be investigated. Furthermore, this study will investigate whether the source of FIAF can be determined. To this end, adipose tissue biopsies will be analyzed and an in vitro experiment with fecal water samples will be carried out. The study is a crossover randomized controlled trials with 3 arms. Each arm has a duration of 3 weeks. 20 overweight/obese subjects will be enrolled into the study and randomized to the order of interventions. Before and after each intervention period, blood samples will be collected and the participants will have their resting metabolic rate measured. At the end of each intervention period, the participants will collect feces for 5 consecutive days. In addition, adipose tissue biopsies will be taken after each intervention period.

Official Title
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The Effect of Dairy Fat and Inulin on Fasting Induced Adipose Factor (FIAF) Blood Concentrations

Conditions
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Obesity

Intervention / Treatment
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* Other: Inulin
* Other: Complete diet
* Other: Whole milk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males Age: 23-45 BMI: 25-32 kg/m2 Body fat percentage (BFP) > 25 Exclusion Criteria: Chronic diseases (known diabetes, cardiovascular disease (CVD), Intestinal Bowel Disease and other chronic diseases likely to affect the results of the present study) Milk allergy/lactose intolerance Intolerance towards inulin Fasting glucose ≥7.0 mmol/l or non-fasting glucose ≥ 11 mmol/l* Use of antibiotics 2 months before commencement of study Use of dietary supplements incl. multivitamins during run-in and the entire study period Smoking Elite athletes (>10 hours of strenuous physical activity per week) Use of prescription medicine which could affect the results of the present study, including systemic glucocorticoids Use of lipid-lowering agents or medication with contraindications for a high fat diet Blood pressure > 140/90 mmHg Blood donation <1 month before study commencement and during study period Simultaneous participation in other clinical studies Inability, physically or mentally, to comply with the procedures required by the study protocol, as evaluated by the study staff

Ages Eligible for Study
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Minimum Age: 23 Years
Maximum Age: 45 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Inulin<br>The participants will be given all dietary items in their diet. In the inulin arm, approximately 15 grams of inulin will be included in the diet. | Other: Inulin<br>* The participants will be given all dietary items in their diet. In the inulin arm, approximately 15 grams of inulin will be included in the diet.<br>Other: Complete diet<br>* The participants will be given all dietary items in their diet with no additional products.<br>|
| Active Comparator: Whole milk<br>The participants will be given all dietary items in their diet. In the whole milk arm, approximately 1 liter of whole milk will be included in the diet. | Other: Complete diet<br>* The participants will be given all dietary items in their diet with no additional products.<br>Other: Whole milk<br>* The participants will be given all dietary items in their diet. In the whole milk arm, approximately 1 liter of whole milk will be included in the diet.<br>|
| Placebo Comparator: Complete diet<br>The participants will be given all dietary items in their diet. | Other: Complete diet<br>* The participants will be given all dietary items in their diet with no additional products.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in FIAF blood concentration |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood lipid profile including triglyceride, free fatty acid, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glycerol, butyrate |  | 21 days | 
| Changes in microbiotic composition and characterization of gut microbiota, including metabolites |  | 21 days | 
| Changes in short-chain fatty acid content of feces (butyrate, propionate and acetate) |  | 21 days | 
| Changes in resting energy expenditure/lipid oxidation |  | 21 days | 
| Changes in parameters involved in glucose metabolism |  | 21 days | 
| Changes in FIAF adipose tissue messenger ribonucleic acid (mRNA) levels |  | 21 days | 
| Changes in gene expression and protein concentration of genes/proteins related to obesity, lipid metabolism, adipocyte differentiation, hypoxia and FIAF signaling in adipose tissue |  | 21 days | 
| Changes in FIAF mRNA/protein expressed in or secreted from human intestinal cell lines |  | 21 days |