Stearoyl-CoA Desaturase and Energy Metabolism in Humans

Study Overview
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Brief Summary
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The aim of this study is to examine if changing stearoyl-coenzyme A desaturase-1 (SCD1) activity through dietary interventions can increase energy metabolism in humans.

Detailed Description
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In rodents as well as humans, high stearoyl-coenzyme A desaturase-1 (SCD1) activity is considered to be involved in development of obesity. In animal models, polyunsaturated fatty acids (PUFA) inhibit Scd1 gene expression and at the population level, dietary PUFA and plasma PUFA show strong inverse associations with plasma SCD indices. Emerging evidence also suggests a role for the sulphur amino acid cysteine in regulating SCD1 activity and obesity. The overall aim of the project is to examine if interventions that lowers SCD1 activity lead to increased energy metabolism. In this project, the investigators will conduct dietary intervention trials to evaluate the effects of short-term consumption of a diet rich in polyunsaturated fatty acids (PUFA) and low in cysteine and its precursor methionine (PUFA-Cys/Met) vs. a diet rich in saturated fatty acids (SFA) and cysteine/methionine (SFA+Cys/Met) on SCD1 activity, lipids, amino acids, glucose and other biomarkers related to energy metabolism, in healthy normal-weight subjects. Healthy volunteers will be randomized to the PUFA-Cys/Met or SFA+Cys/Met diets receiving supplements/meals in a single dose or for 7 days. This study is a pilot study, with main focus on feasibility, tolerance and side effects. If the pilot shows positive results in terms of side effects, safety and tolerance, the investigators will follow-up by including obese subjects in a longer dietary intervention.

Official Title
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Stearoyl-CoA Desaturase and Energy Metabolism in Humans

Conditions
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Healthy, Obesity

Intervention / Treatment
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* Behavioral: PUFA-Cys/Met diet
* Behavioral: SFA+Cys/Met diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy normal-weight (BMI 20-25 kg/m2) Exclusion Criteria High physical activity Smoking High intake of fatty fish or cod liver oil Drugs Pregnancy or breastfeeding Chronic disease

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

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: Group A<br>Dietary intervention | Behavioral: PUFA-Cys/Met diet<br>* Provision of food and supplements that are rich in polyunsaturated fatty acids (PUFA, n-3 and n-6) and low in the amino acids cysteine (Cys) and methionine (Met).<br>|
| Active Comparator: Group B<br>Dietary intervention | Behavioral: SFA+Cys/Met diet<br>* Provision of food and supplements that are rich in saturated fatty acids (SFA) and the amino acids cysteine (Cys) and methionine (Met).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in metabolic biomarkers | Measurement of biomarkers of amino acid and fatty acid metabolism, including plasma concentration of cysteine, methionine, fatty acids, and stearoyl CoA desaturase (SCD) indices | 0 hour and at 30 min, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after single meal. Baseline and up to 7 days in 7 days intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in biomarkers of glucose metabolism | Measurements of blood parameters including glucose and insulin, and Oral Glucose Tolerance Test | Baseline and up to 7 days | 
| Change in biomarkers of triglycerides metabolism | Measurements of blood parameters including LDL-/HDL-/VLDL-/total cholesterol, and triglycerides | Baseline and up to 7 days | 
| Change in molecular signatures | Evaluation of markers related to lipid, amino acid and glucose metabolism, including measurements of mRNA expression in blood cells, and proteins and metabolites, in blood and/or urine | Baseline and up to 7 days | 
| Hunger and satiety patterns | Evaluated by plasma levels of hormones such as leptin, ghrelin, cholecystokinin, GLP-1 and PYY | Baseline and up to 7 days | 
| Appetite assessed by visual analogue scales |  | 0, 15, 30, 45, 60, 90, 120, 180 minutes postprandially (single meal intervention). Change from baseline up to 7 days (7 days intervention) | 
| Change in inflammatory markers | Measurements of blood parameters, e.g., CRP, cytokines and chemokines, adipokines, metabolic markers, hormones, growth factors, tissue remodeling proteins, angiogenesis markers, acute phase reactants, and other important circulating proteins. | Baseline and up to 7 days | 
| Feasibility and compliance of the diet intervention | Evaluated by compliance questionnaires | Up to 7 days | 
| Tolerance of the diet intervention | Assessed by blood pressure, pulse and laboratory parameters including haematology, clinical chemistry and urine analysis | Up to 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Energy metabolism