Stearoyl-CoA Desaturase and Energy Metabolism in Humans (SEM)

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Obesity
• Intervention / Treatment: Behavioral: PUFA-Cys/Met diet; Behavioral: SFA+Cys/Met diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • University of Oslo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Dietary intervention	Behavioral: PUFA-Cys/Met diet; 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).
Active Comparator: Group B; Dietary intervention	Behavioral: SFA+Cys/Met diet; Provision of food and supplements that are rich in saturated fatty acids (SFA) and the amino acids cysteine (Cys) and methionine (Met).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Oslo
• Collaborators: The Research Council of Norway; University of Oxford

Publications and helpful links

General Publications

• Olsen T, Ovrebo B, Turner C, Bastani NE, Refsum H, Vinknes KJ. Effects of short-term methionine and cysteine restriction and enrichment with polyunsaturated fatty acids on oral glucose tolerance, plasma amino acids, fatty acids, lactate and pyruvate: results from a pilot study. BMC Res Notes. 2021 Feb 2;14(1):43. doi: 10.1186/s13104-021-05463-5.
• Olsen T, Turner C, Ovrebo B, Bastani NE, Refsum H, Vinknes KJ. Postprandial effects of a meal low in sulfur amino acids and high in polyunsaturated fatty acids compared to a meal high in sulfur amino acids and saturated fatty acids on stearoyl CoA-desaturase indices and plasma sulfur amino acids: a pilot study. BMC Res Notes. 2020 Aug 10;13(1):379. doi: 10.1186/s13104-020-05222-y.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: December 4, 2015
• First Submitted That Met QC Criteria: January 4, 2016
• First Posted (Estimate): January 6, 2016

Study Record Updates

• Last Update Posted (Actual): September 18, 2018
• Last Update Submitted That Met QC Criteria: September 17, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Energy metabolism
• Other Study ID Numbers: 239948-A; 2015/634 (Other Identifier: South-Eastern Norway Regional Health Authority)