Stearoyl-CoA Desaturase and Energy Metabolism in Humans

Conditions

Healthy, Obesity

Keywords

Energy metabolism

Brief summary

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

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.

Elshorbagy A, Bastani NE, Lee-Ødegård S, Øvrebø B, Haj-Yasein N, Svendsen K, Turner C, Refsum H, Vinknes KJ, Olsen T.

2022-12-214 citations

10.1007/s00726-022-03229-2

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.

Olsen T, Øvrebø B, Turner C, Bastani NE, Refsum H, Vinknes KJ.

2021-02-0210 citations

10.1186/s13104-021-05463-5

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.

Olsen T, Turner C, Øvrebø B, Bastani NE, Refsum H, Vinknes KJ.

2020-08-108 citations

10.1186/s13104-020-05222-y

Interventions

BEHAVIORALPUFA-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).

BEHAVIORALSFA+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).

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to 40 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Change in metabolic biomarkers	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	Measurement of biomarkers of amino acid and fatty acid metabolism, including plasma concentration of cysteine, methionine, fatty acids, and stearoyl CoA desaturase (SCD) indices

Secondary

Measure	Time frame	Description
Change in biomarkers of triglycerides metabolism	Baseline and up to 7 days	Measurements of blood parameters including LDL-/HDL-/VLDL-/total cholesterol, and triglycerides
Change in molecular signatures	Baseline and up to 7 days	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
Hunger and satiety patterns	Baseline and up to 7 days	Evaluated by plasma levels of hormones such as leptin, ghrelin, cholecystokinin, GLP-1 and PYY
Change in biomarkers of glucose metabolism	Baseline and up to 7 days	Measurements of blood parameters including glucose and insulin, and Oral Glucose Tolerance Test
Change in inflammatory markers	Baseline and up to 7 days	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.
Feasibility and compliance of the diet intervention	Up to 7 days	Evaluated by compliance questionnaires
Tolerance of the diet intervention	Up to 7 days	Assessed by blood pressure, pulse and laboratory parameters including haematology, clinical chemistry and urine analysis
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)	—

Countries

Norway

Outcome results

None listed