Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study

Thomas Olsen; Bente Øvrebø; Nadia Haj-Yasein; Sindre Lee; Karianne Svendsen; Marit Hjorth; Nasser E Bastani; Frode Norheim; Christian A Drevon; Helga Refsum; Kathrine J Vinknes

doi:10.1186/s12967-020-02288-x

Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study

J Transl Med. 2020 Mar 11;18(1):122. doi: 10.1186/s12967-020-02288-x.

Authors

Affiliations

¹ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Postboks 1046, Blindern, 0317, Oslo, Norway. thomas.olsen@medisin.uio.no.
² Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Postboks 1046, Blindern, 0317, Oslo, Norway.
³ The Lipid Clinic, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, OUS HF Aker Sykehus, Postboks 4959, Nydalen, 0424, Oslo, Norway.

Abstract

Background: Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational potential in humans, we evaluated the effects of dietary methionine and cysteine restriction on cardiometabolic risk factors, plasma and urinary amino acid profile, serum fibroblast growth factor 21 (FGF21), and subcutaneous adipose tissue gene expression in women with overweight and obesity in a double-blind randomized controlled pilot study.

Methods: Twenty women with overweight or obesity were allocated to a diet low (Met/Cys_-low, n = 7), medium (Met/Cys_-medium, n = 7) or high (Met/Cys_-high, n = 6) in methionine and cysteine for 7 days. The diets differed only by methionine and cysteine content. Blood and urine were collected at day 0, 1, 3 and 7 and subcutaneous adipose tissue biopsies were taken at day 0 and 7.

Results: Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys_-low vs. Met/Cys_-high group. The Met/Cys_-low group had increased mRNA expression of lipogenic genes in adipose tissue including DGAT1. When we excluded one participant with high fasting insulin at baseline, the Met/Cys_-low group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys_-high group. The participants reported satisfactory compliance and that the diets were moderately easy to follow.

Conclusions: Our data suggest that dietary methionine and cysteine restriction may have beneficial effects on circulating biomarkers, including FGF21, and influence subcutaneous adipose tissue gene expression. These results will aid in the design and implementation of future large-scale dietary interventions with methionine and cysteine restriction. Trial registration ClinicalTrials.gov Identifier: NCT03629392, registration date: 14/08/2018 https://clinicaltrials.gov/ct2/show/NCT03629392.

Keywords: Adipose tissue; Dietary intervention; Methionine restriction; Plasma biomarkers; Translational research; mRNA expression.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue
Biomarkers
Cysteine*
Diet
Fibroblast Growth Factors
Gene Expression
Humans
Methionine*
Obesity / genetics
Overweight / genetics
Pilot Projects

Substances

Biomarkers
fibroblast growth factor 21
Fibroblast Growth Factors
Methionine
Cysteine

Associated data

ClinicalTrials.gov/NCT03629392