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

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 uri...

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Published in:Journal of translational medicine Vol. 18; no. 1; pp. 122 - 15
Main Authors: Olsen, Thomas, Øvrebø, Bente, Haj-Yasein, Nadia, Lee, Sindre, Svendsen, Karianne, Hjorth, Marit, Bastani, Nasser E., Norheim, Frode, Drevon, Christian A., Refsum, Helga, Vinknes, Kathrine J.
Format: Journal Article
Language:English
Published: London BioMed Central 11.03.2020
BioMed Central Ltd
Springer Nature B.V
BMC
Subjects:
Adipose Tissue
Amino acids
Biological markers
Biomarkers
Biomedical and Life Sciences
Biomedicine
Body fat
Body weight
Cysteine
Cystine
Diet
Dietary intervention
Dietary restrictions
Double-blind studies
Fasting
Fibroblast Growth Factors
Gene Expression
Genes
Genetic aspects
Genetic markers
Genetic research
Health
Health aspects
Humans
Insulin
Medicine/Public Health
Messenger RNA
Methionine
Methionine restriction
mRNA expression
Nutrition & metabolism
Obesity
Obesity - genetics
Overweight
Overweight - genetics
Pilot Projects
Plasma biomarkers
RNA
Rodents
Translational research
Women
Norway
Dietary intervention
Translational research
Adipose tissue
Plasma biomarkers
Methionine restriction
mRNA expression
ISSN:1479-5876, 1479-5876
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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 .
AbstractList 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. Twenty women with overweight or obesity were allocated to a diet low (Met/Cys.sub.-low, n = 7), medium (Met/Cys.sub.-medium, n = 7) or high (Met/Cys.sub.-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. Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys.sub.-low vs. Met/Cys.sub.-high group. The Met/Cys.sub.-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.sub.-low group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys.sub.-high group. The participants reported satisfactory compliance and that the diets were moderately easy to follow. 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.
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.sub.-low, n = 7), medium (Met/Cys.sub.-medium, n = 7) or high (Met/Cys.sub.-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.sub.-low vs. Met/Cys.sub.-high group. The Met/Cys.sub.-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.sub.-low group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys.sub.-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 Keywords: Methionine restriction, Dietary intervention, Plasma biomarkers, Translational research, Adipose tissue, mRNA expression
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. Twenty women with overweight or obesity were allocated to a diet low (Met/Cys n = 7), medium (Met/Cys n = 7) or high (Met/Cys 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. Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys vs. Met/Cys group. The Met/Cys 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 group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys group. The participants reported satisfactory compliance and that the diets were moderately easy to follow. 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.
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 .
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.
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 .
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.BACKGROUNDDietary 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.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.METHODSTwenty 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.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.RESULTSPlasma 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.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.CONCLUSIONSOur 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.
ArticleNumber 122
Audience Academic
Author Norheim, Frode
Øvrebø, Bente
Vinknes, Kathrine J.
Hjorth, Marit
Haj-Yasein, Nadia
Lee, Sindre
Refsum, Helga
Olsen, Thomas
Bastani, Nasser E.
Drevon, Christian A.
Svendsen, Karianne
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  email: thomas.olsen@medisin.uio.no
  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
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  givenname: Bente
  surname: Øvrebø
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  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
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  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
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  surname: Lee
  fullname: Lee, Sindre
  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
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  givenname: Karianne
  surname: Svendsen
  fullname: Svendsen, Karianne
  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, The Lipid Clinic, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, OUS HF Aker Sykehus
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  surname: Hjorth
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  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
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  surname: Bastani
  fullname: Bastani, Nasser E.
  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
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  surname: Norheim
  fullname: Norheim, Frode
  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
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  surname: Drevon
  fullname: Drevon, Christian A.
  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
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  surname: Refsum
  fullname: Refsum, Helga
  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
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  givenname: Kathrine J.
  surname: Vinknes
  fullname: Vinknes, Kathrine J.
  organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32160926$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords Dietary intervention
Translational research
Adipose tissue
Plasma biomarkers
Methionine restriction
mRNA expression
Language English
License Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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Snippet Background Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational...
Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational potential...
Background Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational...
Abstract Background Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the...
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StartPage 122
SubjectTerms Adipose Tissue
Amino acids
Biological markers
Biomarkers
Biomedical and Life Sciences
Biomedicine
Body fat
Body weight
Cysteine
Cystine
Diet
Dietary intervention
Dietary restrictions
Double-blind studies
Fasting
Fibroblast Growth Factors
Gene Expression
Genes
Genetic aspects
Genetic markers
Genetic research
Health
Health aspects
Humans
Insulin
Medicine/Public Health
Messenger RNA
Methionine
Methionine restriction
mRNA expression
Nutrition & metabolism
Obesity
Obesity - genetics
Overweight
Overweight - genetics
Pilot Projects
Plasma biomarkers
RNA
Rodents
Translational research
Women
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Title 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
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