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Cited by 178Lipid metabolism and biosynthesisDiet, Metabolism, and DiseaseDietary Effects on Health

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Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase

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Elshorbagy, Amany K., Valdivia-Garcia, Maria, Mattocks, Dwight A.L., Plummer, Jason D., Smith, A. David, Drevon, Christian A., Refsum, Helga, Perrone, Carmen E.·2011·Journal of Lipid Research
DOI 10.1194/jlr.m010215PMC PMC2999932
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Abstract

Stearoyl-CoA desaturase-1 (SCD1) is a key enzyme in fatty acid and energy metabolism, but little is known about its nutritional regulation. Dietary methionine restriction in rats decreases hepatic Scd1 mRNA and protein, increases energy expenditure, and decreases fat-pad mass/body-weight% (FM/BW%). In humans, plasma concentrations of the methionine product, cysteine, are associated with obesity. To determine which consequences of methionine-restriction are mediated by decreased cysteine availability, we monitored obesity-related variables in 4 dietary groups for 12 weeks: control-fed (CF), methionine-restricted (MR), MR supplemented with 0.5% l-cysteine (MR+Cys) and CF+Cys rats. MR lowered weight gain and FM/BW% despite higher food intake/weight than CF, and lowered serum cysteine. Hepatic Scd1 expression was decreased, with decreased serum SCD1 activity indices (calculated from serum fatty acid profile), decreased serum insulin, leptin and triglycerides, and higher adiponectin. Cysteine supplementation (MR+Cys) essentially reversed all these phenotypes and raised serum cysteine but not methionine to CF levels. Adding extra cysteine to control diet (CF+Cys) increased serum taurine but did not affect serum cysteine, lipids, proteins, or total weight gain. FM/BW% and serum leptin were modestly decreased. Our results indicate that anti-obesity effects of MR are caused by low cysteine and that dietary sulfur amino acid composition contributes to SCD1 regulation.

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Fig. 1. Weight gain, food intake, and weight of adipose tissues and liver in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats. Data represents mean ± SEM; N = 8 per group. A: Weight gain after 12 weeks as a percent of initial body weight. B: Food intake/ 24 h normalized to body weight. C: Fat pad and liver weights as a percent of body weight after 12 weeks. All parameters show significant differences by ANOVA (P < 0.05). Pairwise comparisons are presented only for CF versus each of the other groups, and for MR versus MR+Cys. *P < 0.05 compared with CF; **P ≤ 0.001 compared with CF; #MR+Cys significantly different from MR, P < 0.05; ##MR+Cys significantly different from MR, P ≤ 0.001. For pairwise comparisons in food intake, see text.
Fig. 1. Weight gain, food intake, and weight of adipose tissues and liver in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats. Data represents mean ± SEM; N = 8 per group. A: Weight gain after 12 weeks as a percent of initial body weight. B: Food intake/ 24 h normalized to body weight. C: Fat pad and liver weights as a percent of body weight after 12 weeks. All parameters show significant differences by ANOVA (P < 0.05). Pairwise comparisons are presented only for CF versus each of the other groups, and for MR versus MR+Cys. *P < 0.05 compared with CF; **P ≤ 0.001 compared with CF; #MR+Cys significantly different from MR, P < 0.05; ##MR+Cys significantly different from MR, P ≤ 0.001. For pairwise comparisons in food intake, see text.CC BY-NC · PubMed Central
Fig. 2. Estimated indices of desaturase and elongase activities in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats after 12 weeks. Data represents mean for six rats per group. All indices show significant differences by ANOVA (P < 0.05). *P < 0.05 compared with CF; **P ≤ 0.001 compared with CF; #MR+Cys significantly different from MR, P < 0.05; ##MR+Cys significantly different from MR, P ≤ 0.001.
Fig. 2. Estimated indices of desaturase and elongase activities in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats after 12 weeks. Data represents mean for six rats per group. All indices show significant differences by ANOVA (P < 0.05). *P < 0.05 compared with CF; **P ≤ 0.001 compared with CF; #MR+Cys significantly different from MR, P < 0.05; ##MR+Cys significantly different from MR, P ≤ 0.001.CC BY-NC · PubMed Central
Fig. 3. Changes in serum hormones and adipokines over 12 weeks in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats. Data represents mean ± SEM; N = 8 per group. All adipokines studied showed significant differences by ANOVA (P < 0.05). For relevant pair-wise comparisons, see text. One outlier value was excluded from the CF+Cys 6-week insulin data.
Fig. 3. Changes in serum hormones and adipokines over 12 weeks in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats. Data represents mean ± SEM; N = 8 per group. All adipokines studied showed significant differences by ANOVA (P < 0.05). For relevant pair-wise comparisons, see text. One outlier value was excluded from the CF+Cys 6-week insulin data.CC BY-NC · PubMed Central
Fig. 4. Changes in serum sulfur amino acids and glutamate over 12 weeks in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats. Data represents mean ± SEM; N = 8 per group. All amino acids illustrated show significant group differences by ANOVA (P < 0.05). For pair-wise comparisons, see text.
Fig. 4. Changes in serum sulfur amino acids and glutamate over 12 weeks in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats. Data represents mean ± SEM; N = 8 per group. All amino acids illustrated show significant group differences by ANOVA (P < 0.05). For pair-wise comparisons, see text.CC BY-NC · PubMed Central
Fig. 5. Gene expression profile in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats after 12 weeks of dietary intervention, in liver, inguinal white adipose tissue and quadriceps muscle. Data represents mean ± SEM; N = 8 per group. *P < 0.05 compared with CF; **P ≤ 0.001 compared with CF; #MR+Cys significantly different from MR, P < 0.05; ##MR+Cys significantly different from MR, P ≤ 0.001.
Fig. 5. Gene expression profile in CF (control-fed), CF+Cys (control-fed supplemented with cysteine), MR (methionine-restricted), and MR+Cys rats after 12 weeks of dietary intervention, in liver, inguinal white adipose tissue and quadriceps muscle. Data represents mean ± SEM; N = 8 per group. *P < 0.05 compared with CF; **P ≤ 0.001 compared with CF; #MR+Cys significantly different from MR, P < 0.05; ##MR+Cys significantly different from MR, P ≤ 0.001.CC BY-NC · PubMed Central

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Authors
Elshorbagy, A. K., Valdivia-Garcia, M., Mattocks, D. A. L., Plummer, J. D., Smith, A. D., Drevon, C. A., Refsum, H., & Perrone, C. E.
Affiliations
  • University of Oxford (GB)
  • Orentreich Foundation for the Advancement of Science (US)
  • University of Oslo (NO)
Corresponding author
Elshorbagy, Amany K.
ORCID
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2011-01
Volume
52
Issue
1
Pages
104-112
ISSN
0022-2275 (ISSN-L)
DOI
10.1194/jlr.m010215
PMC
PMC2999932
OpenAlex
W1985118273
Cited by
177
References
57
Citations by year
2026: 4 · 2025: 10 · 2024: 9 · 2023: 6 · 2022: 17 · 2021: 21 · 2020: 24 · 2019: 7 · 2018: 11 · 2017: 4 · 2016: 12 · 2015: 10 · 2014: 12 · 2013: 11 · 2012: 11
FWCI
4.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Norges Forskningsråd
  • Direktør Throne Holsts Fond For Ernæringsforskning
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
Keywords
cysteine supplementation, methionine restriction, stearoyl-CoA desaturase 1, adiposity, obesity, fat mass, sulfur-containing amino acids, energy expenditure, leptin, adiponectin, taurine, dietary fat
MeSH terms
Animals, Body Weight, Cysteine, Male, Methionine, Rats, Inbred F344, Stearoyl-CoA Desaturase, Taurine, Adiposity, Rats, Adipokines

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