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DNA methylation near CPT1A and changes in triglyceride-rich lipoproteins in response to weight-loss diet interventions

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1210/clinem/dgad086
AuthorSearch for: ; Search for: 1; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ORCID identifier: https://orcid.org/0000-0002-8041-7791
Affiliation
  1. National Research Council of Canada. Digital Technologies
FunderSearch for: National Heart, Lung, and Blood Institute; Search for: National Institute of Diabetes and Digestive and Kidney Diseases; Search for: Fogarty International Center; Search for: Tulane Research Centers of Excellence Awards; Search for: American Heart Association Predoctoral Fellowship Award
FormatText, Article
Abstract
Context: Carnitine palmitoyltransferase-1A, encoded by the CPT1A gene, plays a key role in the oxidation of long-chain fatty acids in the mitochondria and may be important in triglyceride metabolism. Previous work has shown that high fat intake was negatively associated with CPT1A methylation and positively associated with CPT1A expression. Objective: We aim to investigate the association of DNA methylation (DNAm) at the CPT1A gene with reductions in triglycerides and triglyceride-rich lipoproteins (TRLs) in response to weight-loss diet interventions. Methods: The current study included 538 White participants, who were randomly assigned to 1 of 4 diets varying in macronutrient components. We defined the regional DNAm at CPT1A as the average methylation level over CpGs within 500 bp of the 3 triglyceride-related DNAm sites. Results: Dietary fat intake significantly modified the association between baseline DNAm at CPT1A and 2-year changes in total plasma triglycerides, independent of concurrent weight loss. Among participants assigned to a low-fat diet, a higher regional DNAm level at CPT1A was associated with a greater reduction in total plasma triglycerides at 2 years (P = .01), compared with those assigned to a high-fat diet (P = .64) (P interaction = .018). Further investigation on lipids and apolipoproteins in very low-density lipoprotein (VLDL) revealed similar interaction patterns for 2-year changes in VLDL-triglycerides, VLDL-cholesterol, and VLDL-apolipoprotein B (P interaction = .009, .002, and .016, respectively), but not for VLDL-apoC-III (P interaction = .36). Conclusion: Participants with a higher regional DNAm level at CPT1A benefit more in long-term improvement in triglycerides, particularly in the TRLs and related apolipoproteins when consuming a low-fat weight-loss diet.
Publication date
PublisherOxford University Press
The Endocrine Society
In
  • The Journal of Clinical Endocrinology & Metabolism 108, no. 8 (17 February 2023): e542–e549.
LanguageEnglish
Peer reviewedYes
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Record identifier109e5c78-5b2e-4145-97ba-f478525aeeb3
Record created2023-04-24
Record modified2024-04-26
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