DNA Methylation Near CPT1A and Changes in Triglyceride-rich Lipoproteins in Response to Weight-loss Diet Interventions.

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.

• Authors: Xiang Li, Xiaojian Shao, Qiaochu Xue, Minghao Kou, Catherine M Champagne, Boryana S Koseva, Yoriko Heianza, Elin Grundberg, Lydia A Bazzano, George A Bray, Frank M Sacks, Lu Qi
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 108 Issue 8 Pg. e542-e549 (Jul 14 2023) ISSN: 1945-7197 [Electronic] United States
• PMID: 36800272 (Publication Type: Randomized Controlled Trial, Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Apolipoproteins
• Carnitine O-Palmitoyltransferase
• Lipoproteins
• Lipoproteins, LDL
• Lipoproteins, VLDL
• Triglycerides
• CPT1A protein, human

Topics

• Humans
• Apolipoproteins (genetics, metabolism)
• Carnitine O-Palmitoyltransferase (genetics)
• Diet, Reducing
• DNA Methylation
• Lipoproteins
• Lipoproteins, LDL
• Lipoproteins, VLDL
• Triglycerides