Key result
A low-fat weight-loss diet in participants with higher baseline DNA methylation at CPT1A was associated with a greater reduction in total plasma triglycerides at 2 years.
Why the study?
CPT1A may be important in triglyceride metabolism, and high fat intake is linked to CPT1A methylation, but its role in triglyceride reductions during weight-loss diets was unknown.
Does baseline DNA methylation at CPT1A modify the effect of a low-fat versus high-fat weight-loss diet on 2-year changes in triglycerides in White participants?
RCT (n=538)
randomly assigned
Does baseline DNA methylation at CPT1A modify the effect of a low-fat versus high-fat weight-loss diet on 2-year changes in triglycerides in White participants?
Higher baseline DNA methylation at CPT1A predicts greater long-term reductions in triglycerides and triglyceride-rich lipoproteins in response to a low-fat weight-loss diet.
Answers are grounded in this paper and cite their sources.
CPT1A methylation may guide low-fat diet selection to optimize triglyceride reductions; extends precision nutrition evidence from RCTs.
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.
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Li et al. (2023) conducted an RCT in Weight loss (n=538). Low-fat weight-loss diet vs. High-fat weight-loss diet was evaluated on 2-year changes in total plasma triglycerides (p=0.018). A low-fat weight-loss diet in participants with higher baseline DNA methylation at CPT1A was associated with a greater reduction in total plasma triglycerides at 2 years.
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