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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Most cited references 44

Record: found
Abstract: not found
Article: not found

Cutadapt removes adapter sequences from high-throughput sequencing reads

Marcel Martin (2011)

0 comments Cited 8264 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

DNA methylation and its basic function.

Lisa Moore, Thuc Le, Guoping Fan (2013)

In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factor(s) to DNA. During development, the pattern of DNA methylation in the genome changes as a result of a dynamic process involving both de novo DNA methylation and demethylation. As a consequence, differentiated cells develop a stable and unique DNA methylation pattern that regulates tissue-specific gene transcription. In this chapter, we will review the process of DNA methylation and demethylation in the nervous system. We will describe the DNA (de)methylation machinery and its association with other epigenetic mechanisms such as histone modifications and noncoding RNAs. Intriguingly, postmitotic neurons still express DNA methyltransferases and components involved in DNA demethylation. Moreover, neuronal activity can modulate their pattern of DNA methylation in response to physiological and environmental stimuli. The precise regulation of DNA methylation is essential for normal cognitive function. Indeed, when DNA methylation is altered as a result of developmental mutations or environmental risk factors, such as drug exposure and neural injury, mental impairment is a common side effect. The investigation into DNA methylation continues to show a rich and complex picture about epigenetic gene regulation in the central nervous system and provides possible therapeutic targets for the treatment of neuropsychiatric disorders.