Carnitine palmitoyltransferase-1 (CPT1) functions in energy metabolism and is involved in many physiological processes including insulin-mediated inhibition of glucose production, insulin secretion, glycogen synthesis, and appetite control.
Epigenome-wide association studies have identified the cg00574958 DNA methylation site at the carnitine palmitoyltransferase-1A (CPT1A) gene to be associated with reduced risk of metabolic diseases, but the mechanism underlying these associations is unknown
In the current meta-analysis, scientists from the U.S. Department of Agriculture's (USDA) Agriculture Research Service (ARS), hypothesised that total dietary carbohydrate (CHO) and fat (FAT) intakes affect methylation of the carnitine palmitoyltransferase 1A gene (CPT1A), leading to altered gene expression and risk of metabolic diseases.
The authors determined the correlation between CHO and FAT intake and methylation at cg00574958 in the CPT1A promoter in the Genetics of Lipid Lowering Drugs and Diet Network study (GOLDN) before replicating the analysis in two additional cohorts: the Framingham Heart Study (FHS) and the REgistre GIroní del COR (REGICOR) study. They conducted a meta-analysis, and examined the correlation of CHO and FAT intake with CPT1A transcription, and then performed mediation analysis with CPT1A as the mediator.
They found that high carbohydrate intake is associated with lower levels of the CPT1A gene, while high fat intake is associated with higher levels. They explain that the "epigenetic signal" associated with this gene becomes stronger or weaker based on the foods we eat, causing the body to produce more or less of the gene.
"This is exciting for nutrition research because it gives insight on how balanced nutrition can affect our health, from the perspective of an important, but single gene called CPT1A," said ARS Scientist Dr. Chao-Qiang Lai. "I can't say that eating all carbs will prevent you from developing type 2 diabetes and I can't say that avoiding fat will protect you from obesity. A balanced intake of carbohydrate and fat may be the best way to prevent metabolic diseases."
The authors note that their analysis is based on observational studies so future intervention studies in humans are needed to confirm causal effects.
The American Journal of Clinical Nutrition
Ordovas. J., M., et al
Carbohydrate and fat intake associated with risk of metabolic diseases through epigenetics of CPT1A