From: Fatty acids, epigenetic mechanisms and chronic diseases: a systematic review
FA | Dose | Study model | Epigenetic mechanism | Epigenetic signature | Metabolic outcomes | Reference | |
---|---|---|---|---|---|---|---|
HUMANS | |||||||
Trans FA | |||||||
Industrial TFA | 10.2 g/2500 kcal, 3.7% of daily energy | 9 healthy men | miRNAs | 5 miRNAs in purified HDLs 13 HDL-carried miRNAs to the plasmatic miRNA pool | ↑ ↑ | Related to carcinogenesis, FA biosynthesis and alteration in FA metabolism | [28] |
ANIMAL MODELS | |||||||
Transgenerational | |||||||
Elaidic acid | 20 pregnancy mice and THP-1 cells | DNA methylation | 1–50 μM 5.2% increase in 5mC up to 200 μM | + - | Favors the accumulation of adipose tissue, obesity, and hepatic steatosis | [27] | |
IN VITRO MODELS | |||||||
SFA | |||||||
Palmitic acid | 750 μM palmitate | In vitro urinary human podocyte cell line and male Sprague-Dawley rats | Histone methylation and acetylation | H3K27me3 and H3K36me2 on promoter region of FOXO1 | ↓ | Related to insulin resistance and decrease of glucose tolerance, favors gluconeogenesis. | [29] |
Palmitic acid | 1 mM palmitate | In vitro human pancreatic islets | DNA methylation | 4561 sites increased DNA methylation (2753 unique genes and 1429 intergenic sites) 129 sites decreased DNA methylation (99 unique genes, and 30 intergenic sites. | + - | Associated with insulin resistance, lipotoxicity, T2D, glycolysis, gluconeogenesis, dysregulation in FA metabolism related to obesity. | [30] |
Palmitate | 0.4 mmol/l palmitate | Pancreatic beta cell line and diabetic rats | DNA methylation | No changes in DNA methylation | No change in DNA methylation of Ins1 promoter under normal or high glucose conditions | [31] | |
Oleato-palmitate | 250 μM oleate-palmitate ratio 1:1 | Human skeletal muscle cells from severely obese women | DNA methylation | PPARδ (sites - 71 and 61 bp) | + | Changes in methylation of PPARD, increases FA uptake and oxidation, favors abnormal accumulation of lipids in oxidative tissues. | [32] |
Stearate and palmitate | 3.75 mM. Stearate-palmitate ratio 4:1 | Raw264.7 macrophage cell line | DNA methylation | PPARg promoter | + | Promote metabolic disorders and inflammation, increase insulin resistance and obesity. | [33] |