From: Fatty acids, epigenetic mechanisms and chronic diseases: a systematic review
FA | Dose | Study model | Epigenetic mechanisms | Epigenetic signature | Metabolic outcomes | Reference | |
---|---|---|---|---|---|---|---|
HUMAN | |||||||
PUFA n-3 supplementation | 3 g n-3 6-weeks | 36 overweight and obese subjects | DNA methylation | 286 CpG (93%) 22 CpG (7%) | + - | Improvement of inflammatory and immune responses, lipid metabolism, cardiovascular signaling, and diabetes pathways, reduction of plasma triglyceride and glucose levels, improved total cholesterol/HDL-cholesterol ratio. | [16] |
n-3 intake | 93 subjects were in the lowest 3 deciles of PUFA intake and 92 were in the top 3 deciles | 185 Yupik/ Alaskan native subjects | DNA methylation | 21 CpG 6 CpG | + - | Improvement of lipid metabolism, insulin sensitivity, glucose tolerance and oxidative stress. | [17] |
n-3 supplementation | MedDiet+ OOEV or MedDiet+ nuts | 12 subjects of each study group | DNA methylation | With MedDiet + nuts CPT1B/CHKB-CPT1B With MedDiet + OOEV GNASAS GNAS | + - | Benefits in health associated with changes in genes related to intermediate metabolism, diabetes, and anti-inflammatory state. | [18] |
n-3 supplementation | 6 capsules/ per day n-3 8-weeks | 7 overweight and obese women 5 control group | DNA methylation | CD14, PDK4 and FADS1 PDK4 (− 229–227) CD36 FFAR3 CpG (−18, + 33, and + 77) FFAR3 CpG (− 53 and − 202) | - + + + | Lipid metabolism, improvement of glucose tolerance and diabetes. | [19] |
n-6 intake | 40 normal-weight women | DNA methylation | TNF CpG13 and CpG19 (+ 207 + 317pb) | + | Associated with truncal fat, lipid alterations, TNF-α pathway and inflammation process. | [20] | |
Transgenerational | |||||||
DHA supplementation | 400 mg of DHA/day gestation week 18–22 to parturition. | 131 pregnant women | DNA methylation | IGF2 P3 IGF2 DMR H19 DMR | - + + | Favors expression of genes involved in growth and development. Decreases the risk to develop obesity (BMI) in infants. | [21] |
DHA supplementation | 800 mg DHA/day 20 weeks gestation to parturition. | 517 pregnant women | DNA methylation | 21 DMR | Favors appetite regulation and immune response in infants. | [22] | |
ANIMAL MODELS | |||||||
n-3 supplementation | n-3 1 g/Kg body weight every day for 12 weeks | 30 Rats | DNA methylation | % 5mC | + | Anti-colorectal cancer effect. | [23] |
n-3 supplementation | 34.9% weight as fat, 60% kcal was fish oil for 14 weeks | 12 Rats | DNA methylation, Histone methylation and acetylation | NE on methylation Histone H3 | ++ | Ameliorates leptin resistance, decreases accumulation of adipose tissue, regulating food intake and energy expenditure. | [24] |
n-3 supplementation | EPA and DHA 0.5% Gromega, pregnant pigs (150 days) and their offspring (lactation 21 days and nursery 56 days) | 5 Pigs | DNA methylation and miRNAs | Chromosome 4 DMR Intragenic region chromosome 4 and 12 | - + | Improvement of immune response, inflammation, glucose uptake, apoptosis, endoplasmic reticulum stress, insulin resistance, lipid metabolism and oxidative stress. | [25] |
IN VITRO MODELS | |||||||
n-6 AA | 1 μM 10 μM and 100 μM | Human THP-1 monocytes | DNA methylation | Dose-dependent DNA methylation A 10.5% increase in 5mC content at 100 mM compared to 1 μM dose | + | Associated with atherosclerosis, diabetes, inflammatory profile, obesity and cancer | [26] |
AA | 3 μM | Human umbilical vein endothelial cells (HUVECs) and endothelial progenitors (EPCs) | DNA methylation | Promoter region of genes KDR and Notch4 | – | Associated with changes in expression of genes implicated in carcinogenesis and angiogenesis. | [9] |
MUFA | |||||||
Oleic acid | 1 μM 10 μM and 100 μM | In vitro human THP-1 monocytes | DNA methylation | Global hypomethylation at 100 μM compared to the 1 μM dose | – | Anti-inflammatory effects. | [26] |
Oleic acid | 1–200 μM range | 20 pregnancy mice and THP-1 cells | DNA methylation | 1–50 μM but in 5 μM weaker response peaking | + | Improvement of proinflammatory profile and adipogenesis | [27] |