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Table 1 Effects of unsaturated fatty acids on metabolic outcomes through epigenetic mechanisms

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]

  1. FA Fatty acids, PUFA Polyunsaturated fatty acids, n-3 linolenic acid, DHA Docosahexaenoic acid, EPA Eicosapentaenoic acid, AA Arachidonic acid, MUFA Monounsaturated fatty acid, TNF Tumor necrosis factor
  2. DMR Differentially methylated regions
  3. NE No-effect on DNA methylation
  4. + hypermethylated
  5. - hypomethylated
  6. ++ Hyperacetylation