Nutr Res Pract.  2023 Feb;17(1):13-31. 10.4162/nrp.2023.17.1.13.

Physiologic and epigenetic effects of nutrients on disease pathways

• Park SH
• Lee J
• Hwang JT
• Chung MY

• KMID: 2539447
• DOI: http://doi.org/10.4162/nrp.2023.17.1.13

Abstract

BACKGROUND/OBJECTIVES
Epigenetic regulation by nutrients can influence the development of specific diseases. This study sought to examine the effect of individual nutrients and nutrient families in the context of preventing chronic metabolic diseases via epigenetic regulation. The inhibition of lipid accumulation and inflammation by nutrients including proteins, lipids, vitamins, and minerals were observed, and histone acetylation by histone acetyltransferase (HAT) was measured. Correlative analyses were also performed.
MATERIALS/METHODS
Nutrients were selected according to information from the Korean Ministry of Food and Drug Safety. Selected nutrient functionalities, including the attenuation of fatty acid-induced lipid accumulation and lipopolysaccharide-mediated acute inflammation were evaluated in mouse macrophage Raw264.7 and mouse hepatocyte AML-12 cells. Effects of the selected nutrients on in vitro HAT inhibition were also evaluated.
RESULTS
Nitric oxide (NO) production correlated with HAT activity, which was regulated by the amino acids group, suggesting that amino acids potentially contribute to the attenuation of NO production via the inhibition of HAT activity. Unsaturated fatty acids tended to attenuate inflammation by inhibiting NO production, which may be attributable to the inhibition of in vitro HAT activity. In contrast to water-soluble vitamins, the lipid-soluble vitamins significantly decreased NO production. Water- and lipid-soluble vitamins both exhibited significant inhibitory activities against HAT. In addition, calcium and manganese significantly inhibited lipid accumulation, NO production, and HAT activity.
CONCLUSIONS
Several candidate nutrients and their family members may have roles in the prevention of diseases, including hepatic steatosis and inflammation-related diseases (i.e., nonalcoholic steatohepatitis) via epigenetic regulation. Further studies are warranted to determine which specific amino acids, unsaturated fatty acids and lipid-soluble vitamins or specific minerals influence the development of steatosis and inflammatory-related diseases.

Keyword

Obesity; acetylation; nutrients; inflammation; nitric oxide

Figure

• 

  Fig. 1 Effect of nutrients on lipid accumulation (A), NO production (B), and HAT activity (C), visualized by heatmap (D). (A) Lipid accumulation was measured by ORO staining and quantification in OPA-treated AML-12 cells. ‘(B) NO production was measured using Griess reagent in LPS-treated Raw264.7 macrophage cells. (C) In vitro HAT activity was measured using a commercially-available kit.NO, nitric oxide; HAT, histone acetyltransferase; ORO, oil red O; NC, normal control; OPA, oleic-palmitic acid; LPS, lipopolysaccharide; PC, positive control; NE, nuclear extract.***P < 0.001: significant difference between (A) NC and OPA, (B) NC and LPS. ##P < 0.01, ###P < 0.001: significant difference between (A) OPA and OPA with nutrients treatment, (B) LPS and LPS with nutrients treatment, (C) NE and NE with nutrients treatment.

• 

  Fig. 2 Lipid accumulation, NO production, and HAT activity (A) were evaluated and compared in terms of total, polar, and non-polar amino acid groups. All experiments were performed in triplicate and correlation analysis was performed (B-D). Correlation between lipid accumulation and NO production (B), lipid accumulation and HAT activity (C), and NO production and HAT activity (D) regulated by total amino acids.NO, nitric oxide; HAT, histone acetyltransferase; NC, normal control; OPA, oleic-palmitic acid; LPS, lipopolysaccharide; PC, positive control.***P < 0.001: significant difference between the NC and PC (either OPA or LPS treatment). # P < 0.05, ## P < 0.01: significant difference between PC and amino acid treatment.

• 

  Fig. 3 Lipid accumulation, NO production, and HAT activity (A) were evaluated and compared in terms of total, saturated, and unsaturated fatty acid groups. All experiments were performed in triplicate. Correlation analysis was performed (B-E). Correlation between lipid accumulation and NO production (B), lipid accumulation and HAT activity (C), and NO production and HAT activity (D) regulated by total fatty acids. Correlation between NO production and HAT activity regulated by unsaturated fatty acids (E).NO, nitric oxide; HAT, histone acetyltransferase; NC, normal control; OPA, oleic-palmitic acid; LPS, lipopolysaccharide; PC, positive control.***P < 0.001: significant difference between NC and PC (either OPA or LPS treatment). #P < 0.05, ##P < 0.01: significant difference between PC and fatty acid treatment.

• 

  Fig. 4 Lipid accumulation, NO production, and HAT activity (A) were evaluated and compared in terms of total, water soluble and lipid soluble vitamins. All experiments were performed in triplicate. Correlation analysis was performed (B-D). Correlation between lipid accumulation and HAT activity (B), NO production and HAT activity (C), and lipid accumulation and NO production (D) regulated by total vitamins.NO, nitric oxide; HAT, histone acetyltransferase; NC, normal control; OPA, oleic-palmitic acid; LPS, lipopolysaccharide; PC, positive control.***P < 0.001: significant difference between the NC and PC (either OPA or LPS treatment). #P < 0.05, ##P < 0.01: significant difference between PC and vitamin treatment.

• 

  Fig. 5 Lipid accumulation (A), NO production (B), and HAT activity (C) regulated by individual minerals. (A) Lipid accumulation was measured by ORO staining and quantification in OPA-treated AML-12 cells. (B) NO production was measured using Griess reagent in LPS-treated Raw264.7 macrophage cells. (C) In vitro HAT activity was measured using a commercially-available kit. All experiments were performed in triplicate.NO, nitric oxide; HAT, histone acetyltransferase; ORO, oil red O; NC, normal control; OPA, oleic-palmitic acid; LPS, lipopolysaccharide; PC, positive control; NE, nuclear extract.***P < 0.001: significant difference between (A) NC and OPA, (B) NC and LPS. #P < 0.05, ##P < 0.01, ###P < 0.001: significant difference between (A) OPA and OPA with minerals treatment, (B) LPS and LPS with minerals treatment, (C) NE and NE with individual mineral treatment.

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