Physiologic and epigenetic effects of nutrients on disease pathways

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.

A review of recent evidence of dietary protein intake and health

The Korea National Health and Nutrition Examination Survey of 2013 to 2017 reported that the average protein consumption of the Korean population is above the current recommended nutrient intake of protein proposed by the Dietary Reference Intakes for Koreans. Some health professionals and the media often advise consuming diets high in protein for promoting metabolic regulation, weight control, and muscle synthesis. However, due to lack of scientific evidence, the validity and safety of high protein consumption are yet to be fully ascertained. The present review assesses recent evidence published in 2014–2020 from human studies, focusing on adequate protein intake and protein sources for the prevention of chronic diseases, particularly metabolic disorders and sarcopenia.

2020 Korean Dietary Reference Intakes for Protein: Estimation of protein requirements and the status of dietary protein intake in the Korean population / 한국영양학회지

This article evaluated levels of Estimated Average Requirements (EARs), Reference Nutrient Intakes (RNIs), and Acceptable Macronutrient Distribution Ranges (AMDRs) of protein using the recently revised Dietary Reference Intakes (DRIs) for Koreans (2020). Dietary protein requirements are based on amounts sufficient to satisfy physiological demands to accomplish nitrogen equilibrium. The same principle was applied to estimate EARs and RNIs, for adults in DRIs conducted in 2015 and 2020 in Koreans. EAR was estimated to be 0.73 g/kg body weight/day, according to data (0.66 g/kg body weight/day) obtained using the nitrogen balance method and adjusted by efficiency of protein use (90%). RNI was calculated as EAR increased by an amount equal to twice the standard deviation of an age group so as to cover 97.5% of the group and was found to be 0.91 g/kg body weight/day. For weaned infants, children, and adolescents, growth requirement was added to estimate EAR. In particular, growth requirement was adjusted by efficiency of protein use in the revised EAR, which led to higher EARs for weaned infants, children, and adolescents of both genders as compared with 2015 DRIs. The AMDR for protein was set at 7%–20% of energy intake, which was the same as 2015 DRIs. Current, average protein intake by the Korean population is almost twice times the EAR, which suggests it might be better to increase the minimal margin for AMDR.However, it was not adjusted in this revision due to lack of evidence.

Free fatty acid-induced histone acetyltransferase activity accelerates lipid accumulation in HepG2 cells

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including PPARγ, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.

Ethanol extract of Allium fistulosum inhibits development of non-alcoholic fatty liver disease

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS: The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS: EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS: Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.