Integrative network analysis revealed the molecular function of folic acid on immunological enhancement in a sheep model

Abstract

We previously observed the beneficial role of folic acid supplemented from maternal or offspring diet on lamb growth performance and immunity. Twenty-four Hu lambs from four groups (mother received folic acid or not, offspring received folic acid or not) were used in the current study, which was conducted consecutively to elucidate the molecular regulatory mechanisms of folic acid in lambs by analyzing blood metabolome, liver transcriptome, and muscle transcriptome. Serum metabolomics analysis showed that L-homocitrulline, hyodeoxycholic acid, 9-Hpode, palmitaldehyde, N-oleoyl glycine, hexadecanedioic acid, xylose, 1,7-dimethylxanthine, nicotinamide, acetyl-N-formyl-5-methoxykynurenamine, N6-succinyl adenosine, 11-cis-retinol, 18-hydroxycorticosterone, and 2-acetylfuran were down-regulated and methylisobutyrate was up-regulated by the feeding of folic acid from maternal and/or offspring diets. Meanwhile, folic acid increased the abundances of S100A12 and IRF6 but decreased TMEM25 in the liver. In the muscle, RBBP9, CALCR, PPP1R3D, UCP3, FBXL4, CMBL, and MTFR2 were up-regulated, CYP26B1 and MYH9 were down-regulated by the feeding of folic acid. The pathways of bile secretion, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and herpes simplex virus 1 infection were changed by folic acid in blood, liver, or muscle. Further integrated analysis revealed potential interactions among the liver, blood, and muscle, and the circulating metabolites, hub gene, and pathways, which might be the predominant acting targets of folic acid in animals. These findings provide fundamental information on the beneficial function of folic acid no matter from maternal or offspring, in regulating animal lipid metabolism and immune enhancement, providing a theoretical basis for the use of folic acid from the view of animal health care.

Enhancing bovine immune, antioxidant and anti-inflammatory responses with vitamins, rumen-protected amino acids, and trace minerals to prevent periparturient mastitis

“…The existing body of published evidence strongly supports the notion that folic acid supplementation yields notable improvements in metabolic function (167), while also playing a crucial role in preventing oxidative stress and enhancing immune responses (168) in periparturient dairy cattle (169). The period around calving presents a vulnerability to lowered immunity in dairy cattle due to folic acid deficiency (165).…”

The causal relationship of human blood metabolites with the components of Sarcopenia: a two-sample Mendelian randomization analysis

“…Isobutyrylcarnitine is a metabolic product that occurs during the transfer of acyl residues from isobutyryl coenzyme A to carnitine [ 27 ]. Previous studies have shown that higher levels of hydroxylated acylcarnitine was negatively correlated with the decline in grip strength in a short term [ 34 ], while medium and long-chain acylcarnitines were correlated with a poorer physical function [ 28 ]. Acylcarnitine, disrupting peroxisomal or mitochondrial oxidation processes [ 29 ], also plays a part in mitochondrial function, whose dysregulation is highly involved in the pathological loss of skeletal muscle mass and function in the elderly [ 30 ].…”

“…Hyodeoxycholate, androsterone sulfate and glycine have also been identified as certain specific metabolites in relation to muscle health in the current study. Hyodeoxycholate is a bile acid derivative, and a negative correlation between blood hyodeoxycholic acid and muscle uncoupling protein 3 gene was found, suggesting a potential impact on muscle function [ 34 ]. Androsterone sulfate is one metabolite of androgens, which may also be associated with the change of lean body mass and muscle mass [ 35 ].…”

Folic Acid and Taurine Alleviate the Impairment of Redox Status, Immunity, Rumen Microbial Composition and Fermentation of Lambs under Heat Stress

“…It was reported that the supplement of folic acid at 1.5 mg/kg significantly improved the broilers' total antioxidant capacity (T-AOC), catalase enzyme activity (CAT), and superoxide dismutase (SOD) [14]. Also, a folic acid supplement in diet was beneficial for maternal or offsprings' immune status in a sheep model [16]. Another study showed that dietary-coated folic acid improved rumen fermentation, nutrient digestibility, and growth performance in bulls [17].…”