Fetal betaine exposure modulates hypothalamic expression of cholesterol metabolic genes in offspring cockerels with modification of promoter DNA methylation

Abstract

In documents, maternal betaine modulates hypothalamic cholesterol metabolism in chicken posthatchings, but it remains unclear whether this effect can be passed on by generations. In present study, eggs were injected with saline or betaine at 2.5 mg/egg, and the hatchlings (F1) were raised under the same condition until sexual maturation. Both the control group and the betaine group used artificial insemination to collect sperm from their cockerels. Fertilized eggs were incubated, and the hatchlings of the following generation (F2) were raised up to 64 D of age. F2 cockerels in betaine group showed significantly ( P < 0.05) lower body weight, which was associated with significantly decreased ( P < 0.05) hypothalamic content of total cholesterol and cholesterol ester. Concordantly, hypothalamic expression of cholesterol biosynthetic genes, SREBP2 and HMGCR , were significantly downregulated ( P < 0.05), together with cholesterol conversion-related and excretion-related genes, CYP46A1 and ABCA1 . These changes coincided with a significant downregulation in mRNA expression of regulatory neuropeptides including brain-derived neurotrophic factor, neuropeptide Y, and corticotropin-releasing hormone. Moreover, genes involved in methyl transfer cycle were also modified. Betaine homocysteine methyltransferase ( P < 0.05) was downregulated, yet DNA methyltransferase1 tended to be upregulated ( P = 0.06). S-adenosyl methionine/S-adenosylhomocysteine ratio was higher in the hypothalamus of betaine-treated F2 cockerels, which was associated with significantly modified CpG methylation on the promoter of those affected genes. These results suggested that betaine might regulate central cholesterol metabolism and hypothalamic expression of genes related to brain function by altering promoter DNA methylation in F2 cockerels.

Beneficial Effects of Betaine: A Comprehensive Review

“…They also reported betaine has an anti-nociceptive and a sedative role through interactions with opioidergic and γ-aminobutyric acid (GABA) receptors [ 220 ]. In cockerels (young roosters), betaine affected the central cholesterol metabolism by decreasing the hypothalamic content of total cholesterol and cholesterol esters and downregulating the expression of cholesterol biosynthetic genes related to brain function [ 221 ].…”

Betaine supplementation alleviates corticosterone-induced hepatic cholesterol accumulation through epigenetic modulation of HMGCR and CYP7A1 genes in laying hens

“… Hu et al (2017b) reported that prenatal betaine prevented CORT-induced decrease in hepatic CYP27A1 mRNA expression associated with its promoter DNA methylation in offspring male chickens. Idriss et al (2020) reported that prenatal betaine administration modulated hypothalamic mRNA abundance of HMGCR by altering its promoter methylation level in offspring cockerels. Nevertheless, it is noted that the methylation status of the promoters of cholesterol metabolic genes in reaction to methyl donor is intricate and gene specific.…”

Betaine Alleviates High-Fat Diet-Induced Disruptionof Hepatic Lipid and Iron Homeostasis in Mice

“…Betaine is involved in the methionine cycle for the conversion of homocysteine to methionine, which is further converted to SAM, a universal methyl donor for numerous methylation reactions, including DNA methylation catalyzed by DNA methyltransferases (DNMTs). Numerous studies indicate the role of betaine in methyl transfer and DNA methylation [ 26 , 52 ]. In this study, GNMT and DNMT1 was decreased by HFD and restored by betaine, which implies the participation of DNA methylation in the therapeutical action of betaine on HFD-induced NAFLD.…”