Corticosterone-Induced Lipogenesis Activation and Lipophagy Inhibition in Chicken Liver Are Alleviated by Maternal Betaine Supplementation

• Published in: The Journal of nutrition Vol. 148; no. 3; pp. 316 - 325
• Main Authors: Hu, Yun, Sun, Qinwei, Hu, Yan, Hou, Zhen, Zong, Yibo, Omer, Nagmeldin A, Abobaker, Halima, Zhao, Ruqian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2018; American Institute of Nutrition
• Subjects: Animals; Betaine; Betaine - pharmacology; Betaine - therapeutic use; Body mass; Chickens; Corticosterone; Corticosterone - adverse effects; Corticosterone - metabolism; Diet; Dietary Supplements; Disease Models, Animal; DNA methylation; DNA Methylation - drug effects; Eggs; Epigenesis, Genetic; epigenetic regulation; Ethanol; Fatty liver; Fatty Liver - etiology; Fatty Liver - metabolism; Fatty Liver - prevention & control; Female; Gene expression; Genes; Incubation; Lipid Metabolism - drug effects; Lipid Metabolism - genetics; Lipogenesis; Lipogenesis - drug effects; Lipogenesis - genetics; lipophagy; Liver; Liver - drug effects; Liver - metabolism; Male; Mitochondria; Mitochondrial Proteins - genetics; Offspring; Oxidation; Poultry; Pregnancy; Prenatal Nutritional Physiological Phenomena; Progeny; Promoter Regions, Genetic; Receptors, Glucocorticoid - metabolism; Transcription activation; Triglycerides - metabolism; B; NAFLD; C; mtDNA; fatty liver; lipogenesis; ChIP; epigenetic regulation; ACACA; HSD11B2; LAMP1; ATG7; MeDIP; SREBF1; CPT1A; lipophagy; GR; MAP1LC3; CORT; HSD11B1a; SCD; FASN; VEH; TFAM; GRE; betaine; corticosterone
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/nxx073

We have shown previously that in ovo betaine injection can prevent nonalcoholic fatty liver induced by glucocorticoid exposure in chickens; yet it remains unknown whether feeding betaine to laying hens may exert similar effects in their progeny. In this study, we fed laying hens a betaine-supplemented diet, and the progeny were later exposed chronically to corticosterone (CORT) to test hepatoprotective effects and further elucidate underlying mechanisms. Rugao yellow-feathered laying hens (n = 120) were fed a basal (control, C) diet or a 0.5% betaine-supplemented (B) diet for 28 d before their eggs were collected for incubation. At 49 d of age, male chickens selected from each group were daily injected subcutaneously with solvent (15% ethanol; vehicle, VEH) or CORT (4.0 mg/kg body mass) for 7 d to establish a fatty liver model. Chickens in the 4 groups (C-VEH, C-CORT, B-VEH, and B-CORT) were killed at day 57. Plasma and hepatic triglyceride (TG) concentrations, as well as the hepatic expression of genes involved in lipogenesis and lipophagy, were determined. CORT induced a 1.6-fold increase in the plasma TG concentration (P < 0.05) and a 1.8-fold increment in the hepatic TG concentration (P < 0.05), associated with activation of lipogenic genes (70–780%). In contrast, lipophagy and mitochondrial β-oxidation genes were inhibited by 30–60% (P < 0.05) in CORT-treated chickens. These CORT-induced changes were completely normalized by maternal betaine supplementation or were partially normalized to intermediate values that were significantly different from those in the C-VEH and C-CORT groups. These effects were accompanied by modifications in CpG methylation and glucocorticoid receptor binding to the promoters of major lipogenic and lipophagic genes (P < 0.05). These results indicate that maternal betaine supplementation protects male juvenile chickens from CORT-induced TG accumulation in the liver via epigenetic modulation of lipogenic and lipophagic genes.