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In Ovo injection of betaine affects hepatic cholesterol metabolism through epigenetic gene regulation in newly hatched chicks.

ABSTRACT: Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations.

SUBMITTER: Hu Y

PROVIDER: S-EPMC4393024 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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In Ovo injection of betaine affects hepatic cholesterol metabolism through epigenetic gene regulation in newly hatched chicks.

Hu Yun Y Sun Qinwei Q Li Xiaoliang X Wang Min M Cai Demin D Li Xi X Zhao Ruqian R

PloS one 20150410 4

Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the ...[more]

PMID: 25860502

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Project description:Corticosterone is critical for the maturation and survival of chicken fetus around hatching. Betaine is used as a feed additive in poultry industry to promote growth and mitigate stress. However, it remains unknown whether betaine could affect adrenal corticosterone synthesis in pre-hatching chicken fetuses. In this study, betaine (2.5 mg/egg) was injected into developing chicken fetuses at d 11 of incubation (E11) and its impact on adrenal steroidogenesis was investigated at day 19 (E19). Plasma corticosterone concentration was significantly (P < 0.05) elevated in betaine-treated fetuses, together with increased adrenal expression of melanocortin 2 receptor and steroidogenic acute regulatory protein. Accordingly, the corticosterone biosynthetic enzymes, such as cytochrome P450 family 11 subfamily A member 1, 3β-hydroxysteroid dehydrogenase and cytochrome P450 family 21 subfamily A member 2, as well as cholesterol biosynthesis or regulation-related genes, such as sterol regulatory element-binding protein 1, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and low-density lipoprotein receptor, were all significantly (P < 0.05) upregulated in betaine group. Meanwhile, steroidogenic factor-1 and glucocorticoid receptor were significantly (P < 0.05) enhanced, whereas expression of dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome gene, a nuclear receptor known as a repressor of adrenal steroidogenesis, was significantly (P < 0.05) downregulated. Betaine significantly (P < 0.05) increased adrenal expression of genes involved in one-carbon metabolism and DNA methylation, such as S-adenosyl homocysteine hydrolase, betaine-homocysteine-methyltransferase, methionine adenosyl transferase and DNA methyltransferases, yet the promoter regions of most steroidogenic genes were significantly (P < 0.05) hypomethylated. These results indicate that in ovo injection of betaine promotes adrenal glucocorticoid synthesis in chicken fetuses before hatching, which involves alterations in DNA methylation.

Project description:The purpose of this study was to investigate whether in ovo feeding of t10,c12-conjugated linoleic acid (CLA) could regulate hepatic lipid metabolism and decrease lipid accumulation in newly hatched chicks. Three hundred and sixty fertilely specific pathogen-free hatching eggs were selected and randomly divided into 6 groups. On embryonic day 11 of incubation (E11), 0, 1.5, 3.0, 4.5, 6.0, or 7.5 mg t10,c12-CLA were injected into the eggs. The results indicated that in ovo feeding of t10,c12-CLA significantly decreased the subcutaneous adipose tissue (SAT) mass and the relative SAT weight of newly hatched chicks in linear and quadratic manners (P < 0.05). In liver, the levels of triglycerides were reduced linearly and quadratically and total cholesterol were reduced quadratically as the dose of t10,c12-CLA increased (P < 0.05). Meanwhile, the hepatic carnitine palmitoyltransferase-1a (CPT1a) content and polyunsaturated fatty acid proportion were increased quadratically in t10,c12-CLA groups (P < 0.05), accompanied by the decrease of malondialdehyde level and the increase of glutathione peroxidase and total antioxidant capacity activities (P < 0.05). In addition, in ovo feeding of t10,c12-CLA decreased the mRNA expression levels of fatty acid synthase, acetyl-CoA carboxylase 1 in linear and quadratic manners (P < 0.05), and decreased the mRNA expression of adipose triacylglyceride lipase and stearoyl-CoA desaturase significantly in liver (P < 0.05), accompanied by upregulating the mRNA expression of CPT1a quadratically and AMP-activated protein kinase α linearly and quadratically (P < 0.05). In SAT, the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) and sterol regulatory element-binding protein-1c were decreased linearly and quadratically (P < 0.05), and the expression of PPARα and CPT1a genes were increased linearly and quadratically as the dose of t10,c12-CLA increased (P < 0.05). In conclusion, our findings demonstrate that in ovo feeding of t10,c12-CLA alleviates lipid accumulation in newly hatched chicks by suppressing fatty acid synthesis and stimulating lipolysis in the liver and inhibiting adipocyte differentiation in subcutaneous adipose tissue.

Project description:The first third of incubation is critical for embryonic development, and environmental changes during this phase can affect the physiology and survival of the embryos. We evaluated the effects of low (LT), control (CT), and high (HT) temperatures during the first 5 days of incubation on ventilation ( V. E ), body temperature (Tb), oxygen consumption ( V. O2), respiratory equivalent ( V. E / V. O2), and brain monoamines on 3-days-old (3d) and 14-days-old (14d) male and female chickens. The body mass of LT animals of both ages and sexes was higher compared to HT and CT animals (except for 3d males). The heart mass of 14d HT animals was higher than that of CT animals. Thermal manipulation did not affect V. E , V. O2 or V. E / V. O2 of 3d animals in normoxia, except for 3d LT males V. E , which was lower than CT. Regarding 14d animals, the HT females showed a decrease in V. E and V. O2 compared to CT and LT groups, while the HT males displayed a lower V. O2 compared to CT males, but no changes in V. E / V. O2. Both sexes of 14d HT chickens presented a greater Tb compared to CT animals. Thermal manipulations increased the dopamine turnover in the brainstem of 3d females. No differences were observed in ventilatory and metabolic parameters in the 3d animals of either sexes, and 14d males under 7% CO2. The hypercapnic hyperventilation was attenuated in the 14d HT females due to changes in V. O2, without alterations in V. E . The 14d LT males showed a lower V. E , during hypercapnia, compared to CT, without changes in V. O2, resulting in an attenuation in V. E / V. O2. During hypoxia, 3d LT females showed an attenuated hyperventilation, modulated by a higher V. O2. In 14d LT and HT females, the increase in V. E was greater and the hypometabolic response was attenuated, compared to CT females, which resulted in no change in the V. E / V. O2. In conclusion, thermal manipulations affect hypercapnia-induced hyperventilation more so than hypoxic challenge, and at both ages, females are more affected by thermal manipulation than males.

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In Ovo injection of betaine affects hepatic cholesterol metabolism through epigenetic gene regulation in newly hatched chicks.

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In Ovo injection of betaine affects hepatic cholesterol metabolism through epigenetic gene regulation in newly hatched chicks.

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