Role of Vanin-1 Gene Methylation in Fat Synthesis in Goose Liver: Effects of Betaine and 5-Azacytidine Treatments
College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
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Author to whom correspondence should be addressed.
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Current address: Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.
Animals 2025, 15(5), 719; https://doi.org/10.3390/ani15050719
Submission received: 20 December 2024
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Revised: 18 February 2025
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Accepted: 1 March 2025
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Published: 3 March 2025
(This article belongs to the Special Issue Effects of Genotype × Environment Interaction on Welfare, Sustainability, and Quality of Poultry Production)
Simple Summary
Vanin-1 (VNN1) is a pantotheinase that hydrolyzes pantothein to form pantothenic acid (vitamin B5) and cysteamine. Betaine, an essential methyl donor in the body, plays a crucial role in maintaining normal lipid metabolism in animals. Our previous research identified VNN1 as a key candidate gene down-regulated by betaine during lipid synthesis in goose liver. However, the underlying mechanisms of VNN1 in betaine-regulated lipid synthesis in goose liver remain unclear. Therefore, this study aimed to elucidate the role of VNN1 methylation in betaine-regulated lipid synthesis in goose liver by investigating the effects of betaine and 5-Azacytidine (AZA) on serum biochemistry, enzyme activity, VNN1 gene expression, and VNN1 promoter methylation in goslings aged 35–49 days. The results demonstrated that VNN1 methylation plays a significant role in the regulation of lipid synthesis in goose liver by betaine.
Abstract
This study aimed to investigate the mediating effect of vanin-1 (VNN1) and its DNA methylation on the reduction in liver fat synthesis due to the role of betaine and 5-Azacytidine (5-AZA) in geese. Twenty-eight 35-day-old male Jiangnan white geese with similar body weight (BW) and good health conditions were randomized into four groups (seven birds per group). All the birds were housed with the same type of basal diet. The control group was treated with normal saline intraperitoneally (I.P.); the AZA group was treated I.P. with AZA (2 mg/kg); the betaine group was fed with betaine through the diet and treated I.P. with normal saline (1.2 g/kg); the AZA+betaine group was fed with betaine through the diet and treated I.P. with AZA. The results showed that the administration of AZA significantly increased serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and VNN1 enzyme activity (p < 0.05); additionally, the expression levels of the molecules in various tissues were up-regulated to different extents, such as VNN1, fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl-CoA dehydrogenase (SCD), and sterol regulatory element binding protein (SREBP); in contrast, the treatment of betaine reduced serum TC levels and the S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio; furthermore, hepatic DNA methylation in the AZA group was decreased in terms of the VNN1 promoter region. The results demonstrated that the expression of the VNN1 gene was negatively correlated with DNA methylation. This finding verified the key role of VNN1 and its methylation in the inhibition of liver lipid synthesis by betaine and provided a novel molecular mechanism for the regulation of liver lipid metabolism.
Keywords:
VNN1 gene; DNA methylation; betaine; 5-AZA; liver fat synthesis
