miR-34a-5p Increases Hepatic Triglycerides and Total Cholesterol Levels by Regulating ACSL1 Protein Expression in Laying Hens

Tian, Weihua; Wang, Zhang; Yue, Ya-Xin; Li, Hong; Li, Zhuanjian; Han, Ruili; Tian, Yadong; Kang, Xiangtao; Liu, Xiaojun

doi:10.3390/ijms20184420

Cited by 23 publications

(21 citation statements)

References 49 publications

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“…With the start of laying, a sharp raised EBP-like expression level in liver was observed from pre-laying stage (20 weeks old) to peak-laying hens (30 weeks old). A same rising trend of cholesterol levels was previously found in laying hens ( Tian et al, 2019 ). The present results were consistent with previous studies and further supported our hypothesis that EBP-like playing the same role in cholesterol biosynthesis in chickens.…”

Section: Discussionsupporting

confidence: 86%

Evolution, Expression Profile, Regulatory Mechanism, and Functional Verification of EBP-Like Gene in Cholesterol Biosynthetic Process in Chickens (Gallus Gallus)

Jiang

Wang

et al. 2021

Front. Genet.

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The emopamil binding protein (EBP) is an important enzyme participating in the final steps of cholesterol biosynthesis in mammals. A predictive gene EBP-like, which encodes the protein with a high identity to human EBP, was found in chicken genome. No regulatory mechanisms and biological functions of EBP-like have been characterized in chickens. In the present study, the coding sequence of EBP-like was cloned, the phylogenetic trees of EBP/EBP-like were constructed and the genomic synteny of EBP-like was analyzed. The regulatory mechanism of EBP-like were explored with in vivo and in vitro experiments. The biological functions of EBP-like in liver cholesterol biosynthetic were examined by using gain- or loss-of-function strategies. The results showed that chicken EBP-like gene was originated from a common ancestral with Japanese quail EBP gene, and was relatively conservative with EBP gene among different species. The EBP-like gene was highly expressed in liver, its expression level was significantly increased in peak-laying stage, and was upregulated by estrogen. Inhibition of the EBP-like mRNA expression could restrain the expressions of EBP-like downstream genes (SC5D, DHCR24, and DHCR7) in the cholesterol synthetic pathway, therefore downregulate the liver intracellular T-CHO level. In conclusion, as substitute of EBP gene in chickens, EBP-like plays a vital role in the process of chicken liver cholesterol synthesis. This research provides a basis for revealing the molecular regulatory mechanism of cholesterol synthesis in birds, contributes insights into the improvement of the growth and development, laying performance and egg quality in poultry.

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Section: Discussionsupporting

confidence: 86%

Evolution, Expression Profile, Regulatory Mechanism, and Functional Verification of EBP-Like Gene in Cholesterol Biosynthetic Process in Chickens (Gallus Gallus)

Jiang

Wang

et al. 2021

Front. Genet.

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“…The knockdown of miR-34a can inhibit lipid accumulation and reduce liver cell steatosis [64]. In chicken liver, miR-34a-5p promotes the accumulation of TG by regulating the expression of long-chain acyl-CoA synthetase 1 (ACSL1), and it has a function similar to that of human and mouse hepatocytes, thus achieving the positive regulation of fatty acid synthesis [65]. Interestingly, miR-221-5p was highly conserved among species including mammals, and gga-miR-221-5p was involved in liver lipid metabolism; our study results may also provide a valuable reference for humans in lipid study.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Abolishes the Repression Role of gga-miR-221-5p Targeting ELOVL6 and SQLE to Promote Lipid Synthesis in Chicken Liver

Zhang

Wang

et al. 2020

IJMS

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Few studies have been conducted regarding the biological function and regulation role of gga-miR-221-5p in the liver. We compared the conservation of miR-221-5p among species and investigated the expression pattern of gga-miR-221-5p, validating the direct target genes of gga-miR-221-5p by dual luciferase reporter assay, the biological function of gga-miR-221-5p in the liver was studied by gga-miR-221-5p overexpression and inhibition. Furthermore, we explored the regulation of gga-miR-221-5p and its target genes by treatment with estrogen and estrogen antagonists in vivo and in vitro. The results showed that miR-221-5p was highly conserved among species, expressed in all tested tissues and significantly downregulated in peak-laying hen liver compared to pre-laying hen liver. Gga-miR-221-5p could directly target the expression of elongase of very long chain fatty acids 6 (ELOVL6) and squalene epoxidase (SQLE) genes to affect triglyceride and total cholesterol content in the liver. 17β-estradiol could significantly inhibit the expression of gga-miR-221-5p but promote the expression of ELOVL6 and SQLE genes. In conclusion, the highly conservative gga-miR-221-5p could directly target ELOVL6 and SQLE mRNAs to affect the level of intracellular triglyceride and total cholesterol. Meanwhile, 17β-estradiol could repress the expression of gga-miR-221-5p but increase the expression of ELOVL6 and SQLE, therefore promoting the synthesis of intracellular triglyceride and cholesterol levels in the liver of egg-laying chicken.

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“…Long-chain acyl-CoA synthetase (ACSL) is a candidate gene for the regulation of skeletal muscle fatty acid composition [ 15 ] and catalyzes the conversion of long-chain fatty acids into acyl-CoA [ 46 ]. ACSL1 as a dominating family member, is involved in multiple lipid metabolism pathways, including biosynthesis of unsaturated fatty acids, PPAR signaling, and fatty acid metabolism pathways [ 14 ].…”

Section: Important Genes Involved In Chicken Fat Metabolismmentioning

confidence: 99%

“…MiR-34a-5p, a member of the miR-34a family, is responsible for increasing the intracellular levels of TG, as well as total cholesterol in hepatocytes by inhibiting the translation of its target gene, ACSL1, in chicken livers. It is indicated that miR-34a-5p has a significantly higher expression level in the liver of peak laying hens compared with prelaying hens and closely related to lipid metabolism [ 46 ]. Besides, the differential expression analysis of miRNAs in Gushi chicken breast muscle at different development stages showed that miR-34a-3p is a stage-specific miRNA that was abundantly expressed at 30 weeks of chicken age [ 15 ].…”

Section: Chicken Mirnasmentioning

confidence: 99%

Molecular Regulation of Lipogenesis, Adipogenesis and Fat Deposition in Chicken

Nematbakhsh

Chong

Selamat

et al. 2021

Genes

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In the poultry industry, excessive fat deposition is considered an undesirable factor, affecting feed efficiency, meat production cost, meat quality, and consumer’s health. Efforts to reduce fat deposition in economically important animals, such as chicken, can be made through different strategies; including genetic selection, feeding strategies, housing, and environmental strategies, as well as hormone supplementation. Recent investigations at the molecular level have revealed the significant role of the transcriptional and post-transcriptional regulatory networks and their interaction on modulating fat metabolism in chickens. At the transcriptional level, different transcription factors are known to regulate the expression of lipogenic and adipogenic genes through various signaling pathways, affecting chicken fat metabolism. Alternatively, at the post-transcriptional level, the regulatory mechanism of microRNAs (miRNAs) on lipid metabolism and deposition has added a promising dimension to understand the structural and functional regulatory mechanism of lipid metabolism in chicken. Therefore, this review focuses on the progress made in unraveling the molecular function of genes, transcription factors, and more notably significant miRNAs responsible for regulating adipogenesis, lipogenesis, and fat deposition in chicken. Moreover, a better understanding of the molecular regulation of lipid metabolism will give researchers novel insights to use functional molecular markers, such as miRNAs, for selection against excessive fat deposition to improve chicken production efficiency and meat quality.

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miR-34a-5p Increases Hepatic Triglycerides and Total Cholesterol Levels by Regulating ACSL1 Protein Expression in Laying Hens

Cited by 23 publications

References 49 publications

Evolution, Expression Profile, Regulatory Mechanism, and Functional Verification of EBP-Like Gene in Cholesterol Biosynthetic Process in Chickens (Gallus Gallus)

Evolution, Expression Profile, Regulatory Mechanism, and Functional Verification of EBP-Like Gene in Cholesterol Biosynthetic Process in Chickens (Gallus Gallus)

Estrogen Abolishes the Repression Role of gga-miR-221-5p Targeting ELOVL6 and SQLE to Promote Lipid Synthesis in Chicken Liver

Molecular Regulation of Lipogenesis, Adipogenesis and Fat Deposition in Chicken

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