Biosynthesis of milk fat, protein, and lactose: roles of transcriptional and posttranscriptional regulation

Osorio, J. S.; Lohakare, J. D.; Bionaz, Massimo

doi:10.1152/physiolgenomics.00016.2015

Cited by 173 publications

(191 citation statements)

References 254 publications

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“…In this study, we observed that β-casein was upregulated (p < .05) and αS1-casein was downregulated (p < .05) with CO treatment. An earlier study by Osorio, Lohakare, and Bionaz (2016) showed that the overexpression of SREBP1 increased the expression of mTOR in bovine mammary epithelial cells (Osorio et al, 2016). An earlier study by Osorio, Lohakare, and Bionaz (2016) showed that the overexpression of SREBP1 increased the expression of mTOR in bovine mammary epithelial cells (Osorio et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Camellia (Camellia oleifera Abel.) seed oil promotes milk fat and protein synthesis‐related gene expression in bovine mammary epithelial cells

Zhong

Shen

Liao

et al. 2019

Food Science & Nutrition

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Camellia (Camellia oleifera Abel.) seed oil is a commonly used edible oil of China. In ancient Chinese literature, it is mentioned to be helpful for postpartum repair and lactation in women. Research on camellia seed oil (CO) as a feed additive for dairy cattle is less. We investigated the effect of CO on the expression of milk fat and protein syntheses-related genes in differentiated bovine mammary epithelial cells (MAC-T) using soybean oil (SO) as the control. The results showed that CO increased the expression of genes related to de novo synthesis of fatty acids including sterol regulatory element-binding protein 1 (SREBP1), acetyl-CoA carboxylase 1 (ACC), fatty acid synthase (FASN), lipoprotein lipase (LPL), and stearoyl-CoA desaturase (SCD) (p < .05). Among the milk protein genes analyzed, CO increased β-casein mRNA expression (p < .05) and decreased αS1-casein mRNA expression (p < .05) in MAC-T cells. CO upregulated the pathways related to milk protein synthesis with increased mRNA levels of phosphoinositide 3-kinase (PI3K), RAC-alpha serine/threonine-protein kinase (AKT1), and mammalian target of rapamycin (mTOR) (p < .05) in MAC-T cells. Ribosomal protein S6 kinase beta-1 (S6K1) gene was upregulated, and eukaryotic initiation factor 4E (eIF4E) gene (p < .05) was downregulated with CO treatment.The mRNA expression levels of janus kinase 2 (JAK2), activator of transcription 5-β (STAT5-β), and E74-like factor 5 (ELF5) were elevated in MAC-T cells treated with CO (p < .05). Meanwhile, the protein expression levels of S6K1, STAT5-β, phosphorylated mTOR (p-mTOR), p-S6K1, and p-STAT5-β increased in MAC-T cells treated with CO (p < .05). In summary, CO promoted β-casein synthesis by regulating PI3K-mTOR-S6K1 and JAK2-STAT5 signaling pathways and influenced fatty acid synthesis by regulating SREBP1-related genes in MAC-T cells. We need to further confirm the function of CO using in vivo models.

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Section: Discussionmentioning

confidence: 99%

Camellia (Camellia oleifera Abel.) seed oil promotes milk fat and protein synthesis‐related gene expression in bovine mammary epithelial cells

Zhong

Shen

Liao

et al. 2019

Food Science & Nutrition

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“…2D and 4), beginning with the transcription of their genes into mRNA, then translated in proteins and folded in the rough ER. Major milk proteins, namely caseins (a-, b-, g-, and k-caseins) also undergo posttranslational modifications [48], mostly in the Golgi, associate with calcium and phosphate to form supramolecular structures called casein micelles (~140 nm in diameter), which are packed in SVs. SVs also contain water, LTF, oligosaccharides, and high concentration of lactose, phosphate, calcium and citrate.…”

Section: Transcellular Pathwaysmentioning

confidence: 99%

Physiology of milk secretion

Truchet

Honvo-Houeto

2017

Best Practice & Research Clinical Endocrinology & Metab

100

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“…A, Western blotting was performed to determine the effects of U2AF65 overexpression and knockdown on mTOR phosphorylation and SREBP-1c protein levels. 13,14 In this study, we observed that U2AF65 positively regulates milk fat synthesis, cell growth, and mRNA and protein levels of SREBP-1c. C, Relative protein levels of SREBP-1c/β-actin were analysed by grey scale scan.…”

Section: Discussionmentioning

confidence: 56%

“…10,11 Sterol regulatory element-binding transcription protein 1 (SREBP-1) is a transcription factor that plays a key role in the regulation of cholesterol biosynthesis and fatty acid metabolism, particularly in the biosynthesis of lipids. 1,2 It is well established that the mTOR complex 1 (mTORC1) controls the activity 13,14 of SREBP-1. In addition, the mTOR-SREBP-1c pathway has been confirmed to be a central pathway that controls the synthesis of milk protein, milk fat, and lactose and regulates the growth of BMECs.…”

mentioning

confidence: 99%

U2AF65 enhances milk synthesis and growth of bovine mammary epithelial cells by positively regulating the mTOR‐SREBP‐1c signalling pathway

Zhen

et al. 2019

Cell Biochemistry & Function

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U2 snRNP auxiliary factor 65 kDa (U2AF65) is a splicing factor that promotes prespliceosome assembly. The function of U2AF65 in alternative splicing has been identified; however, the essential physiological role of U2AF65 remains poorly understood. In this study, we investigated the regulatory role of U2AF65 in milk synthesis and growth of bovine mammary epithelial cells (BMECs). Our results showed that U2AF65 localizes in the nucleus. Treatment with amino acids (Met and Leu) and hormones (prolactin and β-estradiol) upregulated the expression of U2AF65 in these cells. U2AF65 overexpression increased the synthesis of β-casein, triglycerides, and lactose; increased cell viability; and promoted proliferation of BMECs. Furthermore, our results showed that U2AF65 positively regulated mTOR phosphorylation and expression of mature mRNA of mTOR and SREBP-1c. Collectively, our findings demonstrate that U2AF65 regulates the mRNA expression of signalling molecules (mTOR and SREBP-1c) involved in milk synthesis and growth of BMECs, possibly via controlling the splicing and maturation of these mRNAs. U2 snRNP auxiliary factor 65 kDa (U2AF65) is a splicing factor that promotes prespliceosome assembly. The essential physiological role of U2AF65 remains poorly understood. In the present study, we confirmed that U2AF65 functions as a positive regulator of milk synthesis in and proliferation of bovine mammary epithelial cells via the mTOR-SREBP-1c signalling pathway. Therefore, our study uncovers the regulatory role of U2AF65 in milk synthesis and cell proliferation. KEYWORDS U2AF65, mTOR, SREBP-1c, β-casein, triglyceride, lactose 1 | INTRODUCTION U2 small nuclear ribonucleoprotein (U2snRNP) auxiliary factor (U2AF) is a conserved nuclear factor that plays a crucial role in mRNA splicing. U2AF is a stable heterodimer comprising U2AF65 subunit (65 kDa), which is encoded by U2AF2 gene, and the U2AF35 (35 kDa) subunit, which is encoded by the U2AF1 gene. U2AF65 interacts with the polypyrimidine tract (PPT), a conserved 3′ splice-site (ss) immediately downstream of the branch point sequence (BPS). On the other hand, U2AF35 interacts with invariant AG dinucleotides at the 3′ ss and stabilizes the binding of U2AF65 with RNA. 1,2A series of U2AF mutations have been characterized to investigate the functions of U2AF as a splicing factor, and previous studies have revealed that the stoichiometry of U2AF is important for accurate 3′ ss selection. 3,4 Consistent with the disease phenotype of myelodysplasia, one study indicated that mutations in U2AF cause widespread changes in alternative splicing and is linked to decreased cell proliferation. 5 U2AF has also been reported to be involved in other cellular processes, such as mRNA export, in which it binds to

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Biosynthesis of milk fat, protein, and lactose: roles of transcriptional and posttranscriptional regulation

Abstract: Osorio JS, Lohakare J, Bionaz M. Biosynthesis of milk fat, protein, and lactose: roles of transcriptional and posttranscriptional regulation.

Cited by 173 publications

References 254 publications

Camellia (Camellia oleifera Abel.) seed oil promotes milk fat and protein synthesis‐related gene expression in bovine mammary epithelial cells

Camellia (Camellia oleifera Abel.) seed oil promotes milk fat and protein synthesis‐related gene expression in bovine mammary epithelial cells

Physiology of milk secretion

U2AF65 enhances milk synthesis and growth of bovine mammary epithelial cells by positively regulating the mTOR‐SREBP‐1c signalling pathway

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