Milk protein synthesis is regulated by T1R1/T1R3, a G protein-coupled taste receptor, through the mTOR pathway in the mouse mammary gland

Liu, Junqiang; Wang, Yanhong; Li, Dewei; Li, Menglu; Chen, Caifa; Fang, Xingtang; Chen, Hong; Zhang, Chunlei

doi:10.1002/mnfr.201601017

Cited by 25 publications

(18 citation statements)

References 39 publications

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“…The effect of lactation in the yak mammary gland by upregulating several AAT and their potential control of mTOR signaling through the import of AA into cells underscores an essential role of AAT in yak mammary gland physiology. The expression of several AAT discussed above appears to be regulated by mTOR, suggesting the crucial importance of this pathway in milk protein synthesis, which has been demonstrated previously (Liu et al, 2017).…”

Section: Short Communication: Characterization Of Gene Expression Prosupporting

confidence: 64%

“…These 2 AAT have a regulatory relationship with mTOR, and consequently control protein synthesis, cellular growth, and survival signaling, which might be related to cancer (Fuchs and Bode, 2005). It is reported that milk protein synthesis is regulated by T1R1/T1R3, a G protein-coupled taste receptor, through the mTOR pathway in the mouse mammary gland (Liu et al, 2017). The mTOR controls ribosome biogenesis and cell growth through several regulatory pathways.…”

Section: Short Communication: Characterization Of Gene Expression Promentioning

confidence: 99%

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Short communication: Characterization of gene expression profiles related to yak milk protein synthesis during the lactation cycle

Xia

Osorio

Yang

et al. 2018

Journal of Dairy Science

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This research assessed the gene expression patterns related to the synthesis of milk in yak, which is characterized by high fat and protein content but low yield. The yak (Bos grunniens) is one of the most crucial domestic animals in Tibetan life; however, the genetic and molecular factors underlying yak milk protein synthesis remain understudied. Yak mammary biopsies harvested during late-pregnancy (d −15) through the end of subsequent lactation (d 1, 15, 30, 60, 180, and 240) were used to evaluate gene expression via real-time quantitative PCR. The expression pattern of 41 genes encompassing multiple pathways integral to milk protein synthesis including insulin, mammalian target of rapamycin (mTOR), 5′ AMP-activated protein kinase, Jak2-Stat5 signaling, and the expression of glucose and AA transporters was evaluated. Our results confirmed that most upregulated genes increased from d −15 and peaked at d 30 or 60 and then remained relatively highly expressed. Specifically, there was an increased expression of mTOR-related amino acid transporters (SLC1A5, SLC7A5, and SLC36A1), glucose transporters (SLC2A1, SLC2A3, and SLC2A8), Jak2-Stat5 pathway (ELF5), and insulin signaling pathway components (IRS1, PDPK1, and AKT1). For activation of proteins synthesis, MTOR was significantly increased only at d 1. Among inhibitors of mTOR signaling, TSC1 and PRKAA2 were significantly upregulated during lactation. The RPL23 was downregulated among ribosomal components. In conclusion, a critical role for AA and glucose transporters and insulin signaling through mTOR for regulation of yak milk protein synthesis was revealed in this study of the yak mammary gland.

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Section: Short Communication: Characterization Of Gene Expression Prosupporting

confidence: 64%

Section: Short Communication: Characterization Of Gene Expression Promentioning

confidence: 99%

Short communication: Characterization of gene expression profiles related to yak milk protein synthesis during the lactation cycle

Xia

Osorio

Yang

et al. 2018

Journal of Dairy Science

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“…The AA sensory function of the mTOR pathway was first demonstrated in a study of hepatocyte autophagy by Blommaart et al [8], who showed that addition of AA inhibited valine release as a result of autophagic protein degradation and the effect was inhibited by rapamycin. Recently, the mTOR pathway has been shown to be critical for AA sensing and utilization in the lactating bovine or mouse MG [9,10].…”

Section: Introductionmentioning

confidence: 99%

AMPK-mTOR pathway is involved in glucose-modulated amino acid sensing and utilization in the mammary glands of lactating goats

Cai

Wang

Zhao

et al. 2020

J Animal Sci Biotechnol

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Background: The local supply of energy-yielding nutrients such as glucose seems to affect the synthesis of milk components in the mammary gland (MG). Thus, our study was conducted to investigate the effects of locally available MG glucose supply (LMGS) on amino acid (AA) sensing and utilization in the MG of lactating dairy goats. Six dosages of glucose (0, 20, 40, 60, 80, and 100 g/d) were infused into the MG through the external pudendal artery to investigate the dose-dependent changes in mammary AA uptake and utilization (Exp.1) and the changes in mRNA and protein expression of the AMPK-mTOR pathway (Expt.2). Results: In Exp.1, total milk AA concentration was highest when goats were infused with 60 g/d glucose, but lower when goats were infused with 0 and 100 g/d glucose. Increasing LMGS quadratically changed the percentages of α S2-casein and α-lactalbumin in milk protein, which increased with infusions from 0 to 60 g/d glucose and then decreased with infusions between 60 and 100 g/d glucose. The LMGS changed the AA availability and intramammary gland AA utilization, as reflected by the mammary AA flux indexes. In Exp.2, the mRNA expression of LALBA in the MG increased quadratically with increasing LMGS, with the highest expression at dose of 60 g/d glucose. A high glucose dosage (100 g/d) activated the general control nonderepressible 2 kinase, an intracellular sensor of AA status, resulting in a reduced total milk AA concentration. Conclusions: Our new findings suggest that the lactating MG in dairy goats may be affected by LMGS through regulation of the AA sensory pathway, AA utilization and protein synthesis, all being driven by the AMPK-mTOR pathway.

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“…For decades, the weigh-suckle-weigh These experiments were repeated at least three times. Data are represented as means ± SD, * indicates the difference between mifepristone group and control group, * P < 0.05, * * P < 0.01, * * * P < 0.001. method has been more acceptable for its simple and effective evaluation of milk volume in mice (Boston et al, 2001;Liu et al, 2017). This method is also widely used in ruminants such as in goats or cattle (Mummed, 2012;Hogberg et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Mifepristone Treatment in Pregnant Murine Model Induced Mammary Gland Dysplasia and Postpartum Hypogalactia

Zhu

Jia

Ren

et al. 2020

Front. Cell Dev. Biol.

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Mammary gland dysplasia and postpartum hypogalactia often occur in humans and in the livestock breeding industry. However, their underlying mechanisms are not clear yet. Mifepristone, which has a high affinity for progesterone (P 4 ) and glucocorticoid receptors, was exploited here to induce the disorders of mammary gland development and lactation. Four strategies were devised for treating pregnant mice with mifepristone. In the first strategy, mice were administered 1.20 mg mifepristone/kg body weight (BW) on pregnancy day 4 (Pd4). In the second strategy, mifepristone was administered to mice twice, with 1.20 mg/kg BW on Pd4 and 0.40 mg/kg BW on Pd8. In the third strategy, mice were treated with a single dose of 0.40 mg mifepristone/kg BW on Pd8. In the fourth strategy, mice were administered 0.40 mg mifepristone/kg BW on Pd8 and 0.20 mg mifepristone/kg BW on Pd12. The results suggested that mifepristone administration at the dose of 1.20 mg/kg BW on Pd4 caused significant reduction in milk production on lactation day 1 (Ld1), Ld2, and Ld3, as assessed using a weighsuckle-weigh assay. Mammary β-casein expression, milk yields, litter growth rates, gland structure, and serum concentrations of 17-β estrogen (E 2 ), P 4 , prolactin (PRL), growth hormone (GH), corticosterone (CORT) and oxytocin (OT) as well as the receptors of these hormones were determined during pregnancy or lactation after performing the first (Pd4) strategy. The results demonstrated that mifepristone administration during early pregnancy decreased β-casein expression, milk yields and litter growth rates, induced fewer alveoli, enlarged alveolar lumina, and altered the levels of E 2 , P 4 , PRL, GH, CORT, and OT as well as the mRNA expression of these hormonal receptors during pregnancy or early lactation. The present study on pregnant mice treated with mifepristone offers an innovative murine model to study the mechanism underlying mammary gland dysplasia and postpartum hypogalactia.

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Milk protein synthesis is regulated by T1R1/T1R3, a G protein-coupled taste receptor, through the mTOR pathway in the mouse mammary gland

Abstract: T1R1/T1R3 modulates the mTOR pathway to regulate milk protein synthesis in the mouse mammary gland in vivo.

Cited by 25 publications

References 39 publications

Short communication: Characterization of gene expression profiles related to yak milk protein synthesis during the lactation cycle

Short communication: Characterization of gene expression profiles related to yak milk protein synthesis during the lactation cycle

AMPK-mTOR pathway is involved in glucose-modulated amino acid sensing and utilization in the mammary glands of lactating goats

Mifepristone Treatment in Pregnant Murine Model Induced Mammary Gland Dysplasia and Postpartum Hypogalactia

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