Symposium review: Intravital imaging of the lactating mammary gland in live mice reveals novel aspects of milk-lipid secretion

Mather, Ian H.; Masedunskas, Andrius; Chen, Yun; Weigert, Roberto

doi:10.3168/jds.2018-15459

Cited by 27 publications

(45 citation statements)

References 125 publications

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“…Milk secretion is critical for nutrition delivery from parent to offspring. Recently, researchers developed intravital imaging procedures using transgenic mice to provide mechanistic insight into the secretion of lipid droplets within the mammary epithelium in real time, which could be applied to investigate trafficking events during lactation 48,49 . However, the Percentage of remaining mRNA (Normalized to 18S rRNA) fundamental regulation of milk secretion remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh

Zhao

Hao

et al. 2020

Nat Commun

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Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. However, the underlying molecular mechanism is less clear. Here we report that TDP-43, a RNA-binding protein, underwent positive selection in the mammalian lineage. Furthermore, TDP-43 gene (Tardbp) loss induces accumulation of large lipid droplets and severe lipid secretion deficiency in mammary epithelial cells to outside alveolar lumens, eventually resulting in lactation failure and pup starvation within three weeks postpartum. In human milk samples from lactating women, the expression levels of TDP-43 is positively correlated with higher milk output. Mechanistically, TDP-43 exerts post-transcriptional regulation of Btn1a1 and Xdh mRNA stability, which are required for the secretion of lipid droplets from epithelial cells to the lumen. Taken together, our results highlights the critical role of TDP-43 in milk lipid secretion, providing a potential strategy for the screening and intervention of clinical lactation insufficiency.

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Section: Discussionmentioning

confidence: 99%

TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh

Zhao

Hao

et al. 2020

Nat Commun

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“…CIDEA is expressed in milk-secreting epithelial cells (Wang et al., 2012; Monks et al., 2016) and is seen to aggregate at points of contact between lipid droplets in these cells (Monks et al., 2016), where it is proposed to form channels that mediate neutral lipid flow from smaller to larger droplets (Gong et al., 2011; Jambunathan et al., 2011). This concept has been beautifully demonstrated in milk-secreting epithelial cells by intravital imaging (Mather et al., 2019), which showed numerous unidirectional fusion events in which small lipid droplets are subsumed into larger ones. The CIDEA appears to remain associated with the fused droplet as large droplets accumulate a CIDEA coat that is not seen on smaller, basally localized lipid droplets (Monks, unpublished).…”

Section: Lipid Droplets Grow By Cidea-mediated Fusionmentioning

confidence: 97%

“…Although continued interaction of lipid droplets with ER allows direct synthesis to contribute to lipid droplet growth, fusion of lipid droplets in milk-secreting epithelial cells has been directly observed via intravital imaging, both within the cytoplasm and sites where lipid droplets are docked at the apical plasma membrane (Masedunskas et al., 2017; Mather et al., 2019). Cell death-inducing DFFA-like effector A (CIDEA) is a lipid droplet coat protein that has been identified as a key regulator of droplet fusion and lipid transfer in brown and white adipose (Christianson et al., 2010; Wu et al., 2014; Barneda et al., 2015).…”

Section: Lipid Droplets Grow By Cidea-mediated Fusionmentioning

confidence: 99%

Organellar Contacts of Milk Lipid Droplets

Monks

Ladinsky

McManaman

2020

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Milk-secreting epithelial cells of the mammary gland are functionally specialized for the synthesis and secretion of large quantities of neutral lipids, a major macronutrient in milk from most mammals. Milk lipid synthesis and secretion are hormonally regulated and secretion occurs by a unique apocrine mechanism. Neutral lipids are synthesized and packaged into perilipin-2 (PLIN2) coated cytoplasmic lipid droplets within specialized cisternal domains of rough endoplasmic reticulum (ER). Continued lipid synthesis by ER membrane enzymes and lipid droplet fusion contribute to the large size of these cytoplasmic lipid droplets (5-15 lm in diameter). Lipid droplets are directionally trafficked within the epithelial cell to the apical plasma membrane. Upon contact, a molecular docking complex assembles to tether the droplet to the plasma membrane and facilitate its membrane envelopment. This docking complex consists of the transmembrane protein, butyrophilin, the cytoplasmic housekeeping protein, xanthine dehydrogenase/oxidoreductase, the lipid droplet coat proteins, PLIN2, and cell death-inducing DFFA-like effector A. Interactions of mitochondria, Golgi, and secretory vesicles with docked lipid droplets have also been reported and may supply membrane phospholipids, energy, or scaffold cytoskeleton for apocrine secretion of the lipid droplet. Final secretion of lipid droplets into the milk occurs in response to oxytocinstimulated contraction of myoepithelial cells that surround milk-secreting epithelial cells. The mechanistic details of lipid droplet release are unknown at this time. The final secreted milk fat globule consists of a triglyceride core coated with a phospholipid monolayer and various coat proteins, fully encased in a membrane bilayer.

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“…The process of the secretion of milk fat globules has been previously reviewed in detail by Heid and Keenan ( 2005 ). In brief, milk TAG are produced in the endoplasmic reticulum and are released as microlipid globules that are coated by a single layer of proteins and polar lipids (Masedunskas et al, 2017 ; Mather et al, 2019 ). These droplets then move to the apical part of the cell, where some fuse together, resulting in fat globules of different sizes (Masedunskas et al, 2017 ; Mather et al, 2019 ).…”

Section: Nature-assembled Structures In Milkmentioning

confidence: 99%

“…In brief, milk TAG are produced in the endoplasmic reticulum and are released as microlipid globules that are coated by a single layer of proteins and polar lipids (Masedunskas et al, 2017 ; Mather et al, 2019 ). These droplets then move to the apical part of the cell, where some fuse together, resulting in fat globules of different sizes (Masedunskas et al, 2017 ; Mather et al, 2019 ). Interactions between the single layer of fat globules and the bilayer of the plasma membrane occur in this part of the cell, resulting in a multilamellar membrane.…”

Section: Nature-assembled Structures In Milkmentioning

confidence: 99%

Nature-Assembled Structures for Delivery of Bioactive Compounds and Their Potential in Functional Foods

2020

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Consumers are demanding more natural, healthy, and high-quality products. The addition of health-promoting substances, such as bioactive compounds, to foods can boost their therapeutic effect. However, the incorporation of bioactive substances into food products involves several technological challenges. They may have low solubility in water or poor stability in the food environment and/or during digestion, resulting in a loss of their therapeutic properties. Over recent years, the encapsulation of bioactive compounds into laboratory-engineered colloidal structures has been successful in overcoming some of these hurdles. However, several nature-assembled colloidal structures could be employed for this purpose and may offer many advantages over laboratory-engineered colloidal structures. For example, the casein micelles and milk fat globules from milk and the oil bodies from seeds were designed by nature to deliver biological material or for storage purposes. These biological functional properties make them good candidates for the encapsulation of bioactive compounds to aid in their addition into foods. This review discusses the structure and biological function of different nature-assembled carriers, preparation/isolation methods, some of the advantages and challenges in their use as bioactive compound delivery systems, and their behavior during digestion.

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Symposium review: Intravital imaging of the lactating mammary gland in live mice reveals novel aspects of milk-lipid secretion

Cited by 27 publications

References 125 publications

TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh

TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh

Organellar Contacts of Milk Lipid Droplets

Nature-Assembled Structures for Delivery of Bioactive Compounds and Their Potential in Functional Foods

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