Organellar Contacts of Milk Lipid Droplets

Monks, Jenifer; Ladinsky, Mark S.; McManaman, James L.

doi:10.1177/2515256419897226

Cited by 21 publications

(22 citation statements)

References 77 publications

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“…A distinctive feature of apocrine LD secretion by sMEC is the formation of stable, electron-dense 10-20 nm contacts between the LD and the apical plasma membrane (APM) (Wooding 1971) that induce alterations in the plasma membrane structure and spatial remodeling of integral membrane proteins and the glycocalyx (Peixoto de Menezes and Pinto da Silva 1978; Mather and Keenan 1998;Monks, et al, 2016), which are proposed to facilitate the apocrine secretion process (Vorbach, et al, 2002;Ogg, et al, 2004;Monks, et al, 2016). However, significant gaps remain in our understanding of the molecular and structural features that define LD-APM contacts, the mechanisms governing their formation and stabilization, and the functional relationships between membrane contact, envelopment, and secretion of LD (Monks, et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Perilipin-2 promotes lipid droplet-plasma membrane interactions that facilitate apocrine lipid secretion in secretory epithelial cells of the mouse mammary gland

Monks

Orlicky

Libby

et al. 2022

Front. Cell Dev. Biol.

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Secretory epithelial cells (sMEC) in mammary glands of lactating animals secrete lipids by a novel apocrine mechanism in which cytoplasmic lipid droplets (LD) contact and are enveloped by elements of the apical plasma membrane (APM) before being released into the lumen of the gland as membrane bound structures. The molecular properties of LD-APM contacts and the mechanisms regulating LD membrane envelopment and secretion are not fully understood. Perilipin-2 (Plin2) is a constitutive LD protein that has been proposed to tether LD to the APM through formation of a complex with the transmembrane protein, butyrophilin1a1 (BTN) and the redox enzyme, xanthine oxidoreductase (XOR). Using mice lacking Plin2 and physiological inhibition of apocrine lipid secretion, we demonstrate that LD-APM contact and envelopment are mechanistically distinct steps that they are differentially regulated by Plin2 and independent of LD secretion. We find that Plin2 is not required for formation of LD-APM contacts. However, it increases the percentage of LD that contact the APM and mediates enlargement of the LD-APM contact zone as LD undergo membrane envelopment. The effects of Plin2 LD-APM interactions are associated with increased abundances of BTN, XOR and Cidea, which are implicated as mediators of LD-APM contact formation, on membranes surrounding secreted LD, and with promotion of glycocalyx remodeling at LD-APM contact sites. We propose that Plin2 does not directly mediate contact between LD and the APM but acts by enhancing molecular interactions that stabilize LD-APM contacts and govern membrane envelopment of LD during apocrine lipid secretion. Plin2 does not appear to significantly affect the lipid content of milk in fully lactating animals, but it does increase lipid secretion at the onset of lactation in primaparous dams, which suggest a role in facilitating apocrine lipid secretion in sMEC during their initial transition to a secretory phenotype.

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Section: Introductionmentioning

confidence: 99%

Perilipin-2 promotes lipid droplet-plasma membrane interactions that facilitate apocrine lipid secretion in secretory epithelial cells of the mouse mammary gland

Monks

Orlicky

Libby

et al. 2022

Front. Cell Dev. Biol.

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“…Hybrid B. papyrifera flavone may have a similar effect, which can promote the mutual conversion of nutrients and increase the synthesis of milk fat. Cytoplasmic lipid droplet's is the direct precursors of milk lipids and are the storage place for newly formed lipids and other neutral lipids ( 50 ). The epithelial cells that secrete milk in the mammary gland have the function of synthesizing and secreting large amounts of neutral lipids, which are the main macronutrients in most mammalian milk.…”

Section: Discussionmentioning

confidence: 99%

Hybrid Broussonetia papyrifera Fermented Feed Can Play a Role Through Flavonoid Extracts to Increase Milk Production and Milk Fatty Acid Synthesis in Dairy Goats

Zhao

Dong-liang

et al. 2022

Front. Vet. Sci.

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In order to explore the effect of hybrid Broussonetia papyrifera fermented feed on milk production and milk quality of dairy goats, and to compare with alfalfa hay, three dairy goat diets were designed based on the principle of equal energy and equal protein. The goats in the control group were fed a basic TMR diet (CG group), and the other two groups were supplemented with 10% alfalfa hay (AH group) and 10% hybrid B. papyrifera fermented feed (BP group). The results showed that the dry matter intake and milk production of BP group increased significantly. The total amount of amino acids and the content of each amino acid in the milk of AH group and BP group were lower than those of CG group. The content of saturated fatty acids in the milk of BP group decreased while the content of unsaturated fatty acids increased. The contents of prolactin, estrogen and progesterone in BP goat serum were generally higher than those of AH goat and CG goat. Subsequently, this study separated and cultured mammary epithelial cells from breast tissue, and added flavone extracted from the leaves of hybrid B. papyrifera and alfalfa to their culture medium for comparison, which is one of their important bioactive components. The results showed that low-dose alfalfa flavone (AH) and hybrid B. papyrifera flavone (BP) can increase cell viability. They also can increase the accumulation of intracellular triglyceride and the formation of lipid droplets. Both AH flavone and BP flavone significantly up-regulated the expression of genes related to milk fat synthesis, including genes related to fatty acid de novo synthesis (ACACA, FASN, and SCD1), long-chain fatty acid activation and transport related genes (ACSL1), and genes related to transcription regulation (SREBP1). The three genes related to triglyceride synthesis (DGAT1, DGAT2, and GPAM) were all significantly increased by BP flavone. Both AH flavone and BP flavone significantly increased the protein expression of progesterone receptor and estrogen receptor in mammary epithelial cells but had no effect on prolactin receptor.

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“…The TAG is synthesized in or on the surfaces of rough endoplasmic reticulum membranes and is released into the cytoplasm as microlipid droplets with a surface coat of protein and polar lipid (Mather and Keenan, 1998). Then, the microlipid droplets in mammary epithelial cells fuse with each other to form larger cytoplasmic lipid droplets (Monks et al, 2020). The lipid droplet size affects the physiochemical characteristics of dairy products as well as the aggregation and coalescence properties of milk (O'Mahony et al, 2005;Couvreur and Hurtaud, 2017).…”

Section: Discussionmentioning

confidence: 99%

Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) regulates acetate- and β-hydroxybutyrate-induced milk fat synthesis by increasing FASN expression in mammary epithelial cells of dairy cows

Meng

Wang

et al. 2021

Journal of Dairy Science

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Increasing acetate and β-hydroxybutyrate (BHB) supply to lactating cows will increase milk fat synthesis. However, the underlying molecular mechanism remains largely unknown. Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) is a lipid dropletassociated protein that promotes intracellular triacylglycerol accumulation. In the present study, using gene overexpression and knockdown, we detected the contributions of CIDEC on milk fat synthesis in mammary epithelial cells of dairy cows in the presence of acetate and BHB. The results showed that knockdown of CIDEC decreased fatty acid synthase (FASN) expression and intracellular triacylglycerol content, whereas overexpression of CIDEC had the opposite effect. The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) regulates cell growth and differentiation in the mammary gland. We demonstrated that the FASN promoter had a canonical C/EBPβ binding sequence. CEBPB overexpression upregulated FASN expression and milk fat synthesis, whereas CEBPB knockdown had the opposite effect. Moreover, knockdown of CEBPB attenuated the promoting effects of CIDEC on acetateand BHB-induced FASN transcription. Taken together, our data showed that acetate and BHB induced FASN expression in mammary epithelial cells of dairy cows in a CIDEC-C/EBPβ-dependent manner, which provides new insights into the understanding of the molecular events involved in milk fat synthesis.

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Organellar Contacts of Milk Lipid Droplets

Cited by 21 publications

References 77 publications

Perilipin-2 promotes lipid droplet-plasma membrane interactions that facilitate apocrine lipid secretion in secretory epithelial cells of the mouse mammary gland

Perilipin-2 promotes lipid droplet-plasma membrane interactions that facilitate apocrine lipid secretion in secretory epithelial cells of the mouse mammary gland

Hybrid Broussonetia papyrifera Fermented Feed Can Play a Role Through Flavonoid Extracts to Increase Milk Production and Milk Fatty Acid Synthesis in Dairy Goats

Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) regulates acetate- and β-hydroxybutyrate-induced milk fat synthesis by increasing FASN expression in mammary epithelial cells of dairy cows

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