Marginal Maternal Zinc Deficiency in Lactating Mice Reduces Secretory Capacity and Alters Milk Composition ,

Dempsey, Colleen; McCormick, Nicholas H.; Croxford, Thomas P.; Seo, Young Ah; Grider, Arthur; Kelleher, Shannon L.

doi:10.3945/jn.111.150623

Cited by 42 publications

(50 citation statements)

References 61 publications

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“…Collectively, the loss of ZnT2 resulted in mammary gland hypoplasia, the underlying cause of failed lactogenesis II where the mother is unable to produce an adequate milk volume (79). The etiology of breast hypoplasia is unknown, but our observations along with previous studies regarding zinc deficiency and the mammary gland (3)(4)(5) suggest that tight regulation of zinc metabolism plays an important role in regulating mammary gland biology.…”

Section: Discussionmentioning

confidence: 46%

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Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

Lee

Hennigar

Alam

et al. 2015

Journal of Biological Chemistry

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Background: ZnT2 is expressed in non-secreting and secreting mammary epithelium; however, the physiological role is not understood. Results: ZnT2-null mice have impaired mammary expansion and compromised mammary differentiation and milk secretion during lactation. Conclusion: ZnT2-mediated zinc transport is critical for mammary development and function during lactation. Significance: This study identifies novel consequences of ZnT2 function in the mammary gland.

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Section: Discussionmentioning

confidence: 46%

“…Collected milk samples (n ϭ 5 dams/genotype) were immediately used to measure the percentage of milk fat by creamatocrit as previously described (5). Frozen milk samples were thawed on ice and centrifuged at 2000 ϫ g for 15 min 4°C to skim.…”

Section: Methodsmentioning

confidence: 99%

Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

Lee

Hennigar

Alam

et al. 2015

Journal of Biological Chemistry

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“…The protein and lactose contents of the Spot14-null milk and the MMTV-Spot14 milk were not altered relative to control milk (data not shown). A weighsuckle-weigh approach was used to determine the amount of milk produced in a 2 h period ( 47 ). Milk production in the Spot14-null dams was equivalent to controls, suggesting milk synthesis and secretion is not obstructed ( Fig.…”

Section: Spot14-null Dams But Not Mmtv-spot14 Dams Produce Lipid-pomentioning

confidence: 99%

“…Weigh-suckle-weigh experiments were conducted according to Dempsey et al ( 47 ). Milk protein concentrations were determined using the Pierce 660 protein assay (Thermo Fisher Scientifi c).…”

Section: Milk Fat and Fatty Acid Composition Analysismentioning

confidence: 99%

Thyroid hormone responsive protein Spot14 enhances catalysis of fatty acid synthase in lactating mammary epithelium

Rudolph

Wellberg

Lewis

et al. 2014

Journal of Lipid Research

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This article is available online at http://www.jlr.orgMammalian cells manufacture fatty acids de novo using a distinct pathway to synthesize fatty acids from acetyl and malonyl esters of CoA catalyzed by the dimer of FASN (EC 2.3.1.85) ( 1 ). FASN is absolutely essential for production of de novo fatty acids in mammals ( 2 ). The biological requirement for FASN is highlighted by the fact that FASN is detected in most normal human tissues and that homozygous deletion of FASN in the mouse results in embryonic lethality ( 3, 4 ). The importance of the de novo pathway is underscored by the complex biological functions of its fatty acid products, including biosynthesis of phospholipids, energy storage via esterifi cation into triglycerides (TAGs), use as energy substrates for ␤ -oxidation, providing both endocrine and nuclear hormone signaling ligands, and for critical posttranslational modifi cations of proteins ( 5-12 ). Perhaps the most demanding setting for FASN catalysis is during lactation, when extremely high quantities of de novo fatty acids are transmitted to the offspring as substrate for the growth of the young ( 13-15 ).Regulation of the principle enzymes of de novo fatty acid synthesis, ATP citrate lyase (ACLY) (EC 2.3.3.8), acetyl-CoA carboxylase (ACC) (EC 6.4.1.2), and FASN, has been shown to occur at the level of enzyme gene expression ( 16 ), translation/degradation ( 17-19 ), phosphorylation ( 20-22 ), assembly into multimeric complexes ( 23-25 ), and allosteric activation/inhibition ( 18,23,26,27 ). Recently, evidence for the control of de novo fatty acid synthesis by small effector proteins has emerged. Thyroid hormone responsive protein "Spot 14" (THRSP) (Spot14, S14) and only family Abstract Thyroid hormone responsive protein Spot 14 has been consistently associated with de novo fatty acid synthesis activity in multiple tissues, including the lactating mammary gland, which synthesizes large quantities of medium chain fatty acids (MCFAs) exclusively via FASN. However, the molecular function of Spot14 remains undefi ned during lactation. Spot14-null mice produce milk defi cient in total triglyceride and de novo MCFA that does not sustain optimal neonatal growth. The lactation defect was rescued by provision of a high fat diet to the lactating dam. Transgenic mice overexpressing Spot14 in mammary epithelium produced total milk fat equivalent to controls, but with significantly greater MCFA. Spot14-null dams have no diminution of metabolic gene expression, enzyme protein levels, or intermediate metabolites that accounts for impaired de novo MCFA. When

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“…Zn concentrations of ZnDF and ZnSP diets were selected based on previous studies. [21][22][23][24][25] Non-pregnant mice were maintained under the same conditions as pregnant mice. All animal experiments were approved by the Animal Research Committee of Osaka Ohtani University in accordance with the Guidelines on Animal Experiments at Osaka Ohtani University and Japanese Government Animal Protection and Management Laws.…”

Section: Methodsmentioning

confidence: 99%

Effects of Zinc Deficiency and Supplementation on Leptin and Leptin Receptor Expression in Pregnant Mice

Ueda

Nakai

Konishi

et al. 2014

Biological & Pharmaceutical Bulletin

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Leptin is an adipose-derived hormone that primarily regulates energy balance in response to nutrition. Human placental cells produce leptin, whereas murine placental cells produce soluble leptin receptors (Ob-R). However, the roles of these proteins during pregnancy have not been elucidated completely. As an essential metal, zinc (Zn) is central to insulin biosynthesis and energy metabolism. In the present study, the effects of Zn deficiency and supplementation on maternal plasma leptin and soluble Ob-R regulation in pregnant mice placentas were examined using enzyme-linked immunosorbent assay, reverse transcriptionpolymerase chain reaction, and Western blotting. Nutritional Zn deficiency significantly reduced plasma insulin concentrations and fetal and placental weights in pregnant mice. Plasma leptin concentrations in pregnant mice also increased 20-to 40-fold compared with those in non-pregnant mice. Although dietary Zn deficiency and supplementation did not affect plasma leptin concentrations in non-pregnant mice, Zndeficient pregnant mice had significantly reduced plasma leptin concentrations and adipose leptin mRNA expression. In contrast, Zn-supplemented pregnant mice had increased plasma leptin concentrations without increased adipose leptin mRNA expression. Placental soluble Ob-R mRNA expression also decreased in Zndeficient mice and tended to increase in Zn-supplemented mice. These results indicate that Zn influences plasma leptin concentrations by modulating mRNA expression of soluble Ob-R in the placenta, and leptin in visceral fat during pregnancy. These data suggest that both adipose and placenta-derived leptin system are involved in the regulation of energy metabolism during fetal growth. Key words leptin; leptin receptor; dietary zinc; pregnancy; placentaLeptin is a 16-kDa protein hormone encoded by lep and is mainly produced in adipose tissues. Initial studies indicated that it regulates body weight by suppressing appetite and stimulating energy consumption via the hypothalamic leptin receptor (Ob-R).1,2) In addition to its known role in energy metabolism, pleiotropic effects of leptin have been identified, involving modulation of thermogenesis, homeostasis, hematopoiesis, angiogenesis, neuroendocrine, and immune functions. Moreover, leptin regulates ovarian function, oocyte maturation, and implantation.3,4) Recently, significantly elevated plasma leptin concentrations were found in pregnant women, with considerable leptin secretion from the placenta in comparison with that observed in non-pregnant women. 5)In the second and third trimesters, plasma leptin concentrations further increased in comparison with that observed in the first trimester and returned to normal after expulsion of placenta, suggesting that the placenta is the major source of leptin during pregnancy. 5) Leptin is not produced in mouse placentas, although plasma leptin concentrations are also elevated during pregnancy, and high placental production of soluble Ob-R has been demonstrated in mice. It was reported that secretions ...

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Marginal Maternal Zinc Deficiency in Lactating Mice Reduces Secretory Capacity and Alters Milk Composition ,

Cited by 42 publications

References 61 publications

Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

Thyroid hormone responsive protein Spot14 enhances catalysis of fatty acid synthase in lactating mammary epithelium

Effects of Zinc Deficiency and Supplementation on Leptin and Leptin Receptor Expression in Pregnant Mice

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