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Severe zinc deficiency is associated with an increased systemic inflammatory response and mortality after sepsis. However, the impact of mild zinc deficiency, which is more common in populations with chronic illnesses and sepsis, is unknown. In this study, we hypothesized that marginal dietary Zn deprivation (ZM) would amplify tissue inflammation and exacerbate the sepsis-induced decrease in muscle protein synthesis. Adult male C57BL/6 mice were fed a zinc-adequate (ZA) or ZM diet (30 or 10 mg Zn/kg, respectively) over 4 weeks, peritonitis was induced by cecal ligation and puncture (CLP), and mice were examined at either 24 h (acute) or 5 days (chronic) post-CLP. Acute sepsis decreased the in vivo rate of skeletal muscle protein synthesis and the phosphorylation of the mTOR substrate 4E-BP1. Acutely, sepsis increased TNF-α and IL-6 mRNA in muscle, and the increase in TNF-α was significantly greater in ZM mice. However, muscle protein synthesis and 4E-BP1 phosphorylation returned to baseline 5 days post-CLP in both ZA and ZM mice. Protein degradation via markers of the ubiquitin proteasome pathway was increased in acute sepsis, yet only MuRF1 mRNA was increased in chronic sepsis and ZM amplified this elevation. Our data suggest that mild zinc deficiency increases TNF-α in muscle acutely after sepsis but does not significantly modulate the rate of muscle protein synthesis. [ABSTRACT FROM AUTHOR]

Zinc (Zn) requirements are increased during lactation. Increased demand is partially met through increased Zn absorption from the diet. It is estimated that 60–80% of women of reproductive age are at risk for Zn deficiency due to low intake of bioavailable Zn and increased demands during pregnancy and lactation. How Zn is redistributed within the body to meet the demands of lactation, and how Zn deficiency affects this process, is not understood. Female C57bl/6J mice were fed a control (ZA; 30 mg Zn/kg) or a marginally Zn deficient (ZD; 15 mg Zn/kg) diet for 30 days prior to mating through mid-lactation and compared with nulliparous mice fed the same diets. While stomach and plasma Zn concentration increased during lactation in mice fed ZA, mice fed ZD had lower stomach Zn concentration and abrogated plasma Zn levels during lactation. Additionally, femur Zn decreased during lactation in mice fed ZA, while mice fed ZD did not experience this decrease. Furthermore, red blood cell, pancreas, muscle and mammary gland Zn concentration increased, and liver and adrenal gland Zn decreased during lactation, independent of diet, while kidney Zn concentration increased only in mice fed ZD. Finally, maternal Zn deficiency significantly increased the liver Zn concentration in offspring but decreased weight gain and survival. This study provides novel insight into how Zn is redistributed to meet the increased metabolic demands of lactation and how marginal Zn deficiency interferes with these homeostatic adjustments. [ABSTRACT FROM AUTHOR]

Background Mild dietary zinc (Zn) deficiency is widespread in human populations, but its influence on recovery after acute illness is poorly understood. In a mouse model of abdominal sepsis (cecal ligation puncture), systemic immune responses and liver metabolism were monitored in early (24 h) and late (5 d) phases, under control conditions and during mild dietary Zn restriction. Methods Mice were fed diets adequate or marginally deficient (ZM) in Zn (30 versus 10 mg zinc/kg diet) for 4 wk, before undergoing laparotomy alone (nonseptic control) or cecal ligation puncture (septic). Results Among nonseptic mice, the ZM state was not associated with differences in inflammation or metabolic responses. Among septic mice, mortality did not differ between the zinc adequate and ZM groups. In the early phase, the ZM state amplified increases in plasma interleukin (IL) 6, tumor necrosis factor alpha, and IL-10, while dampening the interferon gamma response. In the late phase, subtle but significant ZM-associated increases were observed in plasma IL-5 and interferon gamma levels and hepatic protein synthesis, the latter of which appeared to be mammalian target of rapamycin independent and was associated with increased hepatic tumor necrosis factor alpha messenger RNA content. Conclusions Without increasing mortality, the ZM state is associated with a more disordered acute systemic inflammatory response and persistence or enhancement of acute phase responses within the liver parenchyma. [ABSTRACT FROM AUTHOR]

Zinc (Zn) regulates numerous cellular functions. Zn deficiency is common in females; ∼80% of women and 40% of adolescent girls consume inadequate Zn. Zn deficiency enhances oxidative stress, inflammation and DNA damage. Oxidative stress and inflammation is associated with breast disease. We hypothesized that Zn deficiency increases oxidative stress in the mammary gland, altering the microenvironment and architecture. Zn accumulated in the mammary glands of Zn deficient mice and this was associated with macrophage infiltration, enhanced oxidative stress and over-expression of estrogen receptor α. Ductal and stromal hypercellularity was associated with aberrant collagen deposition and disorganized e-cadherin. Importantly, these microenvironmental alterations were associated with substantial impairments in ductal expansion and mammary gland development. This is the first study to show that marginal Zn deficiency creates a toxic microenvironment in the mammary gland impairing breast development. These changes are consistent with hallmarks of potential increased risk for breast disease and cancer. [ABSTRACT FROM AUTHOR]