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Experimental Biology and Medicine 231:1542-1547 (2006)
© 2006 Society for Experimental Biology and Medicine

5TH INTERNATIONAL CONFERENCE ON METALLOTHIONEIN SYMPOSIUM PAPERS

Hepatic Responses to Dietary Stress in Zinc- and Metallothionein-Deficient Mice

John H. Beattie*,1, Margaret-Jane Gordon*, Martin D. Reid{dagger}, Garry J. Rucklidge{dagger}, Chong-Suk Kwon{ddagger} and In-Sook Kwun{ddagger}

* Division of Vascular Health and {dagger} Analytical Facility, Rowett Research Institute, Bucksburn, Aberdeen AB22 8WR, United Kingdom; and {ddagger} Department of Food Science and Nutrition, Andong National University, Andong, Kyungpook 760-749, South Korea

To whom requests for reprints should be addressed at 1 Division of Vascular Health, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, Scotland, UK. E-mail: J.Beattie{at}rowett.ac.uk

Abstract

Metallothionein (MT) and zinc are both reported to be protective against oxidative and inflammatory stress and may also influence energy metabolism. The role of MT in regulating intracellular labile zinc, thus influencing zinc (Zn)-modulated protein activity, may be a key factor in the response to stress and other metabolic challenges. The objective of this study was to investigate the influence of dietary zinc intake and MT on hepatic responses to a pro-oxidant stress and energy challenge in the form of a high dietary intake of linoleic acid, an omega-6 polyunsaturated fatty acid. Male MT-null (KO) and wild-type (WT) mice, aged 16 weeks, were given semisynthetic diets containing 16% fat and either 5 (marginally zinc-deficient [ZD]) or 35 (zinc-adequate [ZA]) mg Zn/kg. For comparison, separate groups of KO and WT mice were given a rodent chow diet containing 3.36% fat and 86.6 mg Zn/kg. After 4 months on these diets, the body weights of all mice were equal, but liver size, weight, and lipid content were much greater in the animals that consumed semisynthetic diets compared to the chow diet. The increase in liver size was significantly lower in ZA but not ZD KO mice, compared with WT mice. Principally, MT appears to affect the diet-induced increase in liver tissue but it also influences the concentration of hepatic lipid. Plasma levels of C-reactive protein (CRP), a marker of inflammation, were increased by zinc deficiency in WT mice, suggesting that marginal zinc deficiency is proinflammatory. CRP was unaffected by zinc deficiency in KO mice, indicating a role for MT in modulating the influence of zinc. Neither zinc nor MT deficiency affects the level of soluble liver proteins, as determined using two-dimensional (2D) gel proteomics. This study highlights the close association between zinc and MT in the manifestation of stress responses.

Key Words: zinc deficiency • metallothionein-null mice • linoleic acid • hepatic lipids • C-reactive protein • proteomics






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