Brian and hepatic Mt mRNA is reduced in response to mild energy restriction and n-3 polyunsaturated fatty acid deficiency in juvenile rats

Authors: Mehus, Aaron; Picklo, Matthew

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/13/2017
Publication Date: 10/18/2017
Publication URL: http://handle.nal.usda.gov/10113/6472331
Citation: Mehus, A.A., Picklo, M.J. 2017. Brian and hepatic Mt mRNA is reduced in response to mild energy restriction and n-3 polyunsaturated fatty acid deficiency in juvenile rats. Nutrients. 9(10):1145-1163. https://doi.org/10.3390/nu9101145.
DOI: https://doi.org/10.3390/nu9101145

Interpretive Summary: Undernutrition is a global problem that during childhood can significantly impede brain and body development. Infants and children are particularly susceptible to undernutrition because of the high energy demands required for normal growth. Dietary fat intake also is important to infants and children during development. It is well-established that dietary n-3 polyunsaturated fatty acids (n-3 PUFA) like docosahexaenoic acid (DHA) preferentially accumulate in the brain and are important for brain function. Metallothioneins (MTs) are protective proteins in the brain and liver that regulate cellular levels of metal ions. Reductions in MT expression are known to result in increased vulnerability to environmental stress and infection. In this work, we tested the hypothesis that undernutrition by energy restriction and dietary n-3 PUFA deficiency reduce MT expression in juvenile rats. Our data show that reduction in energy intake reduces MT expression in the cerebellum of young rats and that lack of dietary n-3 PUFA reduces MT expression in the liver. Reductions in MT levels may increase susceptibility to infection, heavy metal exposures, or other stressors that could potentially impede normal development.

Technical Abstract: Metallothioneins (MTs) perform several important regulatory and cytoprotective functions in tissues. Little data exist regarding the impact of undernutrition upon MT expression in growing animals. Since MT expression is altered by nutritional status, we tested the hypothesis that energy restriction (ER) with and without dietary n-3 deficiency reduces MT expression in juvenile rats. ER rats were individually pair-fed at 75% of the ad libitum (AL) intake of control rats provided diets consisting of either soybean oil (SO; a-linolenic acid (ALA) sufficient) or corn oil (CO; ALA deficient). Fatty acids (FA) and metal concentrations of liver and brain regions were analyzed. Tissue expression of MTs (Mt1-3) and modulators of MT expression including plasma corticosterone and triiodothyronine, glucocorticoid receptors (Nr3c1 and Nr3c2), and several mediators of thyroid hormone regulation (Dio1-3, Mct8, Oatp1c1, Thra, and Thrb) were measured. ER, but not n-3 deficiency or metal concentration, reduced Mt2 expression 50% in the cerebellum. In liver, reduction in dietary n-3 but not ER reduced Mt1, Mt2, and Thrb. ER elevated Nr3c1, Dio1, Thrb and reduced Thra in the liver. Given MTs role in cellular protection, further studies are needed to evaluate whether ER or n-3 deficiency may leave the juvenile brain and or liver more susceptible to endogenous or environmental stressors.