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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #262029
Title: Cellular methylation regulates hepatocyte expression of selenoprotein P and gluconeogenic enzymes

Author
item Jackson, Matthew
item Combs, Gerald

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 11/12/2010
Publication Date: 3/17/2011
Citation: Jackson, M.I., Combs, G.F. 2011. Cellular methylation regulates hepatocyte expression of selenoprotein P and gluconeogenic enzymes. Federation of American Societies for Experimental Biology Conference. 25:100.3.

Interpretive Summary:

Technical Abstract: S-adenosylmethionine (SAM) is a methyl donor whose levels are altered in disease, relative to its product, SAH. SAM is also required for metabolism of the nutrient Se. We previously found a positive correlation between Se and Vitamin B12/folic acid but a negative correlation between Se and homocysteine, indicating positive methylation status might facilitate Se metabolism. We also found levels of a selenoprotein, SEPP1, varied by BMI in overweight/obese human subjects. Obesity associates with fatty liver disease accompanied by altered hepatic methylation capacity and decreased levels of plasma indicators of methylation status. To test whether decreased methylation disrupts Se metabolism, we treated human hepatocytes with an inhibitor of transmethylation (adensylhomocysteine hydrolase). After treatment, the SAM/SAH ratio and SEPP1 protein/mRNA were all decreased. The inhibition of SEPP1 expression appears to be transcriptional, not due to decreased mRNA stability or translation. Additionally, glucocorticoid induced upregulation of SEPP1 synthesis was blocked by inhibition of methylation. Showing the generality of our observations, both basal and glucocorticoid-induced gluconeogenic enzyme expression was also decreased by SEPP1. In summary, we show that hepatocellular SAM-dependent methylation serves as a regulatory mechanism for both Se homeostasis and gluconeogeneic enzyme expression.