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Nicotinamide supplementation induces detrimental metabolic and epigenetic changes in developing rats

  • Da Li (a1) (a2), Yan-Jie Tian (a1), Jing Guo (a3), Wu-Ping Sun (a1), Yong-Zhi Lun (a1), Ming Guo (a3), Ning Luo (a1), Yu Cao (a2), Ji-Min Cao (a4), Xiao-Jie Gong (a1) and Shi-Sheng Zhou (a1)...

Abstract

Ecological evidence suggests that niacin (nicotinamide and nicotinic acid) fortification may be involved in the increased prevalence of obesity and type 2 diabetes, both of which are associated with insulin resistance and epigenetic changes. The purpose of the present study was to investigate nicotinamide-induced metabolic changes and their relationship with possible epigenetic changes. Male rats (5 weeks old) were fed with a basal diet (control group) or diets supplemented with 1 or 4 g/kg of nicotinamide for 8 weeks. Low-dose nicotinamide exposure increased weight gain, but high-dose one did not. The nicotinamide-treated rats had higher hepatic and renal levels of 8-hydroxy-2′-deoxyguanosine, a marker of DNA damage, and impaired glucose tolerance and insulin sensitivity when compared with the control rats. Nicotinamide supplementation increased the plasma levels of nicotinamide, N1-methylnicotinamide and choline and decreased the levels of betaine, which is associated with a decrease in global hepatic DNA methylation and uracil content in DNA. Nicotinamide had gene-specific effects on the methylation of CpG sites within the promoters and the expression of hepatic genes tested that are responsible for methyl transfer reactions (nicotinamide N-methyltransferase and DNA methyltransferase 1), for homocysteine metabolism (betaine–homocysteine S-methyltransferase, methionine synthase and cystathionine β-synthase) and for oxidative defence (catalase and tumour protein p53). It is concluded that nicotinamide-induced oxidative tissue injury, insulin resistance and disturbed methyl metabolism can lead to epigenetic changes. The present study suggests that long-term high nicotinamide intake (e.g. induced by niacin fortification) may be a risk factor for methylation- and insulin resistance-related metabolic abnormalities.

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Corresponding author

*Corresponding authors:S.-S. Zhou, ; fax +86 411 87402053, email zhouss@ymail.com; X.-J. Gong, email gxjsss@tom.com

References

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Nicotinamide supplementation induces detrimental metabolic and epigenetic changes in developing rats

  • Da Li (a1) (a2), Yan-Jie Tian (a1), Jing Guo (a3), Wu-Ping Sun (a1), Yong-Zhi Lun (a1), Ming Guo (a3), Ning Luo (a1), Yu Cao (a2), Ji-Min Cao (a4), Xiao-Jie Gong (a1) and Shi-Sheng Zhou (a1)...

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