Nicotinamide prevents sweet beverage-induced hepatic steatosis in rats by regulating the G6PD, NADPH/NADP+ and GSH/GSSG ratios and reducing oxidative and inflammatory stress.

Abstract:

:The disruption of redox state homeostasis, the overexpression of lipogenic transcription factors and enzymes, and the increase in lipogenic precursors induced by sweetened beverages are determinants of the development of nonalcoholic fatty liver disease. This study evaluated the action of nicotinamide (NAM) on the expression of glucose-6-phosphate dehydrogenase (G6PD) and redox, oxidative, and inflammatory states in a model of nonalcoholic hepatic steatosis induced by high and chronic consumption of carbohydrates. Male rats were provided drinking water with 30% glucose or fructose ad libitum for 12 weeks. Additionally, 30 days after the beginning of carbohydrate administration, some rats were simultaneously provided water with 0.06% or 0.12% NAM for 5h daily over the next 8 weeks. Biochemical profiles and expression levels of G6PD, tumor necrosis factor α (TNFα), and NADPH oxidase 4 (NOX4) were evaluated together with glutathione/glutathione disulfide (GSH/GSSG) and reduced nicotinamide adenine dinucleotide (phosphate)/nicotinamide adenine dinucleotide (phosphate) [NAD(P)H/NAD(P)] ratios and thiobarbituric acid reactive substances (TBARS). The results showed that hepatic steatosis induced by the chronic consumption of glucose or fructose was associated with body weight gain and increased levels of serum glucose, insulin, triacylglycerols, free fatty acids, transaminases, and TBARS. In the liver, the expression and activity of G6PD increased along with the GSSG, TBARS, and TG concentrations. These alterations were reduced by NAM treatment through the attenuation of increases in G6PD expression and activity and in the NADPH/NADP+ ratio, thereby slowing liver steatosis. NAM prevents redox, oxidative, and inflammatory alterations induced by high carbohydrate consumption.

journal_name

Eur J Pharmacol

authors

Mejía SÁ,Gutman LAB,Camarillo CO,Navarro RM,Becerra MCS,Santana LD,Cruz M,Pérez EH,Flores MD

doi

10.1016/j.ejphar.2017.10.048

subject

Has Abstract

pub_date

2018-01-05 00:00:00

pages

499-507

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(17)30696-9

journal_volume

818

pub_type

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