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

被引：39

作者：

Angeles Mejia, Selene ^{[1
,2
,3
]}

Baiza Gutman, Luis Arturo ^{[4
]}

Ortega Camarillo, Clara ^{[2
]}

Medina Navarro, Rafael ^{[5
]}

Sanchez Becerra, Martha Catalina ^{[2
]}

Damasio Santana, Leticia ^{[6
]}

Cruz, Miguel ^{[2
]}

Hernandez Perez, Elizabeth ^{[3
]}

Diaz Flores, Margarita ^{[2
]}

机构：

[1] Univ Autonoma Metropolitana, Unidad Iztapalapa, Div Ciencias Biol & Salud, Ciudad De Mexico, Mexico

[2] Hosp Especialidades Bernardo Sepulveda, Ctr Med Nacl Siglo 21, Inst Mexicano Seguro Social, Unidad Invest Med Bioquim, Av Cuauhtemoc 330, Ciudad De Mexico 06725, Mexico

[3] Univ Autonoma Metropolitana, Unidad Iztapalapa, Dept Ciencias Salud, Ciudad De Mexico, Mexico

[4] Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Unidad Morfol & Func, Lab Biol Desarrollo, Estado De Mexico, Mexico

[5] Ctr Invest Biomed Michoacan CIBIMI IMSS, Dept Metab Expt, Morelia, Michoacan, Mexico

[6] Hosp Especialidades Bernardo Sepulveda, Ctr Med Nacl Siglo 21, Inst Mexicano Seguro Social, Unidad Invest Med Enfermedades Endocrinas, Ciudad De Mexico, Mexico

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2018年 / 818卷

关键词：

G6PD; NADPH/NADP(+); GSH/GSSG; Nicotinamide; Nonalcoholic fatty liver; NONALCOHOLIC FATTY LIVER; HIGH-DOSE NICOTINAMIDE; INSULIN-RESISTANCE; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; DISEASE; DIET; SUPPLEMENTATION; STEATOHEPATITIS; OBESITY; MICE;

D O I：

10.1016/j.ejphar.2017.10.048

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 5 h daily over the next 8 weeks. Biochemical profiles and expression levels of G6PD, tumor necrosis factor alpha (TNF alpha), 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.

引用

页码：499 / 507

页数：9

共 53 条

[1] Hepatocyte Nicotinamide Adenine Dinucleotide Phosphate Reduced Oxidase 4 Regulates Stress Signaling, Fibrosis, and Insulin Sensitivity During Development of Steatohepatitis in Mice [J].