Vanadium(IV)-Chlorodipicolinate Protects against Hepatic Steatosis by Ameliorating Lipid Peroxidation, Endoplasmic Reticulum Stress, and Inflammation

Abstract

Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. The aim of this study is to investigate the protective effects and the underlying mechanisms of vanadium(IV)-chlorodipicolinate ([VIVO(dipic-Cl)(H2O)2, VOdipic-Cl]) in a mouse model of NAFLD induced by a high-fat diet (HFD). VOdipic-Cl (10 mg/kg/day body weight) treatment for 4 weeks significantly controlled body weight gain, and effectively reduced the increase in serum and hepatic triglyceride (TG) and total cholesterol (TC) levels, mitigated pathological injury, decreased malondialdehyde (MDA) level, and inhibited endoplasmic reticulum (ER) stress and inflammatory response in the livers of C57BL/6 obese mice. Moreover, RNA-sequencing analysis revealed distinct transcriptional profiles with differentially expressed genes (DEGs) in livers. We found that VOdipic-Cl effectively down-regulated genes related to lipid synthesis and up-regulated genes related to fatty acid transport and lipolysis, and down-regulated the expression of genes related to ER stress and immune response in the livers of obese mice. In conclusion, VOdipic-Cl effectively prevented hepatic steatosis by controlling body weight, mitigating oxidative stress, and regulating the expression of genes related to lipid metabolism, ER stress and immune response, which provides new insights into the molecular mechanism of the protective effect of VOdipic-Cl against hepatic steatosis.

Vanadium Complexes with Thioanilidine Derivatives of Aminoacids: Inhibition of Human Phosphatases and Cell-Type Specificity in Various Models of Metabolic Disturbances

“…An analogous effect for this complex was also observed in liver tissue from mice fed a high-fat diet [108]. Most of few studies on the effect of vanadium complexes on liver lipid disturbances used in vivo models and demonstrated the effectiveness against the mechanisms responsible for fatty liver [109,110].…”

Vanadium Complexes with Thioanilide Derivatives of Amino Acids: Inhibition of Human Phosphatases and Specificity in Various Cell Models of Metabolic Disturbances

“…An analogous effect for this complex was also observed in liver tissue from mice fed a high-fat diet [ 108 ]. Most of the few studies on the effect of vanadium complexes on liver lipid disturbances used in vivo models and demonstrated effectiveness against the mechanisms responsible for fatty liver [ 109 , 110 ].…”

“…On the other hand, the effects of the presence of halogens in the aromatic ring may not be unambiguous. Vanadium (IV)-chlorodipicolinate with a chlorine ligand at position 4 in the pyridine ring of dipicolinic acid showed beneficial effects in a mouse model of non-alcoholic fatty liver disease (NAFLD), effectively preventing hepatic steatosis and also mitigating oxidative stress and endoplasmic reticulum (ER) stress [ 109 ].…”

Vanadium, cobalt, zinc, and rubidium are associated with markers of inflammation and oxidative stress in a Greek population with obesity

“…Additionally, decreased body weight gain, lipids, and glucose levels as well as a suppression of preadipocyte differentiation and adipogenesis were observed in high-fat diet (HFD) mice given Jeju ground water containing V components compared to control mice (29). In a different study, a 4-week V supplementation reduced malondialdehyde (MDA) and inhibited endoplasmic reticulum stress and inflammatory response in addition to controlling body weight gain in HFD mice (30). In the majority of diabetes-induced animal studies, V administration was able to regulate oxidative stress biomarkers by restoring enzyme production at normal levels, such as raising catalase or glutathione peroxidase (31).…”