Association of Hypoadiponectinemia with Hypoglutathionemia in NAFLD Subjects with and without Type 2 Diabetes

Abstract

Abstract.Objective: The aim of this study is to measure the extent of oxidative stress and to see whether it has any correlation to changes in adiponectin levels in NAFLD subjects with and without Type 2 diabetes. Methods: Subjects recruited from the Chennai Urban Rural Epidemiology Study comprise of 1: Normal Glucose Tolerance (NGT) subjects without NAFLD; 2: NGT with NAFLD; 3: Type 2 Diabetic patients [T2DM] without NAFLD and 4: T2DM with NAFLD. Thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCO), glutathione and adiponectin levels were measured by standard methods. Ultrasound of the liver was used to diagnose NAFLD. Results: T2DM subjects with NAFLD had significantly (p < 0.001) higher levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCO) but lower (p < 0.001) GSH/GSSG ratio and adiponectin levels compared to other three groups. The association of hypoadiponectinemia with NAFLD/Type 2 diabetes was significant even after adjusting for age, gender and BMI, but lost when adjusted for parameters of oxidative stress. While palmitate significantly reduced GSH/GSSG ratio in hepatocytes, addition of exogenous recombinant adiponectin restored the GSH/GSSG ratio comparable to those of untreated cells. Conclusion:There exists an association of hypoglutathionemia and hypoadiponectinemia in subjects with NAFLD and/or T2DM. In addition to the known beneficial effects, out study also exposes the antioxidant nature of adiponectin.

Oxidative stress and inflammatory markers in relation to circulating levels of adiponectin

“…An inverse correlation between adiponectin and the ratio of GSSG/GSH was found in 12 obese psoriasis patients () and similarly adiponectin correlated positively with the GSG/GSSG ratio in 120 subjects with or without diabetes and with or without nonalcoholic fatty liver disease (). Further, adiponectin was shown to restore the GSH/GSSG ratio after it was reduced when treating HepG2 cells with palmitate (). We did not find a significant association with the GSH/GSSG ratio, but a strong association with the absolute levels of GSH and TGSH.…”

“…Some previous studies, mostly in smaller and/or selected study samples, have shown an association between adiponectin and pro‐ and anti‐oxidative markers (). The association between adiponectin and glutathione (GSH) remains to be fully elucidated, but an association between adiponectin and the ratio of oxidized and reduced GSH has been suggested (). An inverse correlation between adiponectin and measures of lipid peroxidation has been reported in some studies (), but not all ().…”

Estimation of adiponectin levels in diabetic, non-diabetic fatty liver diseases and healthy controls

“…This finding is in accordance with previous studies in both western and Asian populations. [14][15][16] Adiponectin concentrations are 20-60% lower in patients with NAFLD than in healthy persons. 17 The present study indicates that 80% of the DFL patients and 72% of subjects of NDFL group have BMI >25 kg/m 2 and 80% of subjects in the DFL group and 68% of the subjects in the NDFL group have a waist circumference that indicates central obesity as per Asian cut-offs.…”

Inflammatory Markers in Relation to Nonalcoholic Fatty Liver Disease in Urban South Indians

“…NAFLD was also shown to be associated with hypoglutathionemia and hypoadiponectinemia. 26 NAFLD and other insulin-resistant states are associated with activation of the innate immune system, resulting in chronic subclinical inflammation. 27 Some studies have documented a significant association between leukocyte count and the metabolic syndrome.…”