Abstract

Non-alcoholic fatty liver disease (NAFLD) is currently estimated as the most prevalent chronic liver disease in all age groups. An increasing body of evidence obtained in experimental and clinical data indicates that oxidative stress is the most important pathogenic factor in the development of NAFLD. The study aimed to investigate the impact of α-lipoic acid (LA), widely used as an antioxidant, on the effects of a hypercaloric choline-deficient diet. Male Wistar rats were divided into three groups: control diet (C); hypercaloric choline-deficient diet (HCCD), and hypercaloric choline-deficient diet with α-lipoic acid (HCCD+LA). Supplementation of HCCD with LA for eight weeks led to a decrease in visceral adipose tissue/body weight ratio, the activity of liver glutathione peroxidase and paraoxonase-1, plasma, and liver total antioxidant activity, as well as an increase in liver/body weight ratio, liver total lipid and triglyceride content, and liver transaminase activities compared to the HCCD group without LA. In conclusion, our study shows that α-lipoic acid detains obesity development but exacerbates the severity of diet-induced oxidative stress and lipid accumulation in the liver of male Wistar rats fed a hypercaloric choline-deficient diet.

Highlights

  • Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and type 2 diabetes, and is recognized as the most prevalent chronic liver disease in all age groups

  • Animals were divided into three groups: control group of rats fed a control diet (C); rats fed a hypercaloric choline-deficient diet (HCCD); rats fed a hypercaloric choline-deficient diet supplemented with α-lipoic acid (HCCD+LA; consumed average daily dose of LA-61 mg/kg body weight)

  • The results obtained in our work showed that feeding of rats with HCCD for eight weeks leads to an increase in the final body weight and weight gain as a result of a higher calorie intake and an increase in feed efficiency

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Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and type 2 diabetes, and is recognized as the most prevalent chronic liver disease in all age groups. NAFLD is accompanied by an increase in the CYP2E1 gene and protein expression, the accumulation of lipid peroxides in the liver [11]. The results of several clinical and experimental studies indicate a direct relationship between the suppression of antioxidant enzyme activities and the severity of NAFLD [12,13,14,15]. It was experimentally shown that the activation of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), the main regulator of the expression of antioxidant enzyme genes [16], leads to suppression of oxidative stress and a decrease in liver inflammation and fibrosis [17]. The study aimed to investigate the impact of α-lipoic acid (LA), which is widely used as an antioxidant [20], on the effects of hypercaloric choline-deficient (HCCD) diet in rats

Experimental Protocol
Metabolic Measurements
Liver Lipids Content
Glutathione Content
CYP2E1 Activity
Antioxidant Enzyme Activities
Histopathological Examination
Statistical Analysis
Liver Lipid Content
Metabolic Parameters
Oxidative Stress Markers
Findings
Discussion
Full Text
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