Magnesium isoglycyrrhizinate prevents the nonalcoholic hepatic steatosis via regulating energy homeostasis.

Wenjiao Jiang,Kun Hao,Shiyu Xu,Huijie Guo,Guangji Wang,Li Lu,Jie Liu

doi:10.1111/jcmm.15230

Abstract

Non‐alcoholic fatty liver disease is a public health problem worldwide associated with high morbidity and hepatic steatosis, but no effective therapeutic interventions. Magnesium isoglycyrrhizinate (MGIG), a derivative of an active component of Glycyrrhiza glabra, is widely used for the treatment of inflammatory liver diseases due to its potent anti‐inflammatory and hepatoprotective activities. Hence, this study aimed to study the effects of MGIG on hepatic steatosis in mice fed a high‐fat diet (HFD). Oil Red O staining and transmission electron microscopy revealed a decrease in lipid accumulation in the liver after MGIG treatment along with improved mitochondrial ultramicrostructures. Metabonomic analysis demonstrated that MGIG intervention increased glutamate utilization in mitochondria by promoting the uptake of glutamate into the tricarboxylic acid (TCA) cycle. The NAD+/NADH ratio and the expression of other lipid‐metabolism‐related genes were increased in MGIG‐treated livers. Transcriptome sequencing showed that the expression of TLR4, an isoform of the innate immunity Toll‐like receptors (TLRs), was significantly decreased after MGIG treatment, suggesting a link between the anti‐inflammatory effects of MGIG and its suppression of lipidation. Our results reveal the potent effects of MGIG on lipid metabolism and suggest that hepatic TLR4 might be a crucial therapeutic target to regulate energy homeostasis in hepatic steatosis.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide that is linked to high morbidity.[1]
The expression of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN) are influenced by SREBP-1c, which is activated in response to insulin levels
Mature SREBP-1c functions as an activated transcription factor regulating the expression of enzymes involved in hepatic lipogenesis such as FASN and ACC1.25 A significant increase in hepatic levels of SREBP-1c and its target lipid synthesis enzymes, FASN and ACC, is observed in NAFLD patients as well as in high-fat diet (HFD)-fed rodents, which is followed by a large amount of TG deposition.[26,27]

Summary

| INTRODUCTION

Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide that is linked to high morbidity.[1]. A high-fat diet (HFD) and inflammation serve as inducers to contribute to the progression of NAFLD.[4]. The HFD method is used to induce liver steatosis. AMPK-mediated energy metabolism promotes fatty acid oxidation in HFD-fed mice.[10]. Fatty liver disease can be attributed to a variety of major lipogenesis-controlling factors, such as sterol regulatory element-binding protein-1c (SREBP-1c). MGIG has been widely used for the treatment of inflammatory liver diseases due to its potent anti-inflammatory and hepatoprotective activities.[12-14]. There are no reports on the in vivo effects of MGIG on non-alcoholic hepatic steatosis. The present study aimed to investigate the pharmacological effects of MGIG on HFD-induced hepatic steatosis in mice and explore the underlying mechanism

| MATERIALS AND METHODS

Findings

| DISCUSSION