Abstract
Shenling Baizhu San (SLBZS), a famous traditional Chinese medicine, has been demonstrated to exert protective effects against non-alcoholic fatty liver disease (NAFLD), but its exact mechanisms have not been well understood. The aim of this study was to investigate the mechanisms underlying the protective effects of SLBZS in a rat model of NAFLD using lipidomics and to evaluate the role of Sirtuin 1 (SIRT1) in the mechanism of SLBZS against NAFLD. The rat model of NAFLD was induced by high-fat feeding. An ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based untargeted lipidomics approach was applied to analyze hepatic lipid alterations, and the SIRT1-selective inhibitor EX 527 was used to inhibit SIRT expression in the liver. The results of body and biochemical parameters, as well as histological changes, indicated that SLBZS administration exerted protective effects against NAFLD. Lipidomic analysis showed that 30 lipid species were effectively regulated by SLBZS administration in rats fed a high-fat diet. Pathway analysis indicated that glycerophospholipid metabolism and glycerolipid metabolism were potential target pathways closely involved in the mechanism of SLBZS against NAFLD. Moreover, the beneficial effects of SLBZS on hepatic steatosis, some biochemical parameters and hepatic lipid species were partly diminished by SIRT1 inhibition. In conclusion, our results suggested that SLBZS administration could effectively alter some hepatic lipid species in rats fed a high-fat diet, which was mainly associated with the regulation of glycerophospholipid and glycerolipid metabolism. Furthermore, the beneficial effects of SLBZS on hepatic lipid metabolism may be at least partly attributed to SIRT1 activation in the liver.
Highlights
Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide [1], is characterized by excessive fat accumulation in the liver without other causes, such as significant alcohol consumption or the use of steatogenic medication [2]
We attempted to investigate the mechanisms underlying the protective effects of Shenling Baizhu San (SLBZS) in a rat model of NAFLD, with a focus on hepatic lipid metabolism, using ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based untargeted lipidomics
An untargeted lipidomics approach was successfully employed to investigate the protective effects of SLBZS against NAFLD in rats
Summary
Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide [1], is characterized by excessive fat accumulation in the liver without other causes, such as significant alcohol consumption or the use of steatogenic medication [2]. NAFLD is considered to be closely related to metabolic syndrome, which is characterized by the presence of obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar [5]. Lipids are a unique group of compounds involved in a large number of structural and biological functions in cells to maintain homeostasis [7,8]. Dysregulation of lipid metabolism has been demonstrated to be closely linked with various common metabolic diseases, such as NAFLD [9], obesity [10], and type 2 diabetes mellitus [11]. Lipidomics, a branch of the field of metabolomics, is a biomedical systems-level analysis aiming to characterize lipid species and investigate the complex biological metabolic networks of lipids in biological systems [12]
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