Abstract
Nonalcoholic fatty liver disease (NAFLD) has been a major cause of a chronic liver disease over recent decades and increasing worldwide in parallel with the remarkable growth of obesity. In the present study, we investigate the ameliorative effects of PCM, a combination of Diospyros kaki fruit and Citrus unshiu peel mixture, on high-fat diet- (HFD-) induced NAFLD and clarify the potential mechanisms. PCM in HFD-fed mice was orally administered at a dose of 50 or 100 mg/kg subsequently for 2 months. Thereafter, lipid metabolism parameters and fat synthesis-related genes in the mouse liver were evaluated. Subsequently, body weight changes, liver weight, serum liver function and lipid profiles, and liver pathology were examined, and the relative levels of fatty acid synthesis and β-oxidation gene expression were evaluated by western blot. Serum AST, ALT, and TG levels in the HFD control mice were significantly higher than those of normal mice. Compared with HFD control mice, PCM supplementation increased phosphorylation of AMP-activated protein kinase (AMPK). Peroxisome proliferator-activated receptor (PPAR) α was significantly increased by PCM administration. Continuously, the activation of PPARα significantly elevated carnitine palmitoyltransferase 1 (CPT-1), a key enzyme in fatty acid β-oxidation, and mitochondrial uncoupling protein 2 (UCP-2), thermogenic regulatory genes, in PCM-treated mice compared with those of HFD control mice. Moreover, PCM inhibits lipogenesis and cholesterol synthesis via suppression of sterol regulatory element binding protein-1 (SREBP-1) and SREBP-2 and its target genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Taken together, these effects were mediated through activation of AMPK. In the conclusion, PCM improved liver damage in HFD-fed mice and attenuated NAFLD by the activation of PPARα and the inhibition of SREBPs expression via AMPK-dependent pathways.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease and characterized by the accumulation of triglycerides in liver hepatocytes of patients without the excess consumption quantities of alcohol. e prevalence of NAFLD is constantly rising worldwide in parallel with overnutrition associated with high-fat and high-carbohydrate intake [1]
NAFLD patients are commonly accompanied with obesity, diabetes, and hyperlipidemia, but not all obese people develop into NAFLD, and the various factors may play the important role in the pathogenesis of NAFLD
Dietary acetic acid is metabolized to acetyl-CoA with the production of AMP. e AMP-activated protein kinase (AMPK), an energy sensor, is activated by increase in the cellular AMP:ATP ratio caused by multiple stresses and induces metabolic changes through the modulation of gene expressions concerned in metabolic regulation [7]
Summary
Nonalcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease and characterized by the accumulation of triglycerides in liver hepatocytes of patients without the excess consumption quantities of alcohol. e prevalence of NAFLD is constantly rising worldwide in parallel with overnutrition associated with high-fat and high-carbohydrate intake [1]. E prevalence of NAFLD is constantly rising worldwide in parallel with overnutrition associated with high-fat and high-carbohydrate intake [1]. Erefore, a lot of attention has been focused on natural products, which increase fat oxidation and decrease adipogenesis and regulate lipid metabolism effectively. AMPK maintains cellular energy homeostasis through the inhibition of fatty acid synthesis and the activation of fatty acid oxidation [8]. In this context, many researchers reported that these resulted from the inhibition of the cleavage and transcriptional activation of SREBP via direct phosphorylation of AMPK in the liver [6, 9]. Many researchers reported that these resulted from the inhibition of the cleavage and transcriptional activation of SREBP via direct phosphorylation of AMPK in the liver [6, 9]. us, AMPK has been recognized as a significant target for the management of obesity and hyperlipidemia
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