Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, encompassing a range of conditions caused by lipid deposition within liver cells, and is also associated with obesity and metabolic diseases. Here, we investigated the protective effects of diphlorethohydroxycarmalol (DPHC), which is a polyphenol isolated from an edible seaweed, Ishige okamurae, on palmitate-induced lipotoxicity in the liver. DPHC treatment repressed palmitate-induced cytotoxicity, triglyceride content, and lipid accumulation. DPHC prevented palmitate-induced mRNA and protein expression of SREBP (sterol regulatory element-binding protein) 1, C/EBP (CCAAT-enhancer-binding protein) α, ChREBP (carbohydrate-responsive element-binding protein), and FAS (fatty acid synthase). In addition, palmitate treatment reduced the expression levels of phosphorylated AMP-activated protein kinase (AMPK) and sirtuin (SIRT)1 proteins, and DPHC treatment rescued this reduction. Moreover, DPHC protected palmitate-induced liver toxicity and lipogenesis, as well as inflammation, and enhanced AMPK and SIRT1 signaling in zebrafish. These results suggest that DPHC possesses protective effects against palmitate-induced toxicity in the liver by preventing lipogenesis and inflammation. DPHC could be used as a potential therapeutic or preventive agent for fatty liver diseases.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver diseases worldwide and is characterized by fat deposition in the hepatocytes of patients without history of excessive alcohol consumption
Damage assay was performed, which demonstrated that palmitate induced cellular damage and was protected against by pretreatment of DPHC (Figure 1c), indicating that DPHC possesses a protective effect against palmitate-induced toxicity in HepG2 cells
We found that the mRNA expression of sterol regulatory element-binding protein (SREBP)1c, CCAAT-enhancer-binding protein (C/EBP)α, carbohydrate-responsive element-binding protein (ChREBP), and fatty acid synthase (FAS) were increased by palmitate exposure, whereas increases in levels of these mRNAs were suppressed, similar to control levels (Figure 3a–d)
Summary
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver diseases worldwide and is characterized by fat deposition in the hepatocytes of patients without history of excessive alcohol consumption. NAFLD is associated with metabolic complications, including obesity, type 2 diabetes, hyperlipidemia, hypertension and metabolic syndrome [1,2]. Simple fatty liver itself may be considered a benign disorder, it can progress to hepatitis, fibrosis, and eventually lead to irreversible end-stage liver diseases such as cirrhosis and liver cancer. To control the onset and progression of fatty liver, it is important to inhibit lipogenesis in hepatocytes. Increasing evidence indicates that a large number of polyphenols naturally present in fruits and vegetables may be potential candidates for the treatment of NAFLD [3,4].
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