Diphlorethohydroxycarmalol Attenuates Palmitate-Induced Hepatic Lipogenesis and Inflammation

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.

Diphlorethohydroxycarmalol (DPHC) Isolated from the Brown Alga Ishige okamurae Acts on Inflammatory Myopathy as an Inhibitory Agent of TNF-α

“…In particular, DPHC is phlorotannin isolated from the EtOAc fraction of IOE, and DPHC was confirmed to be the main compound from the result of high performance liquid chromatography (HPLC) of the EtOAc fraction [37], and it was reported that it is the main compound showing various bioactivities via HPLC [34][35][36]38]. In addition, DPHC has been reported that exhibit anti-inflammatory activity [39][40][41], and it has also been reported to exhibit various bioactivities by regulating NF-κB signaling pathways, are a major pleiotropic transcription factor modulating immune, inflammatory, cell survival, and proliferative responses [35,[42][43][44]. IPA, another novel main phlorotannin identified from I. okamurae, was recently found to be involved metabolism such as diabetes and fat accumulation [45][46][47].…”

Docosahexaenoic acid lessens hepatic lipid accumulation and inflammation via the AMP-activated protein kinase and endoplasmic reticulum stress signaling pathways in grass carp (Ctenopharyngodon idella)

“…51 This study illustrated that the SREBP1c expression controlled several downstream-signaling components, including FAS and SD1 , consistent with other studies. 6,7,49,51 Besides, the above components were significantly upregulated in PA induction, which subsequently increased the TG content. However, DHA treatment could reverse these aberrant trends.…”

“…, FAS and SCD1). 6,49,50 In obese mice induced by diet, it exerted anti-hepatic steatosis effects when the activity of SREBP-1c was inhibited. 7 Similarly, liver-specific SREBP-1c knockout mice indicated that the expression levels of lipogenic-related enzymes, including ACC1, FASN and SCD1, were significantly reduced, and the hepatic lipid content and TG plasma levels were lower than those of wild-type mice.…”

“…The fatty liver cell model was established using PA, OA, or a mixture of fatty acids (OA : PA). 6,29,52 Previously, DHA could alleviate OA-induced hepatocyte inflammation in grass carp, thus inhibiting the expression levels of transcription factors, such as IL-8 , TNFα and NFκB . 27 PA is more toxic than other saturated or unsaturated fatty acids.…”

“…5 Fatty liver can cause hepatitis, fibrosis and irreversible end-stage liver diseases, such as liver cirrhosis and cancer. 6 Fat overload is a critical predisposing factor for hepatic steatosis. 7,8 Different studies have focused on lipid accumulation in response to other nutrients and key molecules causing hepatic steatosis.…”