Attenuating Effects of Dieckol on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Decreasing the NLRP3 Inflammasome and Pyroptosis

Oh, Seyeon; Son, Myeongjoo; Byun, Kyung-A; Jang, Ji Tae; Choi, Chang Hyu; Son, Kuk Hui; Byun, Kyunghee

doi:10.3390/md19060318

Cited by 31 publications

(20 citation statements)

References 67 publications

(90 reference statements)

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“…Furthermore, HFD-induced NLRP3 inflammasome expression, including genes encoding NLRP3, ASC, and caspase-1, was decreased in response to dieckol. Moreover, the number of pyroptotic cells induced by a HFD was also reduced by the administration of dieckol ( Oh et al, 2021 ). Hence, dieckol inhibits lipid accumulation in the liver by increasing lipolysis and decreasing lipogenesis, which may be beneficial for the treatment of NAFLD.…”

Section: Pharmacological Agents Associated With Nlrp3 Inflammasome Su...mentioning

confidence: 99%

The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment

Wang

et al. 2022

Front. Pharmacol.

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Non-alcoholic fatty liver disease (NAFLD) is among the most prevalent primary liver diseases worldwide and can develop into various conditions, ranging from simple steatosis, through non-alcoholic steatohepatitis (NASH), to fibrosis, and eventually cirrhosis and hepatocellular carcinoma. Nevertheless, there is no effective treatment for NAFLD due to the complicated etiology. Recently, activation of the NLPR3 inflammasome has been demonstrated to be a contributing factor in the development of NAFLD, particularly as a modulator of progression from initial hepatic steatosis to NASH. NLRP3 inflammasome, as a caspase-1 activation platform, is critical for processing key pro-inflammatory cytokines and pyroptosis. Various stimuli involved in NAFLD can activate the NLRP3 inflammasome, depending on the diverse cellular stresses that they cause. NLRP3 inflammasome-related inhibitors and agents for NAFLD treatment have been tested and demonstrated positive effects in experimental models. Meanwhile, some drugs have been applied in clinical studies, supporting this therapeutic approach. In this review, we discuss the activation, biological functions, and treatment targeting the NLRP3 inflammasome in the context of NAFLD progression. Specifically, we focus on the different types of therapeutic agents that can inhibit the NLRP3 inflammasome and summarize their pharmacological effectiveness for NAFLD treatment.

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Section: Pharmacological Agents Associated With Nlrp3 Inflammasome Su...mentioning

confidence: 99%

The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment

Wang

et al. 2022

Front. Pharmacol.

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“…Saikosaponin-d, an active extract from Bupleurum falcatum used for the treatment of respiratory, inflammatory, and infectious diseases, reduced the liver FABP4 expression and protected against liver inflammation, endoplasmic reticulum, and oxidative stress [ 138 ]. Dieckol, a component of Ecklonia cava extracts with beneficial effects in inflammation, oxidation, and adipogenesis, attenuated the high fat diet liver induction of lipid accumulation and reduced the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome [ 139 ]. The mechanisms driving the liver lipid reduction by Dieckol include downregulation of the lipogenic genes, such as PPARγ and its target FABP4 , among others [ 139 ].…”

Section: Fabp4 As a Potential Therapeutic Target For Mafldmentioning

confidence: 99%

“…Dieckol, a component of Ecklonia cava extracts with beneficial effects in inflammation, oxidation, and adipogenesis, attenuated the high fat diet liver induction of lipid accumulation and reduced the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome [ 139 ]. The mechanisms driving the liver lipid reduction by Dieckol include downregulation of the lipogenic genes, such as PPARγ and its target FABP4 , among others [ 139 ]. The reduction in FABP4 expression, lipid accumulation, and inflammation by fatty acids was also observed in both HepG2 and Drosophila melanogaster models of liver steatosis treated with hydroethanolic extract of Lampaya medicinalis Phil .…”

Section: Fabp4 As a Potential Therapeutic Target For Mafldmentioning

confidence: 99%

Unveiling the Role of the Fatty Acid Binding Protein 4 in the Metabolic-Associated Fatty Liver Disease

et al. 2022

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Metabolic-associated fatty liver disease (MAFLD), the main cause of chronic liver disease worldwide, is a progressive disease ranging from fatty liver to steatohepatitis (metabolic-associated steatohepatitis; MASH). Nevertheless, it remains underdiagnosed due to the lack of effective non-invasive methods for its diagnosis and staging. Although MAFLD has been found in lean individuals, it is closely associated with obesity-related conditions. Adipose tissue is the main source of liver triglycerides and adipocytes act as endocrine organs releasing a large number of adipokines and pro-inflammatory mediators involved in MAFLD progression into bloodstream. Among the adipocyte-derived molecules, fatty acid binding protein 4 (FABP4) has been recently associated with fatty liver and additional features of advanced stages of MAFLD. Additionally, emerging data from preclinical studies propose FABP4 as a causal actor involved in the disease progression, rather than a mere biomarker for the disease. Therefore, the FABP4 regulation could be considered as a potential therapeutic strategy to MAFLD. Here, we review the current knowledge of FABP4 in MAFLD, as well as its potential role as a therapeutic target for this disease.

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“…The stained sections were visualized by light microscopy (Olympus Optical Co., Tokyo, Japan) and morphological changes were analyzed. NAFLD activity examination was performed in a blinded fashion using the following criteria [ 52 , 65 , 66 ]. The NAFLD activity score was measured using the following individual scores: (i) steatosis (0, <5%; 1, <33%; 2, <66%; 3, >66%), (ii) lobular inflammation (0, none; 1, <2 foci/200× field; 2, <4 foci/200× field; 3, >4 foci/200× field), and (iii) ballooning (0, none; 1, few balloon cells; 2, prominent ballooning).…”

Section: Methodsmentioning

confidence: 99%

Dieckol Decreases Caloric Intake and Attenuates Nonalcoholic Fatty Liver Disease and Hepatic Lymphatic Vessel Dysfunction in High-Fat-Diet-Fed Mice

Byun

Son

et al. 2021

Marine Drugs

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Increased inflammation is the main pathophysiology of nonalcoholic fatty liver disease (NAFLD). Inflammation affects lymphatic vessel function that contributes to the removal of immune cells or macromolecules. Dysfunctional lymphatic vessels with decreased permeability are present in NAFLD. High-fat diet (HFD) is known to increase body weight, food intake, and inflammation in the liver. Previously, it was reported that Ecklonia cava extracts (ECE) decreased food intake or weight gain, and low-calorie diet and weight loss is known as a treatment for NAFLD. In this study, the effects of ECE and dieckol (DK)—which is one component of ECE that decreases inflammation and increases lymphangiogenesis and lymphatic drainage by controlling lymphatic permeability in high-fat diet (HFD)-fed mice—on weight gain and food intake were investigated. ECE and DK decreased weight gain and food intake in the HFD-fed mice. NAFLD activities such as steatosis, lobular inflammation, and ballooning were increased by HFD and attenuated by ECE and DK. The expression of inflammatory cytokines such as IL-6 and TNF-α and infiltration of M1 macrophages were increased by HFD, and they were decreased by ECE or DK. The signaling pathways of lymphangiogenesis, VEGFR-3, PI3K/pAKT, and pERK were decreased by HFD, and they were restored by either ECE or DK. The expression of VE-cadherin (which represents lymphatic junctional function) was increased by HFD, although it was restored by either ECE or DK. In conclusion, ECE and DK attenuated NAFLD by decreasing weight gain and food intake, decreasing inflammation, and increasing lymphangiogenesis, as well as modulating lymphatic vessel permeability.

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Attenuating Effects of Dieckol on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Decreasing the NLRP3 Inflammasome and Pyroptosis

Cited by 31 publications

References 67 publications

The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment

The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment

Unveiling the Role of the Fatty Acid Binding Protein 4 in the Metabolic-Associated Fatty Liver Disease

Dieckol Decreases Caloric Intake and Attenuates Nonalcoholic Fatty Liver Disease and Hepatic Lymphatic Vessel Dysfunction in High-Fat-Diet-Fed Mice

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