β-patchoulene improves lipid metabolism to alleviate non-alcoholic fatty liver disease via activating AMPK signaling pathway

Xu, Nan; Luo, Huijuan; Li, Minyao; Wu, Jingsong; Wu, Xue; Chen, Liping; Gan, Yuxuan; Guan, Fengkun; Li, Mengyao; Su, Zi‐Ren; Chen, Jiannan; Liu, Yuhong

doi:10.1016/j.biopha.2020.111104

Cited by 21 publications

(17 citation statements)

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“…CC is widely used as a cell-permeable ATP-competitive inhibitor of AMPK to revert the positive effects of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside and metformin [ 46 ]. CC treatment was reported to increase lipid and TG contents in hepatocytes [ 47 ], which is consistent with the current observation. On the contrary, CC has been demonstrated to be with AMPK-independent pharmacological actions.…”

Section: Discussionsupporting

confidence: 93%

Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy

et al. 2021

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Background Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic accumulation of triglycerides in the liver. Emerging evidence has demonstrated that lipophagy regulates lipid mobilization and energy homeostasis in the liver. Sirtuin 3 (SIRT3), a mitochondrial NAD+-dependent deacetylase, modulates the activities of several substrates involving in autophagy and energy metabolism. Honokiol (HK) is a natural lignan from the plants of Magnolia genus that exhibits potent liver protective property. Methods AML12 was challenged with 500 μM palmitic acid and 250 μM oleic acid mixture solution to induce lipotoxicity. C57BL/6J mice were fed with a choline-deficient high fat diet (CDHFD) to generate liver steatosis. The expression of autophagy-related and AMP-activated protein kinase (AMPK) pathway proteins was evaluated by Western blotting and immunofluorescence staining. Intracellular lipid accumulation was validated by Nile red staining. Molecular docking analysis was performed on AutoDock 4.2. Results HK (5 and 10 μM) was found to attenuate lipid accumulation through promoting SIRT3-AMPK-mediated autophagy, mainly on lipid droplets. HK had hydrophobic interaction with amino acid residues (PHE294, GLU323 and VAL324) and NAD+. Moreover, HK improved mitochondrial function to enhance lipolysis, through decreasing the acetylated long-chain acyl-CoA dehydrogenase level. In CDHFD-fed mice, HK (2.5 and 10 mg/Kg) treatment obviously prevented lipid accumulation in the liver. And co-treatment of the AMPK inhibitor, Compound C, almost abolished the above changes. Conclusions These results suggest that HK could ameliorate lipotoxicity in hepatocytes by activating SIRT3-AMPK-lipophagy axis, which might be a potential therapeutic agent against NAFLD.

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Section: Discussionsupporting

confidence: 93%

Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy

et al. 2021

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“…Studies reported that FAS could induce hepatocyte in ammation, which is highly associated with lipid accumulation in the liver. The fatty liver cell model was established using PA, OA, or a mixture of fatty acids (OA: PA) [6, 29,49]. Previously, DHA could alleviate OA-induced hepatocyte in ammation in grass carp, thus inhibiting the expression levels of transcription factors, such as IL-8, TNFα and NFκB [27].…”

Section: Discussionmentioning

confidence: 99%

“…During ER stress, the mRNA expression levels of related genes, including CHOP, GRP78, IRE1, ATF6 and PERK, were signi cantly decreased in the 1% DHA group (Figs. 3D and E We performed CCK8 analyses [29] to assess the cytotoxic effects of DHA, and determined the optimal concentration for hepatocyte experiments. Besides, 50 µM or 100 µM DHA did not display any toxicity in the cells, and co-treatment with 100 µM DHA prevented cytotoxic effects of PA (Fig.…”

Section: Dha Activates Ampk and Inhibits Er Stress Signaling Pathwaysmentioning

confidence: 99%

“…We prepared liver sample sections and stained them with H&E, as described previously [28]. These histological samples were observed and photographed under upright microscopy (Leica Biosystems, Germany), and relative cell viability was determined following standard instructions of the Cell Counting Kit-8 (K009-100T, Zeta Life Inc., USA) [29]. Brie y, hepatocytes were plated in a 96-well plate (1 × 10 4 cells/well) and cultured until these reached 85-90% con uence.…”

Section: Liver Histological Processing and Morphological Evaluation Cell Viability Assays And Nile Red Stainingmentioning

confidence: 99%

“…We performed CCK8 analyses [29] to assess the cytotoxic effects of DHA, and determined the optimal concentration for hepatocyte experiments. Besides, 50 µM or 100 µM DHA did not display any toxicity in the cells, and co-treatment with 100 µM DHA prevented cytotoxic effects of PA (Fig.…”

Section: Dha Activates Ampk and Inhibits Er Stress Signaling Pathwaysmentioning

confidence: 99%

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Docosahexaenoic Acid Lessens Hepatic Lipid Accumulation and Inflammation via the AMP-Activated Protein Kinase and Endoplasmic Reticulum Stress Signaling Pathway in Grass Carp (Ctenopharyngodon Idella)

Huang

Sun

Bian

et al. 2021

Preprint

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Background: The liver is the primary organ for frontline immune defense and lipid metabolism. Excessive lipid accumulation in the liver severely affects its metabolic homeostasis and causes metabolic diseases. Docosahexaenoic acid (DHA) is known for its beneficial effects on lipid metabolism and anti-inflammation, but its molecular mechanism remains unknown, especially in fish. In this study, we evaluated the protective effects of DHA on hepatic steatosis of grass carp (Ctenopharyngodon idella) in vivo and in vitro and mainly focused on lipogenesis and inflammation. Grass carp were fed with purified diets supplemented with 0%, 0.5% and 1% DHA for 8 weeks in vivo. Hepatocytes were treated with palmitic acid (PA) (200 μM) with or without DHA (50 or 100 μM) for 24 h in vitro. In addition, Compound C (CC, the inhibitor of AMP-activated protein kinase) was used to examine the mechanism of DHA on hepatic steatosis in vitro.Results: In this study, 1% DHA significantly decreased the liver triglyceride (TG), malondialdehyde (MDA), serum tumor necrosis factor α (TNFα) and nuclear factor kappa B (NFκB) contents. DHA (100 μM) effectively attenuated PA-induced lipid accumulation (P<0.05). Furthermore, DHA significantly inhibited endoplasmic reticulum (ER) stress and stimulated the expression of AMP-activated protein kinase (AMPK) and its downstream factors related to hepatic inflammation and lipogenesis in vivo and in vitro. However, the effects of DHA could be abrogated by CC in vitro.Conclusions: DHA exerted a protective effect on hepatic steatosis by inhibiting ER stress, improving antioxidant ability, relieving hepatic inflammation and inhibiting hepatic lipogenesis in an AMPK-dependent manner. Our findings give a theoretical foundation for further elucidation of the beneficial role of DHA in vertebrates.

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Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling

Zhang,

Lu,

Jiang

et al. 2023

Immunity Inflam & Disease

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BackgroundNonalcoholic fatty liver disease (NAFLD) is a primary contributor to liver‐related morbidity and mortality. Asprosin has been reported to be implicated in NAFLD.AimsThis work is to illuminate the effects of Asprosin on NAFLD and the possible downstream mechanism.Materials & MethodsThe weight of NAFLD mice induced by a high‐fat diet was detected. Quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) examined serum Asprosin expression. RT‐qPCR and western blot analysis examined Asprosin expression in mice liver tissues. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were implemented. Biochemical kits tested liver enzyme levels in mice serum and liver tissues. Hematoxylin and eosin staining evaluated liver histology. Liver weight was also tested and oil red O staining estimated lipid accumulation. RT‐qPCR and western blot analysis analyzed the expression of gluconeogenesis‐, fatty acid biosynthesis‐, fatty acid oxidation‐, and inflammation‐associated factors. Besides, western blot analysis examined the expression of AMP‐activated protein kinase (AMPK)/p38 signaling‐associated factors. In palmitic acid (PA)‐treated mice hepatocytes, RT‐qPCR and western blot analysis examined Asprosin expression. Lipid accumulation, gluconeogenesis, fatty acid biosynthesis, fatty acid oxidation, and inflammation were appraised again.ResultsAsprosin was overexpressed in the serum and liver tissues of NAFLD mice and PA‐treated mice hepatocytes. Asprosin interference reduced mice body and liver weight, improved glucose tolerance and diminished liver injury in vivo. Asprosin knockdown alleviated lipid accumulation and inflammatory infiltration both in vitro and in vivo. Additionally, Asprosin absence activated AMPK/p38 signaling and AMPK inhibitor Compound C reversed the impacts of Asprosin on lipid accumulation and inflammatory response.ConclusionCollectively, Asprosin inhibition suppressed lipid accumulation and inflammation to obstruct NAFLD through AMPK/p38 signaling.

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β-patchoulene improves lipid metabolism to alleviate non-alcoholic fatty liver disease via activating AMPK signaling pathway

Cited by 21 publications

References 35 publications

Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy

Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy

Docosahexaenoic Acid Lessens Hepatic Lipid Accumulation and Inflammation via the AMP-Activated Protein Kinase and Endoplasmic Reticulum Stress Signaling Pathway in Grass Carp (Ctenopharyngodon Idella)

Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling

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