GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids

Raptis, Dimitri Aristotle; Limani, Përparim; Jang, Jae Hwi; Ungethüm, U.; Tschuor, Christoph; Graf, Rolf; Humar, Bostjan; Clavien, Pierre‐Alain

doi:10.1016/j.jhep.2013.11.006

Cited by 99 publications

(95 citation statements)

References 33 publications

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“…Dietary V3FA comprise a number of fatty acids, of which EPA and DHA are the major constituents. Apart from modulating the composition and function of cell membranes, V3FA can activate specific receptors (eg, GPR120 12 ) and are further metabolized into a series of bioactive lipids (eg, resolvins, protectins), which participate in cellular signaling and are intermingled with other lipid signaling systems, such as by acting as ligands of cannabinoidtype receptors. 27,28 This underlying complexity suggests that detailed action mechanisms of V3FA will vary to provide dynamic responses toward specific situations.…”

Section: Discussionmentioning

confidence: 99%

“…10,33,34 We have previously shown that relieving steatosis-associated vasoconstriction via V3FA normalizes the oversensitivity toward I/R, 13 while V3FA-GPR120 mediated inhibition of inflammatory Kupffer cells protects lean liver akin to fasting. 12,25 Endothelial effects clearly will add, because sinusoids are the first to experience the consequences of ischemia. Proper endothelial function likewise is a prerequisite for liver regeneration after resection, 35 and the improvement of the defective regeneration seen in aged liver is associated with the reinstallation of vascular integrity.…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that V3FA reduce I/R injury in lean mouse liver via engagement of Gpr120, which imprints an anti-inflammatory M2 polarization phenotype onto Kupffer cells. 12 Likewise, V3FA were also effective against I/R in the ob/ ob model of NAFLD. 13 In addition, V3FA seem to improve recovery of lean liver from resection-induced liver failure, or of fatty liver after standard resection.…”

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confidence: 96%

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Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

et al. 2017

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Objective: The aim of this study was to assess the effect of V3 fatty acids (V3FA) on fatty and lean liver in hepatic surgery. Background: The global spread of energy-dense diets has led to an endemic rise in fatty liver disease and obesity. Besides metabolic pathologies, steatosis enhances hepatic sensitivity to ischemia reperfusion (I/R) and impedes liver regeneration (LR). Steatosis limits the application of liver surgery, still the main curative option for liver cancer. V3FA are known to reverse steatosis, but how these lipids affect key factors defining surgical outcomes-that is, I/R, LR, and liver malignancy-is less clear. Methods: We established a standardized mouse model of high fat diet (HFD)-induced steatosis followed by V3FA treatment and the subsequent assessment of V3FA effects on I/R, LR, and liver malignancy (n ¼ 5/group), the latter through a syngeneic metastasis approach. Fatty liver outcomes were compared with lean liver to assess steatosis-independent effects. Nonparametric statistics were applied. Results: V3FA reversed HFD-induced steatosis and markedly protected against I/R, improved LR, and prolonged survival of tumor-laden mice. Remarkably, these beneficial effects were also observed in lean liver, albeit at a smaller scale. Notably, mice with metastases in fatty versus lean livers were associated with improved survival. Conclusions: V3FA revealed multiple beneficial effects in fatty and lean livers in mice. The improvements in I/R injury, regenerative capacity, and oncological outcomes await confirmatory studies in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 96%

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Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

et al. 2017

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“…Concerning the fatty acid composition of Nigella crude oil, the current study showed that the oil is rich in omega-6 (60.4%) and omega-9 (25.2%) but scarce in omega 3-fatty acids (0.2%). Therefore, due to the role of omega-3 fatty acids as hepatoprotective and anti-inflamatory agents (Raptis et al, 2014;Al-Okbi and Mohamed, 2012), it was decided in the present study to blend Nigella crude oil with other omega-3 fatty acid rich oils from marine as well as plant origins such as fish and flaxseed oils, respectively.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the therapeutic effect of <em>Nigella sativa</em> crude oil and its blend with omega-3 fatty acid-rich oils in a modified hepatorenal syndrome model in rats

et al. 2015

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SUMMARY:In the present study, the hepato and reno-protective effect of Nigella sativa crude oil and its binary blend with omega-3 fatty acid-rich oils (fish and flaxseed oils) was studied in a modified hepatorenal syndrome model (MHRS) in rats. MHRS was induced through feeding a high fructose diet followed by an intraperitoneal injection of galactosamine hydrochloride. Nigella oil and its different blends were given as a daily oral dose to MHRS rats. Two control groups of MHRS and normal healthy rats were run. Different biochemical and nutritional parameters were assessed. The induction of MHRS produced liver and kidney dysfunction, and elevated oxidative stress, an inflammatory biomarker, endothelin 1, and plasma cholesterol. Reduced plasma high density lipoprotein cholesterol, albumin and Ca and elevated urinary N-acetyl-β-D-Glucosaminidase and liver fats were noticed. The administration of Nigella crude oil that originally had 0.2% total omega-3 fatty acids or its blend with fish oil (17.9% omega-3) or flaxseed oil (42.1% omega-3) significantly improved all biochemical parameters of MHRS. There was no significant difference in the biochemical parameters among the different oil treated groups regardless of the omega-3 fatty acid content. This may point out to the potential profound effect of the volatile oil fraction of Nigella crude oil which may compensates for its low omega-3 content. KEYWORDS: Hepatorenal syndrome; Nigella crude oil; Oil blends; Omega-3 fatty acidsRESUMEN: Evaluación del efecto terapéutico del aceite crudo de Nigella sativa y su mezcla con aceites ricos en ácidos grasos omega-3 en un modelo de síndrome hepatorenal modificado en ratas. En el presente estudio, el efecto hepato-y reno-protector de aceites crudos de Nigella sativa y su mezcla binaria con aceites ricos en ácidos grasos omega-3 (pescado y aceites de linaza) fue estudiado en un modelo modificado de síndrome hepatorenal (MHRS) en ratas. MHRS fue inducido a través de la alimentación de una dieta alta en fructosa seguido de la inyección intraperitoneal de clorhidrato de galactosamina. Diferentes aceites fueron suministrados como dosis oral diaria a ratas con MHRS. Se realizaron dos grupos de control de MHRS y ratas sanas normales. Se evaluaron diferentes parámetros bioquímicos y nutricionales. La inducción de la MHRS produce disfunción hepática y renal, elevado estrés oxidativo y biomarcadores inflamatorios, endotelina 1, y colesterol en plasma. Se observó una reducción del colesterol plasmatico de lipoproteínas de alta densidad, albúmina y Ca, elevación en orina de N-acetil-β-D-glucosaminidasa y de la grasa del hígado. La administración de aceite crudo de Nigella que tiene un 0,2% de ácidos grasos omega-3 totales o su mezcla con aceite de pescado (17,9% de omega-3) o aceite de linaza (42,1% de omega-3) mejoró significativamente todos los parámetros bioquímicos de MHRS. No hubo diferencia significativa en los parámetros bioquímicos entre los diferentes grupos tratados con los aceites ensayados independientemente del contenido de áci...

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“…Free radicals are known to involve in degeneration of cellular molecules and hence play role in aging, cancer, arteriosclerosis, and cirrhosis. Omega-3 fatty acids were shown to partially protect against these conditions by inhibiting development of ischemia, inflammation and production of free radicals [2,[16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Salgı

Karaman¹,

Özen²,

Dağ³

et al. 2016

Kafkas Univ Vet Fak Derg

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Omega-3 is a polyunsaturated fatty acid known to have immunomodulatory functions. In the present study, ameliorative potential of omega-3 in experimental carbon tetrachloride (CCl4) toxicity was investigated. Total of 40 adult male Wistar albino rats were allocated into five groups and were subcutaneously given once every two days for 6 weeks the followings: Group 1 (Control): 0.5 ml/kg serum physiologic, Group 2 (Omega): 0.5 g/kg omega-3, Group 3 (Vehicle): 0.5 ml/kg pure olive oil, Group 4 (CCl4): 0.5 ml/kg CCl4, Group 5 (CCl4 + Omega): 0.5 ml/kg CCl4 plus 0.5 g/kg omega-3. At the end of the treatments, blood samples were collected and necropsy was performed for collection of liver tissues. Serum AST, AlT, GGT, TAC, TOC, triglyceride, and visfatin levels were detected. liver morphology and immunoreactivities against TGF-α, TGF-β, PPAR-α, and PPAR-γ were assessed. Serum AST, AlT, GGT, and TOC levels significantly increased while TAC level decreased in CCl4 given animals as compared to the control group. No significant changes were observed in triglyceride and visfatin levels. Immunohistochemical staining revealed increased TGF-α and TGF-β expressions and decreased PPAR-α and PPAR-γ expressions in liver of CCl4 given animals. Omega-3 supplementation has prominent effects in correcting the biochemical and immunohistochemical parameters studied as well as the tissue morphology. The results of the investigation indicated that omega-3 has ameliorative effects on the oxidative tissue degeneration and inflammatory processes induced by CCl4 treatment in rats. Keywords: CCl4, Omega-3, TGF-α, TGF-β, PPAR-α, PPAR-γ Karbon Tetraklorür Toksikasyonunda Omega-3'ün Koruyucu Etkisi ÖzetOmega-3 bağışıklığı düzenleyici fonksiyonları olduğu bilinen çoklu doymamış bir yağ asididir. Bu çalışmada, deneysel karbon tetraklorür (CCl4) toksikasyonunda omega-3'ün koruyucu potansiyel etkisi araştırılmıştır. Toplam 40 adet ergin erkek Wistar albino rat eşit beş gruba ayrıldı ve 6 hafta süresince her iki günde bir olmak üzere subkutan yolla deneklere tarif edilen uygulamalar yapıldı; Grup 1 (kontrol): 0.5 ml/kg serum fizyolojik, Grup 2 (Omega): 0.5 g/kg omega-3, Grup 3 (Taşıt): 0.5 ml/kg saf zeytin yağı, Grup 4 (CCl4): 0.5 ml/kg CCl4, Grup 5 (CCl4 + Omega): 0.5 ml/kg CCl4 artı 0.5 g/kg omega-3. Araştırma süresinin sonunda, kan örnekleri alınan deneklere karaciğer doku örneklerinin toplanması amacıyla nekropsi uygulandı. Serum AST, AlT, GGT, TAC, TOC, trigliserid ve visfatin seviyeleri belirlendi. Karaciğer morfolojisi incelendi ve TGF-α, TGF-β, PPAR-α ve PPAR-γ immunreaktiviteleri tespit edildi. Kontrol grubu ile karşılaştırıldığında CCl4 verilen hayvanlarda serum AST, AlT, GGT ve TOC seviyelerinin anlamlı derecede arttığı, TAC seviyesinin ise azaldığı gözlemlendi. Trigliserid ve visfatin seviyelerinde anlamlı bir değişikliğin olmadığı belirlendi. İmmunohistokimyasal boyamalarda CCl4 verilen hayvanlarda TGF-α ve TGF-β immunreaktiviteleri artarken PPAR-α ve PPAR-γ immunreaktivitelerinde azalma dikkati çekti. Omega-3 takviyesinin incel...

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GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids

Cited by 99 publications

References 33 publications

Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

Evaluation of the therapeutic effect of <em>Nigella sativa</em> crude oil and its blend with omega-3 fatty acid-rich oils in a modified hepatorenal syndrome model in rats

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