Fasting protects liver from ischemic injury through Sirt1-mediated downregulation of circulating HMGB1 in mice

Rickenbacher, Andreas; Jang, Jae Hwi; Limani, Përparim; Ungethüm, U.; Lehmann, Kuno; Oberkofler, Christian E.; Weber, Achim; Graf, Rolf; Humar, Bostjan; Clavien, Pierre‐Alain

doi:10.1016/j.jhep.2014.04.010

Cited by 93 publications

(95 citation statements)

References 50 publications

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“…3A-C), known to be a key mediator of ischemic injury following reperfusion. 20 Moreover, although all measures led to Mmp8 induction, Il10 was most potently induced by RIPC (Fig. 3D, to 18 Finally, RIPC markedly reduced the gene expression of M1 polarization markers Emr1, Cd40, Nos2a, and Il12a (associated with proinflammatory Kupffer cell activity), whereas the IPC approaches had a little effect.…”

Section: Ripc Is Superior In Promoting Protective Signalingmentioning

confidence: 90%

“…Likewise, we assessed serum Hmgb1, because lowering prereperfusion Hmgb1 levels is strongly protective in IRI. 20 Furthermore, we measured markers of Kupffer cell polarization, as an M1>M2 polarization shift can mitigate IRI. 21 No measurements were done for IC, as this technique does not include a defined prereperfusion period.…”

Section: Ripc Is Superior In Promoting Protective Signalingmentioning

confidence: 99%

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Remote Ischemic Preconditioning

et al. 2016

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Section: Ripc Is Superior In Promoting Protective Signalingmentioning

confidence: 90%

Section: Ripc Is Superior In Promoting Protective Signalingmentioning

confidence: 99%

Remote Ischemic Preconditioning

et al. 2016

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“…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%

“…Likewise, marked reductions through V3FA treatment were noted for the injury markers ALT/AST, and for Hmgb1, released by necrotic cells and propagating parenchymal injury following reperfusion ( Figure 2B). 25 Therefore, V3FA treatment of mouse liver with diet-induced steatosis offers effective protection against hepatic I/R.…”

Section: V3fa Protect Fatty Liver Against Ischemia Reperfusionmentioning

confidence: 99%

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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“…It has been reported that cerebral ischemia can upregulate serum HMGB1 to stimulate the release of TNFα, IL-6, and other inflammatory factors to induce inflammation, which will contribute to cerebral ischemic injury (Yang et al 2010). Certain HMGB1 inhibitors or some physical methods can attenuate injuries caused by cerebral ischemia reperfusion or neonatal hypoxic-ischemic encephalopathy (Nakamura et al 2013;Rickenbacher et al 2014;Wang et al 2012). Furthermore, previous studies have suggested that there would be a certain relationship between HMGB1 and autophagy (Kang et al 2011;Thorburn et al 2009).…”

Section: Introductionmentioning

confidence: 99%

A Combination of Remote Ischemic Perconditioning and Cerebral Ischemic Postconditioning Inhibits Autophagy to Attenuate Plasma HMGB1 and Induce Neuroprotection Against Stroke in Rat

et al. 2016

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Remote ischemic perconditioning (RIPerC) and ischemic postconditioning (IPOC) are well-acknowledged neuroprotective procedures during ischemic injury. The present study established a combined RIPerC and IPOC (RIPerC + IPOC) model in rats and studied how it would regulate the autophagy process and affect HMGB1 levels in a rat model of middle cerebral artery occlusion (MCAO). Rats with MCAO were treated with RIPerC by fastening and release of the left hind limb to achieve 4 cycles of 5 min remote ischemia reperfusion, 40 min prior to cerebral reperfusion, and then treated with IPOC by exposing the cerebral middle artery to 3 cycles of 30 s reperfusion/30 s occlusion at the onset of cerebral reperfusion. Infarction volumes, neurological deficits, and pathological changes were assessed 24 h after ischemia. The autophagy activator rapamycin (RAP) and the autophagy inhibitor 3-methyladenine (3-MA) were administrated for further mechanism. The expression and location of HMGB1 and the autophagy-related proteins like LC3, Beclin1, and P62 as well as plasma HMGB1 levels were measured. Our results suggested that RIPerC + IPOC attenuated plasma HMGB1 levels to intensify its neuroprotective effect against cerebral ischemic reperfusion injury via inhibiting the autophagy process.

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Fasting protects liver from ischemic injury through Sirt1-mediated downregulation of circulating HMGB1 in mice

Cited by 93 publications

References 50 publications

Remote Ischemic Preconditioning

Remote Ischemic Preconditioning

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

A Combination of Remote Ischemic Perconditioning and Cerebral Ischemic Postconditioning Inhibits Autophagy to Attenuate Plasma HMGB1 and Induce Neuroprotection Against Stroke in Rat

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