Cellular senescence drives age-dependent hepatic steatosis

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: June 13, 2017

Abstract The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state irreversible cell-cycle arrest combined the secretion proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute age-related tissue degeneration. Here we show that accumulation senescent promotes hepatic fat steatosis. We report close correlation between markers hepatocyte senescence. elimination by suicide gene-meditated ablation p16 Ink4a -expressing in INK-ATTAC mice or treatment combination senolytic drugs dasatinib quercetin (D+Q) reduces overall Conversely, inducing vitro vivo . Mechanistically, mitochondria lose ability metabolize acids efficiently. Our study demonstrates cellular drives steatosis may be novel therapeutic strategy reduce

Language: Английский

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Triggering and resolution of inflammation in NASH

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2018, Volume and Issue: 15(6), P. 349 - 364

Published: May 8, 2018

Language: Английский

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Senolytic CAR T cells reverse senescence-associated pathologies

Nature, Journal Year: 2020, Volume and Issue: 583(7814), P. 127 - 132

Published: June 17, 2020

Language: Английский

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Recent Insights into the Pathogenesis of Nonalcoholic Fatty Liver Disease

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2018, Volume and Issue: 13(1), P. 321 - 350

Published: Jan. 24, 2018

Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic cardiometabolic mortality. The rapidly increasing prevalence of this its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches based on profound understanding pathogenesis to halt progression advanced fibrosis or cirrhosis cancer. NAFLD involves complex interaction among environmental factors (i.e., Western diet), obesity, changes in microbiota, predisposing genetic variants resulting disturbed lipid homeostasis excessive accumulation triglycerides other species hepatocytes. Insulin resistance central mechanism that leads lipotoxicity, endoplasmic reticulum stress, autophagy, and, ultimately, hepatocyte injury death triggers inflammation, stellate cell activation, progressive fibrogenesis, thus driving progression. In the present review, we summarize currently available data NAFLD, emphasizing most recent advances. A better NAFLD/NASH crucial design new efficient interventions.

Language: Английский

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Non-alcoholic fatty liver disease

BMC Medicine, Journal Year: 2017, Volume and Issue: 15(1)

Published: Feb. 20, 2017

Non-alcoholic fatty liver disease has emerged a major challenge because of it prevalence, difficulties in diagnosis, complex pathogenesis, and lack approved therapies. As the burden hepatitis C abates over next decade, non-alcoholic will become form chronic adults children could leading indication for transplantation. This overview briefly summarizes most recent data on pathophysiology, treatment disease. Ongoing clinical trials are focused an array mechanisms reviewed here how these treatments fit into current paradigm substrate overload lipotoxic injury. Many approaches directed at downstream events such as inflammation, injury fibrogenesis. Addressing more proximal processes dysfunctional satiety inappropriately parsimonious energy dissipation potential therapeutic opportunities that if successfully understood exploited would not only address but also other components metabolic syndrome obesity, diabetes dyslipidemia.

Language: Английский

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Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(4), P. 641 - 655

Published: April 1, 2019

Language: Английский

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Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases

International review of cell and molecular biology, Journal Year: 2018, Volume and Issue: unknown, P. 209 - 344

Published: Jan. 1, 2018

Language: Английский

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Role of inflammatory response in liver diseases: Therapeutic strategies

World Journal of Hepatology, Journal Year: 2018, Volume and Issue: 10(1), P. 1 - 7

Published: Jan. 26, 2018

Inflammation and tumorigenesis are tightly linked pathways impacting cancer development. Inflammasomes key signalling platforms that detect pathogenic microorganisms, including hepatitis C virus (HCV) infection, sterile stressors (oxidative stress, insulin resistance, lipotoxicity) able to activate pro-inflammatory cytokines interleukin-1β IL-18. Most of the inflammasome complexes have been described date contain a NOD-like receptor sensor molecule. Redox state autophagy can regulate complex and, depending on conditions, be either pro- or anti-apoptotic. Acute chronic liver diseases cytokine-driven as several proinflammatory (IL-1α, IL-1β, tumor necrosis factor-alpha, IL-6) critically involved in inflammation, steatosis, fibrosis, NLRP3 gain function aggravates disease, resulting severe fibrosis highlighting this pathway pathogenesis non-alcoholic fatty disease. On other hand, HCV infection is primary catalyst for progressive disease development cancer. It well established HCV-induced IL-1β production by hepatic macrophages plays critical central process promotes inflammation In review, we aim clarify role aggravation how selective blockade main may useful strategy delay progression diseases.

Language: Английский

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PPARs and nonalcoholic fatty liver disease

Biochimie, Journal Year: 2016, Volume and Issue: 136, P. 65 - 74

Published: Dec. 2, 2016

Language: Английский

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Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease

Journal of Hepatology, Journal Year: 2018, Volume and Issue: 69(6), P. 1349 - 1356

Published: Aug. 22, 2018

Language: Английский

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