Dysregulated lipid metabolism links NAFLD to cardiovascular disease

Molecular Metabolism, Journal Year: 2020, Volume and Issue: 42, P. 101092 - 101092

Published: Oct. 1, 2020

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a global health problem. Cardiovascular diseases (CVD) are the most common cause of mortality in NAFLD patients. and CVD share several risk factors including obesity, insulin resistance, type 2 diabetes (T2D). Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense low-density lipoprotein (LDL) particles, decreased high-density cholesterol (HDL-C) levels, often observed patients.In this review, we highlight recent epidemiological studies evaluating link between risk. We further focus on mechanistic insights into links altered metabolism. also discuss current therapeutic strategies for their potential impact NAFLD-associated risk.Alterations hepatic lipid metabolism major contributing to patients, many promising NASH therapies development improve dyslipidemia clinical trials.

Language: Английский

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From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options

JHEP Reports, Journal Year: 2019, Volume and Issue: 1(4), P. 312 - 328

Published: July 19, 2019

The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to have reached 25% or more in adults. NAFLD prevalent obese individuals, but may also affect non-obese insulin-resistant individuals. associated with a 2- 3-fold increased risk developing type 2 diabetes (T2D), which be higher patients severe – fibrosis increases this risk. In NAFLD, not only the close association obesity, impairment many metabolic pathways, including decreased hepatic insulin sensitivity and secretion, increase T2D related comorbidities. Conversely, steatohepatitis, end-stage disease. Genetics mechanisms involving dysfunctional adipose tissue, lipotoxicity glucotoxicity appear play role. review, we discuss altered pathophysiological that underlie development vice versa. Although there no approved therapy for treatment NASH, pharmacological agents currently available treat could potentially useful management NASH.

Language: Английский

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Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics

Theranostics, Journal Year: 2019, Volume and Issue: 9(7), P. 1923 - 1951

Published: Jan. 1, 2019

Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component traditional Chinese Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest its pharmacological actions in treating and/or managing CVMD. Recent discoveries basic, translational clinical studies have identified many novel molecular targets (such as AMPK, SIRT1, LDLR, PCSK9, PTP1B) provided evidences supporting promising therapeutic potential combat Thus, this review provides a timely overview properties application CVMD, underlines recent advances which validate lead drug against

Language: Английский

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Targeting fibrosis: mechanisms and clinical trials

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 30, 2022

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including liver, kidney, heart, lung. such as liver cirrhosis, idiopathic pulmonary cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated various signals, transforming growth factor, platelet-derived fibroblast growh has been recongized a major event in occurrence progression fibrosis. Although mechanisms driving organ-specific have not fully elucidated, drugs targeting these identified aberrant signals achieved potent anti-fibrotic efficacy clinical trials. In this review, we briefly introduce aetiology epidemiology several diseases, kidney cardiac Then, summarise cells (epithelial cells, endothelial immune fibroblasts) their interactions addition, also focus on signaling pathways therapeutic targets that regulate myofibroblast activation, cross-linking, metabolism, inflammation Finally, discuss based This review provides reference for further research mechanism, drug development,

Language: Английский

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Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 18(1), P. 24 - 39

Published: Oct. 22, 2020

Language: Английский

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Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways

Clinical Science, Journal Year: 2022, Volume and Issue: 136(18), P. 1347 - 1366

Published: Sept. 1, 2022

Abstract The metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the combination with metabolic dysfunction form overweight or obesity and insulin resistance. It also associated an increased cardiovascular risk, including hypertension atherosclerosis. Hepatic lipid metabolism regulated by uptake export acids, de novo lipogenesis, utilization β-oxidation. When balance between these pathways altered, hepatic commences, long-term activation inflammatory fibrotic can progress to worsen disease. This review discusses details molecular mechanisms regulating lipids emerging therapies targeting as potential future treatments for MAFLD.

Language: Английский

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A role of peroxisome proliferator‐activated receptor γ in non‐alcoholic fatty liver disease

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2018, Volume and Issue: 124(5), P. 528 - 537

Published: Dec. 17, 2018

Non-alcoholic fatty liver disease is becoming a major health burden, as prevalence increases and there are no approved treatment options. Thiazolidinediones target the nuclear receptor peroxisome proliferator-activated γ (PPARγ) have been investigated in several clinical trials for their potential treating non-alcoholic (NAFLD) steatohepatitis (NASH). PPARγ has specialized roles distinct tissues cell types, although primary function of adipose tissue, where highest expression levels observed, hepatic significantly increased patients with NAFLD. Thus, NAFLD receiving agonists might response apart from one tissue. Owing to different PPARγ, new strategies include development compounds harnessing beneficial effects while restricting unwanted such adipogenesis resulting weight gain. Furthermore, dual or pan targeting two more PPARs shown promising results pre-clinical research some currently proceeding trials. This MiniReview explores adipose- liver-specific actions how this knowledge may contribute search modalities NAFLD/NASH.

Language: Английский

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Chronic Inflammation in Non-Alcoholic Steatohepatitis: Molecular Mechanisms and Therapeutic Strategies

Frontiers in Endocrinology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 14, 2020

Non-Alcoholic Steatohepatitis (NASH) is the progressive form of Fatty Liver Disease (NAFLD), main cause chronic liver complications. The development NASH consequence aberrant activation hepatic conventional immune, parenchymal, and endothelial cells in response to inflammatory mediators from liver, adipose tissue, gut. Hepatocytes, Kupffer sinusoidal contribute significant accumulation bone-marrow derived-macrophages neutrophils a hallmark NASH. these immune elicits harmful inflammation injury, leading progression. In this review, we highlight processes triggering recruitment and/or innate cells, with focus on macrophages, neutrophils, lymphoid as well contribution hepatocytes driving inflammation/fibrosis. On-going studies preliminary results global specific therapeutic strategies manage NASH-related will also be discussed.

Language: Английский

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Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Critical Reviews in Toxicology, Journal Year: 2021, Volume and Issue: 51(2), P. 141 - 164

Published: Feb. 7, 2021

Associations between per- and polyfluoroalkyl substances (PFASs) increased blood lipids have been repeatedly observed in humans, but a causal relation has debated. Rodent studies show reverse effects, i.e. decreased cholesterol triglycerides, occurring however at PFAS serum levels least 100-fold higher than those humans. This paper aims to present the main issues regarding modulation of lipid homeostasis by two most common PFASs, PFOS PFOA, with emphasis on underlying mechanisms relevant for Overall, apparent contrast human animal data may be an artifact dose, different molecular pathways coming into play upon exposure PFASs very low versus high levels. Altogether, interpretation existing rodent PFOS/PFOA-induced perturbations respect situation is complex. From mechanistic perspective, research liver cells shows that PFOS/PFOA activate PPARα pathway, whereas involvement other nuclear receptors, like PXR, are less conclusive. Other indicate suppression receptor HNF4α signaling as well bile acid metabolism transport might important cellular events require further investigation. Future human-relevant test systems would help obtain more insight pertinent These shall designed careful consideration appropriate dosing toxicokinetics, so enable biologically plausible quantitative extrapolations. Such will increase understanding possible perturbed related PFOS/ PFOA potential implications health.

Language: Английский

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PPAR-γ signaling in nonalcoholic fatty liver disease: Pathogenesis and therapeutic targets

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 245, P. 108391 - 108391

Published: March 22, 2023

Language: Английский

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