AKT/PKB Signaling: Navigating the Network

Cell, Journal Year: 2017, Volume and Issue: 169(3), P. 381 - 405

Published: April 1, 2017

Language: Английский

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SREBP-regulated lipid metabolism: convergent physiology — divergent pathophysiology

Nature Reviews Endocrinology, Journal Year: 2017, Volume and Issue: 13(12), P. 710 - 730

Published: Aug. 29, 2017

Language: Английский

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Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues

Molecular Aspects of Medicine, Journal Year: 2018, Volume and Issue: 65, P. 37 - 55

Published: Sept. 13, 2018

Language: Английский

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Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society

European Heart Journal, Journal Year: 2021, Volume and Issue: 42(47), P. 4791 - 4806

Published: July 30, 2021

Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for causal association between triglycerides (TG), TG-rich lipoproteins (TRL), TRL remnants, increased risk myocardial infarction, ischaemic stroke, aortic valve stenosis. These data also indicate that their remnants may contribute significantly to residual cardiovascular patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding the structure, function, metabolism TRL, pathophysiological role atherosclerotic disease (ASCVD). Key points are (i) working definition normo- hypertriglyceridaemic states relation ASCVD, (ii) conceptual framework generation due dysregulation production, lipolysis, remodelling, as well clearance remnant from circulation, (iii) pleiotropic proatherogenic actions at arterial wall, (iv) challenges defining, quantitating, assessing atherogenic properties particles, (v) exploration relative atherogenicity compared LDL. Assessment these issues provides foundation evaluating approaches effectively reduce levels by targeting either or hepatic clearance, combination mechanisms. consensus updates an integrated manner, thereby providing platform new therapeutic paradigms aim reducing ASCVD.

Language: Английский

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Lipid droplets and liver disease: from basic biology to clinical implications

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2017, Volume and Issue: 14(6), P. 343 - 355

Published: April 21, 2017

Language: Английский

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Direct effects of thyroid hormones on hepatic lipid metabolism

Nature Reviews Endocrinology, Journal Year: 2018, Volume and Issue: 14(5), P. 259 - 269

Published: Feb. 23, 2018

Language: Английский

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Pathophysiology of Diabetic Dyslipidemia

Journal of Atherosclerosis and Thrombosis, Journal Year: 2018, Volume and Issue: 25(9), P. 771 - 782

Published: July 11, 2018

Accumulating clinical evidence has suggested serum triglyceride (TG) is a leading predictor of atherosclerotic cardiovascular disease, comparable to low-density lipoprotein (LDL)-cholesterol (C) in populations with type 2 diabetes, which exceeds the predictive power hemoglobinA1c. Atherogenic dyslipidemia diabetes consists elevated concentrations TG-rich lipoproteins (TRLs), high prevalence small dense (LDL), and low cholesterol-rich high-density (HDL)2-C. A central abnormality an increase large very-low-density (VLDL)1, other abnormalities are metabolically linked increased TRLs. Insulin critically regulates VLDL by suppressing hepatic production stimulating removal activation lipase. It still debated whether hyperinsulinemia compensatory for insulin resistance causally associated overproduction VLDL. This review introduces experimental observations revealing that resistance, but not stimulates production. LDL HDL consist heterogeneous particles different size density. Cholesterol-depleted HDL2 subspecies particularly affected can be named "Metabolic HDL," respectively. We established direct assays quantifying LDL-C HDL(HDL3)-C, Subtracting HDL3-C from HDL-C gives HDL2-C. I will explain relevance measurements determined our assays. Diabetic kidney disease (DKD) substantially worsens plasma lipid profile thereby potentiated atherogenic risk. Finally, briefly overview pathophysiology DKD, been so much taken up articles.

Language: Английский

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Metabolic-associated fatty liver disease and lipoprotein metabolism

Molecular Metabolism, Journal Year: 2021, Volume and Issue: 50, P. 101238 - 101238

Published: April 20, 2021

Non-alcoholic fatty liver disease, or as recently proposed 'metabolic-associated disease' (MAFLD), is characterized by pathological accumulation of triglycerides and other lipids in hepatocytes. This common disease can progress from simple steatosis to steatohepatitis, eventually end-stage diseases. MAFLD closely related disturbances systemic energy metabolism, including insulin resistance atherogenic dyslipidemia. The the central organ lipid metabolism secreting very low density lipoproteins (VLDL) and, on hand, internalizing acids lipoproteins. review article discusses recent research addressing hepatic synthesis, VLDL production, lipoprotein internalization well exchange between adipose tissue context MAFLD. Liver triggered excessive triglyceride synthesis utilizing derived white (WAT), de novo lipogenesis (DNL) endocytosed remnants triglyceride-rich In consequence high content, secretion enhanced, which primary cause complex dyslipidemia typical for subjects with Interventions reducing secretory capacity attenuate while they exacerbate MAFLD, indicating that balance storage versus hepatocytes a critical parameter determining outcome. Proof concept studies have shown promoting combustion tissues reduces load thus ameliorates Moreover, hepatocellular DNL WAT-derived be targeted treat However, more needed understand how individual transporters, enzymes, their isoforms affect vivo, whether these two aspects selectively treated. Processing cholesterol-enriched appears less important steatosis. It may, however, modulate inflammation consequently progression.

Language: Английский

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An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans

Cell Metabolism, Journal Year: 2018, Volume and Issue: 27(3), P. 559 - 571.e5

Published: Feb. 15, 2018

Language: Английский

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Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy

Antioxidants, Journal Year: 2021, Volume and Issue: 10(2), P. 174 - 174

Published: Jan. 26, 2021

Oxidative stress (OxS) is considered a major factor in the pathophysiology of inflammatory chronic liver diseases, including non-alcoholic disease (NAFLD). Chronic impairment lipid metabolism closely related to alterations oxidant/antioxidant balance, which affect metabolism-related organelles, leading cellular lipotoxicity, peroxidation, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Increased OxS also triggers hepatocytes pathways, inflammation fibrogenesis, contributing progression steatohepatitis (NASH). The antioxidant response, regulated by Nrf2/ARE pathway, key component this process counteracts oxidative stress-induced damage, restoration normal metabolism. Therefore, modulation response emerges as an interesting target prevent NAFLD development progression. This review highlights link between disturbed context NAFLD. In addition, emerging potential therapies based on effects their likely molecular targets are discussed.

Language: Английский

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