Metabolic Spectrum of Liver Failure in Type 2 Diabetes and Obesity: From NAFLD to NASH to HCC

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(9), P. 4495 - 4495

Published: April 26, 2021

Liver disease is the spectrum of liver damage ranging from simple steatosis called as nonalcoholic fatty (NAFLD) to hepatocellular carcinoma (HCC). Clinically, NAFLD and type 2 diabetes coexist. Type contributes biological processes driving severity NAFLD, primary cause for development chronic diseases. In last 20 years, rate non-viral NAFLD/NASH-derived HCC has been increasing rapidly. As there are currently no suitable drugs treatment NASH, a class thiazolidinediones (TZDs) sometimes used improve failure despite risk side effects. Therefore, diagnosis, prevention, progression NASH important issues. this review, we will discuss pathogenesis NAFLD/NASH current promising pharmacological therapies NAFLD/NASH. Further, provide insights into “adipose-derived adipokines” “liver-derived hepatokines” diagnostic therapeutic targets HCC.

Language: Английский

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Metabolic causes and consequences of nonalcoholic fatty liver disease (NAFLD)

Metabolism Open, Journal Year: 2021, Volume and Issue: 12, P. 100149 - 100149

Published: Nov. 16, 2021

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that was first described in 1980. It has been prevalent and on the rise for many years associated with other disorders such as obesity type 2 diabetes mellitus (T2DM). NAFLD can be best dysfunction stems from insulin resistance-induced hepatic lipogenesis. This lipogenesis increases oxidative stress inflammation often potentiated by genetic gut microbiome dysfunction. As progresses simple steatosis to non-alcoholic steatohepatitis (NASH) cirrhosis hepatocellular carcinoma (HCC), odds of complications including cardiovascular (CVD), chronic kidney (CKD), overall mortality increase. The aim this review describe causes consequences while examining risks each stage poses. In review, etiology "lean" NAFLD, impact obesity, T2DM, genetics, dysbiosis progression are all explored. will also discuss core issue behind NAFLD: resistance (IR). Upon describing effectiveness diet modification, lifestyle changes, glucagon-like peptide 1 receptor (GLP-1) agonists retard stem rate examined.

Language: Английский

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PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4305 - 4305

Published: April 13, 2022

Peroxisome proliferator-activated receptors (PPAR), ligand-activated transcription factors of the nuclear hormone receptor superfamily, have been identified as key metabolic regulators in liver, skeletal muscle, and adipose tissue, among others. As a leading cause liver disease worldwide, non-alcoholic fatty (NAFLD) steatohepatitis (NASH) significant burden worldwide therapeutic strategies are needed. This review provides an overview evidence on PPAR-targeted treatment NAFLD NASH individuals with type 2 diabetes mellitus. We considered current from clinical trials observational studies well impact comorbid conditions such obesity, dyslipidemia, cardiovascular disease. Future areas research, possible sexually dimorphic effects therapies, briefly reviewed.

Language: Английский

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The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(13), P. 3649 - 3649

Published: June 24, 2022

Non-alcoholic fatty liver disease (NAFLD) represents a predominant hepatopathy that is rapidly becoming the most common cause of hepatocellular carcinoma worldwide. The close association with metabolic syndrome’s extrahepatic components has suggested nature systemic metabolic-related disorder based on interplay between genetic, nutritional, and environmental factors, creating complex network yet-unclarified pathogenetic mechanisms in which role insulin resistance (IR) could be crucial. This review detailed clinical evidence involved NAFLD–IR relationship, presenting both classic more innovative models. In particular, we focused reciprocal effects IR, oxidative stress, inflammation insulin-sensitivity disruption critical regions such as hepatic adipose tissue, while considering impact genetics/epigenetics regulation IR well nutrients specific insulin-related gene expression (nutrigenetics nutrigenomics). addition, discussed emerging capability gut microbiota to interfere physiological signaling hormonal pathways responsible for maintaining homeostasis by inducing an abnormal activation immune system. translation these novel findings into practice promote expansion accurate diagnostic/prognostic stratification tools tailored pharmacological approaches.

Language: Английский

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Nuclear factor erythroid 2-related factor 2-mediated signaling and metabolic associated fatty liver disease

World Journal of Gastroenterology, Journal Year: 2022, Volume and Issue: 28(48), P. 6909 - 6921

Published: Dec. 26, 2022

Oxidative stress is a key driver in the development and progression of several diseases, including metabolic associated fatty liver disease (MAFLD). This condition includes wide spectrum pathological injuries, extending from simple steatosis to inflammation, fibrosis, cirrhosis, hepatocellular carcinoma. Excessive buildup lipids strictly related oxidative MAFLD, progressing fibrosis cirrhosis. The nuclear factor erythroid 2-related 2 (NRF2) master regulator redox homeostasis. NRF2 plays an important role for cellular protection by inducing expression genes antioxidant, anti-inflammatory, cytoprotective response. Consistent evidence demonstrates that involved every step MAFLD deve-lopment, advanced ini-tiation/progression activators regulate lipid metabolism alleviating genes. Thus, modulating activation crucial not only understanding specific mechanisms underlying but also characterize effective therapeutic strategies. review outlined current knowledge on effects pathway, modulators, implications steatosis, MAFLD.

Language: Английский

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Implications of Resveratrol in Obesity and Insulin Resistance: A State-of-the-Art Review

Nutrients, Journal Year: 2022, Volume and Issue: 14(14), P. 2870 - 2870

Published: July 13, 2022

Background: Resveratrol is a polyphenol chemical that naturally occurs in many plant-based dietary products, most notably, red wine. Discovered 1939, widespread interest the potential health benefits of resveratrol emerged 1970s response to epidemiological data on cardioprotective effects Objective: To explore background (including its origins, stability, and metabolism), metabolic mechanisms action, future role lifestyle management obesity. Data sources: We performed narrative review, based relevant articles written English from Pubmed search, using following search terms: "resveratrol", "obesity", "Diabetes Mellitus", "insulin sensitivity". Results: Following ingestion, undergoes extensive metabolism. This includes conjugation (with sulfate glucuronate) within enterocytes, hydrolyzation reduction gut through action microbiota formation metabolites such as dihydroresveratrol), enterohepatic circulation via bile. Ex vivo studies adipose tissue reveal inhibits adipogenesis prevents accumulation triglycerides expression Peroxisome Proliferator-activated Receptor γ (PPARγ) sirtuin 1, respectively. Furthermore, induces anti-inflammatory effects, supported by animal-based studies. Limited human-based improves insulin sensitivity fasting glucose levels patients with Type 2 Diabetes Mellitus may improve inflammatory status human Although numerous underlie resveratrol, evidence supports interaction modulation protein targets, including sirtuins proteins related nitric oxide, insulin, nuclear hormone receptors (such PPARγ). Conclusions: Despite much interest, there remain important unanswered questions regarding optimal dosage (and how this differ between individuals), possible general population, for weight-loss improved function. Future should properly address these before we can advocate adoption supplementation.

Language: Английский

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Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 13, 2023

Oral semaglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1RA) designed for oral administration; it offers a promising opportunity to facilitate an early approach Type 2 Diabetes (T2D). The study aimed evaluate, in real-life setting, effects of on body composition patients with T2D after 26 weeks therapy.Thirty-two were evaluated at baseline (T0) and three (T3) six (T6) months therapy semaglutide. At each time point, was assessed using phase sensitive bioimpedance analyzer. Clinical, anthropometric laboratory parameters, main biometric surrogates liver steatosis fibrosis, also analyzed compared.A significant reduction glucometabolic alanine aminotransferase, Fatty Liver Index, Fat Mass observed. Visceral Adipose Tissue (VAT) decreased, while Free Skeletal Muscle (SMM) preserved during therapy, resulting beneficial increase SMM/VAT ratio. Finally, overall improvement fluid distribution observed.Our real-world data confirm clinical efficacy highlight its ability improve nutritional status T2D.

Language: Английский

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The Effect of Omega-3 Fatty Acids on Insulin Resistance

Life, Journal Year: 2023, Volume and Issue: 13(6), P. 1322 - 1322

Published: June 5, 2023

Insulin resistance is a critical pathophysiological process in the onset and advancement of type 2 diabetes mellitus. It well-recognized that alterations metabolism lipids aberrant fat buildup effectively trigger development to insulin. Adjusting one’s eating habits managing weight appropriately are crucial for treating, controlling, reducing risk T2DM because obesity lack physical exercise primary factors responsible worldwide rise T2DM. Omega-3 fatty acid one polyunsaturated acids (PUFA) include long-chain omega-3 such as eicosapentaenoic docosahexaenoic acid, commonly found fish oils. omega-6 (PUFAs; 3 6 PUFAs) essential human health they serve metabolic precursors eicosanoids, class signaling molecules controlling body’s inflammation. Since humans unable produce any or PUFAs, both constitute imperative nutritional ingredients. Long-standing concerns about acids’ impact on management have been supported by experimental investigations significant increases fasting glucose following supplementation foods rich PUFA acid. Cellular explanations explain connection between inflammation IR mitochondrial dysfunction, endoplasmic reticulum (ER) stress, oxidative stress. Modifications lipid composition membranes and/or receptor-mediated may be part mechanism behind activation fusion oil/omega-3 PUFA. The exact molecular processes which PUFAs control activity defend against still unknown.

Language: Английский

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Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: June 8, 2023

Obesity is a global epidemic and overwhelming evidence indicates that it risk factor for numerous cancers, including hepatocellular carcinoma (HCC), the third leading cause of cancer-related deaths worldwide. Obesity-associated hepatic tumorigenesis develops from nonalcoholic fatty liver disease (NAFLD), progressing to steatohepatitis (NASH), cirrhosis ultimately HCC. The rising incidence obesity resulting in an increased prevalence NAFLD NASH, subsequently represents increasingly important underlying etiology HCC, particular as other causes HCC such hepatitis infection, are declining due effective treatments vaccines. In this review, we provide comprehensive overview molecular mechanisms cellular signaling pathways involved pathogenesis obesity-associated We summarize preclinical experimental animal models available study features NAFLD/NASH/HCC, non-invasive methods diagnose NAFLD, NASH early-stage Finally, since aggressive tumor with 5-year survival less than 20%, will also discuss novel therapeutic targets ongoing clinical trials.

Language: Английский

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The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(11), P. 9084 - 9102

Published: Nov. 14, 2023

The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation liver. On other side, free fatty acid hepatocytes promotes via oxidative stress, endoplasmic reticulum lipotoxicity, increased secretion hepatokines. Cytokines adipokines cause resistance, thus promoting lipolysis adipose tissue ectopic fat deposition muscles Free acids along cytokines contribute to liver activation numerous signaling pathways. hepatokines, hormone-like proteins, primarily by disturbed impairs pathways, causing metabolic dysregulation ER stress unfolded protein response play significant roles aggravation through apoptosis, inflammatory response, impairment mediated IRE1/PERK/ATF6 pathways upregulation SREBP 1c. Circadian rhythm derangement biological clock desynchronization are related disorders, NAFLD, suggesting genes as a potential target for new therapeutic strategies. This review aims summarize mechanisms hepatic NAFLD development progression.

Language: Английский

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