Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation‑mediating treatment options (Review)

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 29(6)

Published: April 9, 2024

Obesity reaches up to epidemic proportions globally and increases the risk for a wide spectrum of co‑morbidities, including type‑2 diabetes mellitus (T2DM), hypertension, dyslipidemia, cardiovascular diseases, non‑alcoholic fatty liver disease, kidney respiratory disorders, sleep apnea, musculoskeletal disorders osteoarthritis, subfertility, psychosocial problems certain types cancers. The underlying inflammatory mechanisms interconnecting obesity with metabolic dysfunction are not completely understood. Increased adiposity promotes pro‑inflammatory polarization macrophages toward M1 phenotype, in adipose tissue (AT), subsequent increased production cytokines adipokines, inducing therefore an overall, systemic, low‑grade inflammation, which contributes syndrome (MetS), insulin resistance (IR) T2DM. Targeting mediators could be alternative therapies treat obesity, but their safety efficacy remains studied further confirmed future clinical trials. present review highlights molecular pathophysiological by chronic inflammation AT reactive oxygen species lead MetS, IR In addition, focus is given on role anti‑inflammatory agents, resolution through blockade chemotactic factors, such as monocytes chemotractant protein‑1, and/or mediators, IL‑1β, TNF‑α, visfatin, plasminogen activator inhibitor‑1, synthesis adiponectin apelin, obesity‑associated dysfunction.

Language: Английский

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Glutathione: Pharmacological aspects and implications for clinical use in non-alcoholic fatty liver disease

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: March 22, 2023

Glutathione is a tripeptide synthesized at cytosolic level, that exists in cells reduced form (thiol-reduced-GSH-) and an oxidized (disulfide-oxidized). The antioxidant function of GSH has led to speculation about its therapeutic role numerous chronic diseases characterized by altered redox balance levels, including, for instance, neurodegenerative disorders, cancer, liver diseases. Among these latter, non-alcoholic fatty disease (NAFLD), lipid accumulation hepatocytes, the absence alcohol abuse or other steatogenic factors, one most prevalent. umbrella term NAFLD includes pure fat accumulation, so-called hepatic steatosis liver, progressive with inflammation, also known as steatohepatitis, which related increase oxidative stress reactive oxygen species, eventually leading fibrosis. Although pathogenetic well established, there still limited evidence on such conditions. Hence, aim this review depict current molecular pharmacological knowledge glutathione, focusing available studies activity NAFLD.

Language: Английский

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Dietary Patterns, Foods, and Nutrients to Ameliorate Non-Alcoholic Fatty Liver Disease: A Scoping Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(18), P. 3987 - 3987

Published: Sept. 14, 2023

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic without pharmacological treatment yet. There also a lack specific dietary recommendations and strategies to treat negative health impacts derived from NAFLD. Objective: This scoping review aimed compile patterns, foods, nutrients ameliorate Methods: A literature search was performed through MEDLINE, Scopus, Web Science, Google Scholar. Results: Several guidelines are available literature. Hypocaloric Mediterranean diet accepted pattern tackle Coffee consumption (sugar free) may have protective effect for Microbiota plays role in NAFLD; hence, fibre intake should be guaranteed. Conclusions: high-quality could improve steatosis. Weight loss hypocaloric together with physical activity limited sugar good managing Specific plate been proposed

Language: Английский

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Exosomal miR‐122, miR‐128, miR‐200, miR‐298, and miR‐342 as novel diagnostic biomarkers in NAFL/NASH: Impact of LPS/TLR‐4/FoxO3 pathway

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 357(4)

Published: Jan. 22, 2024

Abstract Nonalcoholic fatty liver disease (NAFLD) is a common disorder affecting quarter of the global residents. Progression NAFL into nonalcoholic steatohepatitis (NASH) may cause cirrhosis, cancer, and failure. Gut microbiota imbalance causes microbial components translocation circulation, triggering inflammation NASH‐related fibrosis. MicroRNAs (miRNAs) regulate gene expression via repressing target genes. Exosomal miRNAs are diagnostic prognostic biomarkers for NASH damage. Our work investigated role gut in NAFLD pathogenesis lipopolysaccharide/toll‐like receptor 4/Forkhead box protein O3 (LPS/TLR‐4/FoxO3) pathway certain as noninvasive or its development to NASH. miRNA levels were measured using quantitative reverse transcription polymerase chain reaction (qRT‐PCR) 50 patients, normal controls. Plasma LPS, TLR‐4, adiponectin, peroxisome proliferator‐activated γ (PPAR‐γ), FoxO3 concentrations enzyme‐linked immunosorbent assay (ELISA). In miR‐122, miR‐128, FoxO3, PPAR‐γ upregulated while miR‐200, miR‐298, miR‐342, adiponectin downregulated compared with control. The examined might distinguish patients from control receiver operating characteristic analysis. study first examine these NAFLD. findings imply that potentially promising early diagnosis progression. Understanding LPS/TLR‐4/FoxO3 involvement NAFL/NASH aid management.

Language: Английский

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Oxidative stress in metabolic dysfunction‐associated steatotic liver disease (MASLD): How does the animal model resemble human disease?

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(3)

Published: Feb. 6, 2024

Abstract Despite decades of research, the pathogenesis metabolic dysfunction‐associated steatotic liver disease (MASLD) is still not completely understood. Based on evidence from preclinical models, one factors proposed as a main driver development oxidative stress. This study aimed to search for resemblance between profiles stress and antioxidant defense in animal model MASLD group patients. C57BL/6J mice were fed with Western diet up 24 weeks served MASLD. The profile hepatic tissue was determined by liquid chromatography‐MS3 spectrometry (LC–MS/MS). human cohort consisted 20 patients, who underwent bariatric surgery, 6 controls. histological analysis, 4 patients did have steatosis such also classified Total activity measured sera biopsy samples. levels enzymes damage Blot. significantly altered In contrast, there no significant changes except decreased level carbonylated proteins. Decreased protein carbonylation together correlations thioredoxin system parameters describing health suggest alterations thiol‐redox signaling. Altogether, these data show that even though phenotype closely resembles MASLD, animal‐to‐human translation cellular molecular processes may be more challenging.

Language: Английский

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Beneficial Effects of the Ketogenic Diet on Nonalcoholic Fatty Liver Disease (NAFLD/MAFLD)

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(16), P. 4857 - 4857

Published: Aug. 17, 2024

The prevalence of nonalcoholic fatty liver disease (NAFLD) is likely to be approaching 38% the world's population. It predicted become worse and main cause morbidity mortality due hepatic pathologies. particularly worrying that NAFLD increasingly diagnosed in children closely related, among other conditions, insulin resistance metabolic syndrome. Against this background concern awareness patients with low; one study, almost 96% adult USA were not aware their disease. Thus, studies on therapeutic tools used treat are extremely important. One promising treatment a well-formulated ketogenic diet (KD). aim paper present review available publications current state knowledge effect KD NAFLD. This includes characteristics key factors (from point view regression), which exerts its effects, i.e., reduction body weight, elimination fructose monosaccharides, limitation total carbohydrate intake, anti-inflammatory ketosis state, or modulation gut microbiome metabolome. In context evidence for effectiveness regression NAFLD, also suggests important role taking responsibility one's own health through increasing self-monitoring self-education.

Language: Английский

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Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review

Livers, Journal Year: 2023, Volume and Issue: 3(1), P. 33 - 53

Published: Jan. 12, 2023

The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk adverse events including injury. For more than 30 years, a series experimental clinical investigations reported or suggested that common pain reliever acetaminophen (APAP) could be hepatotoxic in obesity related metabolic diseases, at least after an overdose. Nonetheless, several did not reproduce these data. This discrepancy might come from extent steatosis, accumulation specific lipid species, mitochondrial dysfunction diabetes-related parameters such as ketonemia hyperglycemia. Among factors, some them seem pivotal for induction cytochrome P450 2E1 (CYP2E1), conversion APAP to toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). In contrast, other factors explain why NAFLD are always associated with frequent severe APAP-induced acute hepatotoxicity, increased volume distribution body, higher hepatic glucuronidation reduced CYP3A4 activity. Accordingly, occurrence outcome injury obese individual would depend on delicate balance between augment generation NAPQI others can mitigate hepatotoxicity.

Language: Английский

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Correlation of Metabolic Syndrome with Redox Homeostasis Biomarkers: Evidence from High-Fat Diet Model in Wistar Rats

Antioxidants, Journal Year: 2022, Volume and Issue: 12(1), P. 89 - 89

Published: Dec. 30, 2022

Metabolic Syndrome (MetS) is an extremely complex disease. A non-balanced diet such as high-fat (HFD) induces metabolic dysfunction that could modify redox homeostasis. We here aimed at exploring homeostasis in male Wistar rats, following 8 weeks of HFD, correlating the eventual modification selected biomarkers be associated with clinical manifestations MetS. Therefore, we parameters relative to both glucose tolerance and lipid altered metabolism, but also oxidative pattern. assessed some stress i.e., thiols balance, peroxidation antioxidant barriers, via use specific biochemical assays, individuating cross correlation MetS through a Principal Component Analysis (PCA). The present study shows HFD induce altering increasing visceral adipose tissue, impairing physiological responses not counteract condition. Crucially, cross-correlation analysis suggested assessment reported can provide information comparable more widely acquired Mets tolerance. Lastly, hepatic steatosis association condition was highlighted by histological analysis. This research will elucidate fundamental impact these on induced rat model, tracing paths for developing prevention approaches.

Language: Английский

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The Role of Growth Hormone and Insulin Growth Factor 1 in the Development of Non-Alcoholic Steato-Hepatitis: A Systematic Review

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 517 - 517

Published: Feb. 4, 2023

Diabetic and obese patients have a high prevalence of non-alcoholic fatty liver disease (NAFLD). This condition groups spectrum conditions varying from simple steatosis to steatohepatitis (NASH), with or without fibrosis. Multiple factors are involved in the development NAFLD. However, details about its pathogenesis that promote progression NASH still missing. Growth hormone (GH) insulin-like growth factor 1 (IGF-1) regulate metabolic, immune, hepatic stellate cell functions. Increasing evidence suggests they may roles NAFLD NASH. Following PRISMA reporting guidelines, we conducted systematic review evaluate all clinical experimental studies published literature correlating GH IGF-1 inflammation fibrosis Our results showed fundamental role NASH, acting slightly different ways produce synergic effect. Indeed, mediate protective effect by regulating lipogenesis pathways, while has same cholesterol transport. Therefore, could be used as therapeutic strategies preventing

Language: Английский

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Rising Influence of Nanotechnology in Addressing Oxidative Stress-Related Liver Disorders

Antioxidants, Journal Year: 2023, Volume and Issue: 12(7), P. 1405 - 1405

Published: July 9, 2023

Reactive oxygen species (ROS) play a significant role in the survival and decline of various biological systems. In liver-related metabolic disorders such as steatohepatitis, ROS can act both cause consequence. Alcoholic steatohepatitis (ASH) non-alcoholic (NASH) are two distinct types steatohepatitis. Recently, there has been growing interest using medications that target formation reduce levels therapeutic approach for oxidative stress-related liver disorders. Mammalian systems have developed antioxidant defenses to protect against excessive generation. These modulate through series reactions, limiting their potential impact. However, condition worsens, exogenous antioxidants become necessary control levels. Nanotechnology emerged promising avenue, utilizing nanocomplex efficient nano-antioxidants. demonstrate enhanced delivery site, minimizing leakage improving targeting accuracy. Therefore, it is essential explore evolving field nanotechnology an effective means lower establish interventions

Language: Английский

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