Unraveling the Mystery of Insulin Resistance: From Principle Mechanistic Insights and Consequences to Therapeutic Interventions

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2770 - 2770

Published: March 19, 2025

Insulin resistance (IR) is a significant factor in the development and progression of metabolic-related diseases like dyslipidemia, T2DM, hypertension, nonalcoholic fatty liver disease, cardiovascular cerebrovascular disorders, cancer. The pathogenesis IR depends on multiple factors, including age, genetic predisposition, obesity, oxidative stress, among others. Abnormalities insulin-signaling cascade lead to host, insulin receptor abnormalities, internal environment disturbances, metabolic alterations muscle, liver, cellular organelles. complex multifaceted characteristics signaling envisage their thorough comprehensive understanding at molecular level. Therapeutic strategies for include exercise, dietary interventions, pharmacotherapy. However, there are still gaps be addressed, more precise biomarkers associated chronic lifestyle interventions needed. Understanding these pathways essential developing effective treatments IR, reducing healthcare costs, improving quality patient life.

Language: Английский

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Associations between cardiometabolic indices and the onset of metabolic dysfunction-associated steatotic liver disease as well as its progression to liver fibrosis: a cohort study

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 3, 2025

Abstract Background This study sought to examine the associations between cardiometabolic indices and onset of metabolic dysfunction-associated steatotic liver disease (MASLD) as well its progression fibrosis. Methods comprised 25,366 subjects aged 18 years older, free MASLD at baseline, from Dalian Health Management Cohort (DHMC). Cardiometabolic include index (CMI), atherogenic plasma (AIP), triglyceride glucose (TyG), glucose-body mass (TyG-BMI), glucose-waist circumference (TyG-WC) height ratio (TyG-WHtR). All participants were categorized into quartile groups based on indices. Cox proportional hazards regression models restricted cubic splines employed relationship incidence fibrosis, analyses performed different subgroups. Mediation analysis was explore how obesity inflammation serve mediators in connection MASLD. To evaluate predictive ability for MASLD, time-dependent receiver operating characteristic (ROC) curve utilized. Results A total 5378 (21.2%) individuals developed during follow-up period 82,445 person-years. Multivariates showed that highest had greater risk than those lowest (CMI: HR = 6.11, 95% CI 5.45–6.86; AIP: 4.58, 4.11–5.10; TyG: 3.55, 3.21–3.92; TyG-BMI: 13.55, 11.80–15.57; TyG-WC: 12.52, 10.93–14.34; TyG-WHtR: 11.37, 9.96–12.98). TyG-BMI (HR 1.36, 1.18–1.57), but not other indices, associated with indicated BMI mediated 40.4%, 33.2%, 36.5%, − 10.4%, 37.4%, 48.5% CMI, AIP, TyG, TyG-BMI, TyG-WC, TyG-WHtR Time-dependent ROC curves demonstrated a superior compared indicators. Conclusions The developing increases level increases. Obesity may mediating factor aforementioned association. strongest association proved be outperformed indicators, could best clinical non-invasive biomarker early screening

Language: Английский

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Hepatoprotective and Antiatherosclerotic Effects of Oleoylethanolamide-Based Dietary Supplement in Dietary-Induced Obesity in Mice

Pathophysiology, Journal Year: 2025, Volume and Issue: 32(2), P. 16 - 16

Published: April 18, 2025

Background: Metabolic effects of oleoylethanolamide-based dietary supplement (OEA-DS) were studied in a model dietary-induced obesity mice. Obesity was induced by 2-month high-fat, high-cholesterol diet, resulting significant morphological changes liver tissues and elevated cholesterol levels the animals’ blood serum. Elevated proinflammatory cytokines, oxidative stress, hepatocyte apoptosis also observed tissue. The aim this study to examine mechanisms through which an OEA-based exerts comprehensive influence on multiple aspects pathogenesis MASLD, thereby demonstrating robust hepatoprotective effect. Methods: mice fed diet with or without OEA-DS supplementation. Liver serum analyzed for levels, inflammatory markers (CD68, Iba-1, CD163, IL-1β, IL-6, TNFα), apoptotic (Bad, Bax, Bcl-2), nuclear receptors (PPAR-α, PPAR-γ, AdipoR1), enzymes involved lipolysis (Acox1, Cpt1a) metabolism (Ldlr, Furin, Pcsk9). Immunohistochemistry, Western blotting, RT-PCR used assess protein expression gene transcription. Results: administration normalized decreased (CD68 Iba-1), pro-apoptotic Bax) pro-inflammatory cytokines (IL-1β, TNFα). In parallel, PPAR-α adiponectin receptor 1 (AdipoR1), anti-inflammatory (CD163) anti-apoptotic (Bcl-2) have risen. factors Furin), while simultaneously reducing transcription proatherogenic factor Pcsk9. Conclusions: results suggest complex action obesity-associated damage, includes reduction systemic inflammation.

Language: Английский

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Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats

Molecules, Journal Year: 2025, Volume and Issue: 30(8), P. 1834 - 1834

Published: April 19, 2025

The rising prevalence of non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus has emerged as a global health challenge. Gossypetin (GTIN) is natural flavonoid which recently demonstrated antihyperglycaemic, antioxidant, and anti-inflammatory effects. Despite these findings, no studies have investigated its effects on in the pre-diabetic state. Hence, this study aimed to investigate GTIN diet-induced male rats presence absence dietary intervention compare those metformin (MET). Following 20 weeks pre-diabetes induction, animals were divided into six groups (n = 6) follows: non-pre-diabetic (NPD) control, (PD) PD treated (15 mg/kg body weight (bw)) or (500 bw) either normal diet high-fat, high-carbohydrate for 12 weeks. results showed that group had significantly higher triglycerides (TAG), weights, sterol regulatory binding element protein-1c (SREBP-1c), malondialdehyde (MDA) levels, injury enzyme along decreased superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) plasma bilirubin levels comparison NPD. Histologically, there was an increased lipid droplet accumulation structural disarray group. treatment reduced TAGs, SREBP-1c well improved SOD GPx activity while decreasing MDA enzymes control. Notably, levels. Liver histology GTIN-treated revealed tissue integrity. Similar observed parameters MET-treated groups. findings may suggest MET exhibit therapeutic both intervention. Dietary confer beneficial health, most favorable outcomes through combination Additionally, greater hepatoprotective than without

Language: Английский

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Association of cardiometabolic markers with hepatic steatosis and liver fibrosis in population without obesity and diabetes

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 5, 2025

The link between cardiometabolic markers and hepatic steatosis liver fibrosis in non-hypertensive, non-diabetic populations remains unclear. A study was conducted using data from the National Health Nutrition Examination Survey. Hepatic were assessed vibration-controlled transient elastography. Logistic regression restricted cubic splines (RCS) used to evaluate associations of index (CMI), atherogenic plasma (AIP), triglyceride-glucose (TyG), estimated glucose disposal rate (eGDR) on fibrosis. Mediation analysis examined role insulin resistance (HOMA-IR) enzymes. Among 1489 participants, 39.15% had 2.82% Higher CMI (OR = 3.967, 95%CI: 2.297, 6.851), AIP 3.255, 2.031, 5.216), TyG 3.689, 2.363, 5.760), FLI 2.695, 1.997, 7.816) tertiles Q3 linked increased odds, while eGDR reduced odds 0.217, 0.127, 0.373). AUC values these four cardiac greater than FLI, among which showed highest predictive value (AUC 0.781). In population, 1.419, 1.033, 2.747), 5.527, 1.082, 28.242), 2.345, 1.180, 4.661) also significant association with fibrosis, FIB-4 not associated discriminative ability for 0.798). HOMA-IR mediated 25.50%~36.20% markers' steatosis, followed by Cardiometabolic are strongly without traditional risk factors, even outperforming established marker, highlighting their potential early disease identification seemingly healthy individuals.

Language: Английский

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Strategy for treating MAFLD: Electroacupuncture alleviates hepatic steatosis and fibrosis by enhancing AMPK mediated glycolipid metabolism and autophagy in T2DM rats

Diabetology & Metabolic Syndrome, Journal Year: 2024, Volume and Issue: 16(1)

Published: Sept. 11, 2024

Language: Английский

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Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association

Diabetes & Metabolism Journal, Journal Year: 2024, Volume and Issue: 48(6), P. 1015 - 1028

Published: Nov. 22, 2024

Since the role of liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty disease (NAFLD) and dysfunction-associated (MAFLD) have shown associations between other diseases. Unlike exclusionary diagnostic criteria NAFLD, MAFLD diagnosis is based presence dysregulation disease. Renaming NAFLD as also introduced simpler criteria. In 2023, a new nomenclature, steatotic (SLD), proposed. Similar to MAFLD, SLD hepatic steatosis with at least one cardiometabolic dysfunction. categorized into (MASLD), dysfunction alcohol-related/-associated disease, alcoholrelated specific etiology SLD, cryptogenic SLD. The term MASLD has been adopted by number leading national international societies due its concise criteria, exclusion concomitant diseases, lack stigmatizing terms. This article reviews clinical relevance, differences among from diabetologist's perspective provides rationale for adopting SLD/MASLD Fatty Liver Research Group Korean Diabetes Association.

Language: Английский

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Strategy for treating MAFLD: Electroacupuncture alleviates hepatic steatosis and fibrosis by enhancing AMPK mediated glycolipid metabolism and autophagy in T2DM rats

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 10, 2024

Background: Recent studies havehighlighted type 2 diabetes (T2DM) as a significant risk factor for the development of metabolic dysfunction-associated fatty liver disease (MAFLD). This investigation aimed to assess electroacupuncture's (EA) impact on morphology and function in T2DM rats, furnishing experimental substantiation its potential stall MAFLD progression T2DM. Methods: rats were induced by high-fat diet single intraperitoneal injection streptozotocin, then randomly assigned five groups: group, electroacupuncture metformin combination group metformin, Compound C. The control received standard alongside citric acid - sodium citrate solution injections. After 6-week intervention, effects each fasting blood glucose, lipids, function, morphology, lipid droplet infiltration, fibrosis evaluated. Techniques including Western blotting, qPCR, immunohistochemistry, immunofluorescence employed gauge expression key molecules AMPK-associated glycolipid metabolism, insulin signaling, autophagy, pathways. Additionally, transmission electron microscopy facilitated observation droplets, fibrosis. Results: Our indicated that hyperglycemia, hyperlipidemia IR promoted accumulation, pathological functional damage, resulting hepatic steatosis Meanwhile, EA enhanced activation AMPK, which turn improved metabolism autophagy through promoting PPARα/CPT1A AMPK/mTOR pathway, inhibiting SREBP1c, PGC-1α/PCK2 TGFβ1/Smad2/3 signaling ultimately exerting effect ameliorating rats. above consistent with metformin. had advantages increasing AMPK expression, improving fibrosis, reducing serum ALT levels. In addition, partly disrupted C, an inhibitor AMPK. Conclusions: upregulated curtailing gluconeogenesis lipogenesis while boosting oxidation Consequently, it mitigated resistance thus impeding retarding advancement.

Language: Английский

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γ-Glutamylcysteine restores glucolipotoxicity-induced islet β-cell apoptosis and dysfunction via inhibiting endoplasmic reticulum stress

Toxicology and Applied Pharmacology, Journal Year: 2024, Volume and Issue: 495, P. 117206 - 117206

Published: Dec. 17, 2024

Language: Английский

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