Gallstones in the Era of Metabolic Syndrome: Pathophysiology, Risk Prediction, and Management

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Gallstone disease (GSD) and metabolic syndrome (MetS) are increasingly prevalent conditions with significant global health implications. Recent evidence highlights a strong epidemiological association between these disorders, driven by shared pathophysiological mechanisms. This review provides comprehensive analysis of the intricate relationship MetS GSD, focusing on role insulin resistance, dyslipidemia, obesity, gut microbiota dysbiosis in gallstone formation. An integrated model is proposed, linking disturbances to bile cholesterol supersaturation, gallbladder dysmotility, chronic inflammation. The also explores clinical implications, including risk prediction models based parameters, early detection biomarkers, targeted interventions such as lifestyle modifications, pharmacological therapies, microbiome modulation. By addressing underpinnings this synthesis offers foundation for developing preventive therapeutic strategies mitigate burden interconnected conditions. Future research directions outlined refine mechanistic insights improve outcomes.

Language: Английский

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Mammalian Ste20-like kinase 1 regulates AMPK to mitigate the progression of non-alcoholic fatty liver disease

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: April 17, 2025

Abstract Background Non-alcoholic steatohepatitis (NASH) progression is strongly associated with deteriorating hepatic function, primarily driven by free cholesterol (FC) accumulation-induced lipotoxicity. Emerging evidence highlights the regulatory role of mammalian Ste20-like kinase 1 (MST1) in modulating intrahepatic lipid homeostasis, suggesting its therapeutic potential for non-alcoholic fatty liver disease (NAFLD) management. This investigation seeks to elucidate pathophysiological mechanisms through which MST1 modulates NASH progression. Methods The experimental design employed two murine genetic models—wild-type (WT) controls and MST1-knockout (MST1-KO) specimens—subjected a nutritionally modified Western diet (WD) enriched saturated fats, simple carbohydrates, dietary induce pathogenesis. Lentiviral transduction techniques facilitated targeted overexpression WT animals maintained on this regimen. Parallel vitro investigations utilized HepG2 hepatocyte cultures exposed acid (FFA) cocktails comprising palmitic oleic acids, coupled CRISPR-mediated suppression complementary gain-of-function manipulations delineate molecular mechanisms. Results triggers sterol biosynthesis activation, resulting pathological FC overload concurrent transcriptional suppression. Genetic ablation amplifies retention potentiates histopathological inflammation, while reconstitution mitigates steatotic deposition attenuates inflammatory cascades. Mechanistic profiling revealed MST1-mediated AMPKα phosphorylation at Thr172, suppresses cholesterogenic enzyme expression via element-binding transcription factor 2 (SREBP2) axis modulation. cascade demonstrates dose-dependent inhibition HMGCR activity, resolving FC-induced hepatotoxicity. Crucially, orchestrates AMPK/SREBP2 crosstalk maintain knockout models exhibiting 67% elevated SREBP2 nuclear translocation compared controls. Conclusions involving AMPK emerges as promising modality metabolism. It significant arresting cascades extracellular matrix remodeling characteristic studies confirm that effectively de novo lipogenesis enhancing efflux capacity, thereby establishing dual-target strategy against both metabolic dysfunction fibrotic transformation preclinical models.

Language: Английский

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Human adaptation response to obesity

International Journal of Obesity, Journal Year: 2025, Volume and Issue: unknown

Published: April 27, 2025

Language: Английский

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Autolysosomal Dysfunction in Obesity-induced Metabolic Inflammation and Related Disorders

Current Obesity Reports, Journal Year: 2025, Volume and Issue: 14(1)

Published: May 14, 2025

Language: Английский

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High-Fat Diet and Metabolic Diseases: A Comparative Analysis of Sex-Dependent Responses and Mechanisms

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4777 - 4777

Published: May 16, 2025

Sex differences in metabolic disorders and susceptibility to chronic diseases induced by a high-fat diet (HFD) exhibit significant dimorphic characteristics. A long-standing male-centric bias medical research healthcare, predominantly focused on male physiological traits, has hindered the precise treatment of female patients. comprehensive understanding sex health their underlying mechanisms is crucial for advancing personalized promotion precision medicine. This review systematically elucidates sex-specific manifestations diet-associated disorders: males develop visceral adiposity, insulin resistance, dyslipidemia, accompanied significantly elevated risk cardiovascular syndromes. Premenopausal females maintain homeostasis through estrogen-mediated optimization glucose lipid metabolism oxidative stress buffering mechanisms, whereas postmenopausal-phase experience dramatic vulnerability due z loss protective barriers. Furthermore, we emphasize multidimensional mechanistic interpretations sexual dimorphism from perspectives including chromosome complement, hormone signaling pathways, epigenetic regulation, gut microbiota composition, neuroendocrine dimorphism. work provides critical theoretical foundations rectifying unisex paradigms optimizing early warning systems therapeutic strategies disorders.

Language: Английский

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