Second-Generation Antipsychotics Induce Metabolic Disruption in Adipose Tissue-Derived Mesenchymal Stem Cells Through an aPKC-Dependent Pathway DOI Creative Commons
Marco Varalda,

Jacopo Venetucci,

Herald Nikaj

и другие.

Cells, Год журнала: 2024, Номер 13(24), С. 2084 - 2084

Опубликована: Дек. 17, 2024

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities, including visceral obesity, dyslipidemia, and insulin resistance. In this regard, white adipose tissue (vWAT) plays critical role, influencing energy metabolism, immunomodulation, oxidative stress. Adipose-derived stem cells (ADSCs) are key players in these processes within vWAT. While second-generation antipsychotics (SGAs) have significantly improved treatments for mental health disorders, their chronic use associated with an increased risk MetS. study, we explored the impact SGAs on ADSCs to better understand role MetS identify potential therapeutic targets. Our findings reveal that olanzapine disrupts lipid droplet formation during adipogenic differentiation, impairing receptor endocytosis, turnover, signaling. also alter endolysosomal compartment, leading acidic vesicle accumulation lysosomal biogenesis through TFEB activation. PKCζ crucial SGA-induced nuclear translocation formation. Notably, inhibiting restored tyrosine phosphorylation, normalized downstream signaling following treatment. This activation by driven phosphatidic acid synthesis via phospholipase D (PLD), G protein-coupled (GPCR) Overall, clozapine disrupt homeostasis PKCζ-dependent manner. These highlight as valuable tools uncovering cellular dysfunction vWAT may guide development new strategies mitigate side effects drugs.

Язык: Английский

Glycolipid Metabolic Disorders, Metainflammation, Oxidative Stress, and Cardiovascular Diseases: Unraveling Pathways DOI Creative Commons

Enzo Pereira de Lima,

Renato Cesar Moretti,

Karina Torres Pomini

и другие.

Biology, Год журнала: 2024, Номер 13(7), С. 519 - 519

Опубликована: Июль 12, 2024

Glycolipid metabolic disorders (GLMDs) are various resulting from dysregulation in glycolipid levels, consequently leading to an increased risk of obesity, diabetes, liver dysfunction, neuromuscular complications, and cardiorenal vascular diseases (CRVDs). In patients with GLMDs, excess caloric intake a lack physical activity may contribute oxidative stress (OxS) systemic inflammation. This study aimed review the connection between GLMD, OxS, metainflammation, onset CRVD. GLMD is due causing dysfunction synthesis, breakdown, absorption glucose lipids body, excessive ectopic accumulation these molecules. mainly neuroendocrine dysregulation, insulin resistance, metainflammation. many inflammatory markers defense cells play vital role related tissues organs, such as blood vessels, pancreatic islets, liver, muscle, kidneys, adipocytes, promoting lesions that affect interconnected organs through their signaling pathways. Advanced glycation end products, ATP-binding cassette transporter 1, Glucagon-like peptide-1, Toll-like receptor-4, sphingosine-1-phosphate (S1P) crucial since they glucolipid metabolism. The consequences this system organ damage morbidity mortality.

Язык: Английский

Процитировано

25

Why Are Perivascular Spaces Important? DOI Creative Commons
T. V. Shulyatnikova, Melvin R. Hayden

Medicina, Год журнала: 2023, Номер 59(5), С. 917 - 917

Опубликована: Май 10, 2023

Perivascular spaces (PVS) and their enlargement (EPVS) have been gaining interest as EPVS can be visualized non-invasively by magnetic resonance imaging (MRI) when viewing T-2-weighted images. are most commonly observed in the regions of basal ganglia centrum semiovale; however, they also identified frontal cortex hippocampal regions. known to increased aging hypertension, considered a biomarker cerebral small vessel disease (SVD). Interest has significantly because these PVS now an essential conduit necessary for glymphatic pathway provide efflux metabolic waste. Metabolic waste includes misfolded proteins amyloid beta tau that accumulate late-onset Alzheimer’s (LOAD) within interstitial fluid is delivered subarachnoid space eventually spinal (CSF). The CSF acts sink accumulating neurotoxicities allows clinical screening potentially detect if LOAD may developing early on its progression via examination. thought occur obstruction associates with excessive neuroinflammation, oxidative stress, vascular stiffening impairs flow due dampening arterial arteriolar pulsatility aids convective debris effluxing system. Additionally, associated Parkinson’s non-age-related multiple sclerosis (MS).

Язык: Английский

Процитировано

29

Overview and New Insights into the Metabolic Syndrome: Risk Factors and Emerging Variables in the Development of Type 2 Diabetes and Cerebrocardiovascular Disease DOI Open Access
Melvin R. Hayden

Опубликована: Фев. 7, 2023

Abstract Metabolic syndrome (MetS) is considered a metabolic disorder that has been steadily increasing globally and seems to parallel the prevalence of obesity. It consists cluster risk factors, which traditionally includes obesity hyperlipidemia, hyperinsulinemia, hypertension, hyperglycemia. These four core factors are associated with insulin resistance (IR) importantly, MetS known increase for developing cerebrocardiovascular disease type 2 diabetes mellitus. The had its early origins in IR X. undergone numerous name changes additional variables being added over years; however, it still remains worldwide past three decades. This overview continues add novel insights suggests leptin hyperleptinemia, aberrant mitochondrial stress reactive oxygen species (ROS), impaired folate-mediated one-carbon metabolism hyperhomocysteinemia, vascular stiffening, microalbuminuria, visceral adipose tissues extracellular vesicle exosomes be list variables. Notably, role dysfunctional activated endothelium deficient nitric oxide bioavailability along attenuated endothelial glycocalyx, inflammation, systemic metainflammation, important ROS interactome discussed. With new knowledge regarding MetS, comes possibility findings through further research.

Язык: Английский

Процитировано

18

A Closer Look at the Perivascular Unit in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus DOI Creative Commons
Melvin R. Hayden

Biomedicines, Год журнала: 2024, Номер 12(1), С. 96 - 96

Опубликована: Янв. 2, 2024

The recently described perivascular unit (PVU) resides immediately adjacent to the true capillary neurovascular (NVU) in postcapillary venule and contains normal-benign spaces (PVS) pathological enlarged (EPVS). PVS are important that they have been identified be construct conduit responsible for delivery of metabolic waste from interstitial fluid ventricular cerebrospinal disposal into systemic circulation, termed glymphatic system. Importantly, outermost boundary is lined by protoplasmic astrocyte endfeet (pvACef) communicate with regional neurons. As compared well-recognized NVU coupling, PVU less well understood remains an emerging concept. primary focus this narrative review compare similarities differences between these two units discuss each their structural functional relationships how relate not only brain homeostasis but also may development multiple clinical neurological disease states specifically obesity, syndrome, type 2 diabetes mellitus. Additionally, concept importance a perisynaptic coupling neuronal synapses pre- postsynaptic neurons will considered as provide creation information transfer via synaptic transmission homeostasis. Multiple electron microscopic images illustrations utilized order help explain complex units.

Язык: Английский

Процитировано

5

Revisiting Urban Street Planning and Design Factors to Promote Walking as a Physical Activity for Middle-Class Individuals with Metabolic Syndrome in Cairo, Egypt DOI Open Access
Hisham Abusaada, Abeer Elshater

International Journal of Environmental Research and Public Health, Год журнала: 2024, Номер 21(4), С. 402 - 402

Опубликована: Март 26, 2024

This paper revisits the planning and design factors of “pedestrianized” “walkable” urban streets to encourage physical activity, focusing on their prioritization according public health smart growth. The aim is create a conceptual framework for planners designers walking reduce metabolic syndrome (MetS) risks. Through scoping review, study found that while pedestrianized walkable share many factors, they have different objectives. explores how can MetS risk among middle-class individuals using online video storytelling 30 participants in three districts Cairo, Egypt: El Zamalek, Old Heliopolis. It identifies address symptoms individuals: strategic, design-oriented, technical. Practitioners policymakers use this evaluate impact work. particularly relevant cities Global South are facing similar challenges.

Язык: Английский

Процитировано

5

Brain Injury: Response to Injury Wound-Healing Mechanisms and Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus DOI Creative Commons
Melvin R. Hayden

Medicina, Год журнала: 2023, Номер 59(7), С. 1337 - 1337

Опубликована: Июль 20, 2023

Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury, termed response injury wound-healing (RTIWH) mechanism. When injured, regional endothelial cells initially undergo activation dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes, innate microglia, perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, resolution phases if injurious stimuli removed. In conditions wherein chronic, as occurs obesity, metabolic syndrome, type 2 diabetes mellitus, this process does not there is persistent RTIWH remodeling. Indeed, unique, that it utilizes its neuroglia: microglia cell, along peripheral inflammatory astroglia, instead scar-forming fibrocytes/fibroblasts. The undergoes astrogliosis form a gliosis scar fibrosis protect surrounding neuropil from parenchymal injury. One unique evolving remodeling changes development enlarged spaces (EPVSs), which focus brief review. EPVSs important since they serve biomarker for cerebral small vessel disease also represent an impairment effluxing glymphatic system clearance waste interstitial fluid cerebrospinal fluid, disposal. Therefore, better understand how mechanism involved closely associated premature age-related cerebrovascular neurodegenerative diseases impaired cognition.

Язык: Английский

Процитировано

11

Metabolic Syndrome and Psoriasis: Pivotal Roles of Chronic Inflammation and Gut Microbiota DOI Open Access
Paola Secchiero, Erika Rimondi, Annalisa Marcuzzi

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8098 - 8098

Опубликована: Июль 25, 2024

In recent years, the incidence of metabolic syndrome (MS) has increased due to lifestyle-related factors in developed countries. MS represents a group conditions that increase risk diabetes, cardiovascular diseases, and other severe health problems. Low-grade chronic inflammation is now considered one key aspects could be defined as new factor. Indeed, an visceral adipose tissue, typical obesity, contributes development inflammatory state, which, turn, induces production several proinflammatory cytokines responsible for insulin resistance. Psoriasis relapsing skin disease characterized by release pro-inflammatory cytokines, which can contribute different pathological within spectrum MS. A link between disorders emerged from evidence indicating weight loss obtained through healthy diets exercise was able improve clinical course therapeutic response patients with obesity or overweight even prevent its occurrence. factor this balance gut microbiota; it extremely dynamic system, makes manipulation diet possible via probiotic, prebiotic, symbiotic compounds. Given this, microbiota additional target metabolism conditions.

Язык: Английский

Процитировано

4

Use of Various Sugarcane Byproducts to Produce Lipid Extracts with Bioactive Properties: Physicochemical and Biological Characterization DOI Creative Commons
Joana Odila Pereira, Diana Oliveira, Margarida Faustino

и другие.

Biomolecules, Год журнала: 2024, Номер 14(2), С. 233 - 233

Опубликована: Фев. 17, 2024

Sugarcane, a globally cultivated crop constituting nearly 80% of total sugar production, yields residues from harvesting and production known for their renewable bioactive compounds with health-promoting properties. Despite previous studies, the intricate interplay extracts diverse sugarcane byproducts biological attributes remains underexplored. This study focused on extracting lipid fraction blend selected (straw, bagasse, filter cake) using ethanol. The resulting extract underwent comprehensive characterization, including physicochemical analysis (FT-IR, DSC, particle size distribution, color) chemical composition assessment (GC-MS). properties were evaluated through antihypertensive (ACE), anticholesterolemic (HMG-CoA reductase), antidiabetic (alpha-glucosidase Dipeptidyl Peptidase-IV) assays, alongside in vitro biocompatibility assessments Caco-2 Hep G2 cells. phytochemicals identified, such as β-sitosterol 1-octacosanol, likely contribute to extract's antidiabetic, anticholesterolemic, potential, given association various beneficial bioactivities. exhibited substantial effects, inhibiting α-glucosidase (5-60%) DPP-IV activity (25-100%), potential HMG-CoA reductase inhibition (11.4-63.2%), ACE (24.0-27.3%). These findings lay groundwork incorporating these ingredients into development food supplements or nutraceuticals, offering preventing managing metabolic syndrome-associated conditions.

Язык: Английский

Процитировано

3

Leptin and Insulin in COPD: Unveiling the Metabolic-Inflammatory Axis—A Narrative Review DOI Open Access

Oana Maria Catana,

Alexandra Floriana Nemeş,

Ramona Cioboată

и другие.

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(8), С. 2611 - 2611

Опубликована: Апрель 10, 2025

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating condition characterized by airflow limitations systemic inflammation. The interaction between the metabolic inflammatory pathways plays key role in progression, with leptin insulin emerging as pivotal regulators. Leptin, an adipokine that regulates energy homeostasis, insulin, primary regulator of glucose metabolism, are both altered COPD patients. This narrative review provides in-depth examination roles pathogenesis, focusing on molecular mechanisms through which these regulators interact how their dysregulation contributes to spectrum extrapulmonary manifestations. These disturbances not only exacerbate symptoms but also increase risk comorbidities such syndrome, diabetes, cardiovascular disease, or muscle wasting. By exploring underlying COPD, this underscores significance metabolic-inflammatory axis, suggesting restoring balance modulation could offer novel therapeutic strategies for improving clinical outcomes.

Язык: Английский

Процитировано

0

Assessing the association of multi-environmental chemical exposures on metabolic syndrome: A machine learning approach DOI Creative Commons

Yoon-Kyung Jo,

Mi-Yeon Shin,

Sungkyoon Kim

и другие.

Environment International, Год журнала: 2025, Номер 199, С. 109481 - 109481

Опубликована: Апрель 17, 2025

Metabolic syndrome (MetS) is a major global public health concern due to its rising prevalence and association with increased risks of cardiovascular disease type 2 diabetes. Emerging evidence suggests that environmental chemical exposures may play significant role in the development MetS by disrupting metabolic pathways. This study used data from 2,960 participants Korean National Environmental Health Survey (KoNEHS) cycle 4 (2018-2020) examine associations between risk through machine learning (ML) approaches. Eight ML algorithms were applied, multilayer perceptron (MLP) random forest (RF) models identified as optimal predictors. The MLP achieved an AUC 0.79, RF highest F1 score 0.82. Both highlighted PFOA PFOS, alongside age BMI, key SHapley Additive exPlanations (SHAP) partial dependence plots (PDP) revealed both linear nonlinear exposure-response patterns, suggesting threshold effects for chemicals. These findings underscore importance incorporating into assessments. provided robust predictive performance novel insights interactions, advocating regulatory measures reduce harmful integrate factors prevention strategies.

Язык: Английский

Процитировано

0