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Mechanisms of metabolic syndrome (MS) pathophysiology. MS is a result of a metabolic imbalance which involves alterations in different tissues and a variety of molecules. (1) Insulin resistance is accompanied by (2) a low-grade inflammation in the adipose tissue characterized by reduction of adipokines such as adiponectin, enhanced levels of leptin and resistin, accumulation of inflammatory cells in the adipose tissue, paralleled with high levels of cytokines/chemokines and reactive oxygen species. Alterations of the central (hypothalamus and the brainstem) and peripheral mechanisms of hunger and satiety occur (3). All these events contribute towards (4) decreased energy expenditure, hyperglycaemia and dyslipidaemia, increasing the risk for type 2 diabetes and cardiovascular diseases. Nutrient absorption (5) and the gut microbiota play key roles in the modulation of MS, aiding the connection between the brain and metabolic tissues. TG-triglycerides; VLDL-very low-density lipoprotein; CCK-cholecystokinin; Ecs-estrogens; GLP-1-glucagon-like peptide-1; GIP-gastric inhibitor peptide; TNFα-tumour necrosis factor α; IL-6-interleukin-6; MCP-1-macrophage chemotatic protein-1.
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Metabolic syndrome (MS) is a complex pathology characterized by visceral adiposity, insulin resistance, arterial hypertension, and dyslipidaemia. It has become a global epidemic associated with increased consumption of high-calorie, low-fibre food and sedentary habits. Some of its underlying mechanisms have been identified, with hypoadiponectinemia...
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Context 1
... metabolism is influenced by an intricate network of molecules released and receptors expressed within metabolic organs such as the pancreas, liver, adipose tissue and skeletal muscle, connecting the periphery to the brain (Figure 1). Hypoadiponectinemia, inflammation and oxidative stress [8][9][10][11][12] account for some of the mechanisms involved in MS establishment and progression, with a clear interplay between them. ...
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Purpose
It is unclear how the Chinese Visceral Adiposity Index (cVAI) relates to metabolic dysfunction-associated fatty liver disease (MAFLD) and alanine aminotransferase (ALT) in nonobese individuals. In this study, we evaluated the ability of the cVAI to predict MAFLD and elevated ALT in nonobese participants.
Methods
This cross-sectional study...
Citations
... (C) Schematic illustration of MIAM-based anti-HIV actions, which interprets the targeting and blocking of 3S peptide, preventing 3S peptide from interacting with gC1qR on CD4 + T cells, thereby stopping the cascade reactions that kill CD4 + T cells. Equilibrium binding isotherms of MIP (black) and NIP (grey) for 1.5 μM pep-rho (1); binding capacity of 100 μg MIP immobilized on a microplate with 3S peptide concentrations varying from 5 to 1500 nM (2). Reprinted, with permission, from [82]. ...
... (A) Pathophysiological mechanisms of metabolic syndrome, which is caused by a metabolic imbalance resulting from various organizational and different molecular changes. Reproduced, with permission, from[2]. (B) The microenvironment and signaling pathways caused cancer stemness. ...
Molecular imprints, which are crosslinked architectures containing specific molecular recognition cavities for targeting compounds, have recently transitioned from in vitro diagnosis to in vivo treatment. In current application scenarios, it has become an important topic to create new biomolecular recognition pathways through molecular imprinting, thereby inhibiting the pathogenesis and regulating the development of diseases. This review starts with a pathological analysis, mainly focusing on the corresponding artificial enzymes, enzyme inhibitors and antibody mimics with enhanced functions that are created by molecular imprinting strategies. Recent advances are highlighted in the use of molecular imprints as tailor-made nanomedicines for the prevention of three major diseases: metabolic syndrome, cancer, and bacterial/viral infections.
... In mammals, the TRP channel superfamily consists of TRPC, TRPM (melastatin), TRPV (vanilloid), TRPA (ankyrin), TRPP (polycystin), and TRPML (mucolipin) subfamilies 30 . TRP channels exhibit both pro-and anti-hepatic steatosis activity, evidenced by the observation that loss of TRPC5, TRPV1, and TRPM2 protected [31][32][33] , whereas loss of TRPV4 aggravated hepatic steatosis 34 . ...
Emerging evidence discloses the involvement of calcium channel protein in the pathological process of liver diseases. Transient receptor potential cation channel subfamily C member 3 (TRPC3), a ubiquitously expressed non-selective cation channel protein, controls proliferation, inflammation, and immune response via operating calcium influx in various organs. However, our understanding on the biofunction of hepatic TRPC3 is still limited. The present study aims to clarify the role and potential mechanism(s) of TRPC3 in alcohol-associated liver disease (ALD). We recently found that TRPC3 expression plays an important role in the disease process of ALD. Alcohol exposure led to a significant reduction of hepatic TRPC3 in patients with alcohol-related hepatitis (AH) and ALD models. Antioxidants (N-acetylcysteine and mitoquinone) intervention improved alcohol-induced suppression of TRPC3 via a miR-339-5p-involved mechanism. TRPC3 loss robustly aggravated the alcohol-induced hepatic steatosis and liver injury in mouse liver; this was associated with the suppression of Ca2+/calmodulin-dependent protein kinase kinase 2 (CAMKK2)/AMP-activated protein kinase (AMPK) and dysregulation of genes related to lipid metabolism. TRPC3 loss also enhanced hepatic inflammation and early fibrosis-like change in mice. Replenishing hepatic TRPC3 effectively reversed chronic alcohol-induced detrimental alterations in ALD mice. Briefly, chronic alcohol exposure-induced TRPC3 reduction contributes to the pathological development of ALD via suppression of the CAMKK2/AMPK pathway. Oxidative stress-stimulated miR-339-5p upregulation contributes to alcohol-reduced TRPC3. TRPC3 is requisite and a potential target to defend alcohol consumption-caused ALD.
... On the other hand, information on the involvement of TRP canonical channels 4 (TRPC4) and 5 (TRPC5) in weight and metabolic regulations remains scarce and deserves further investigation. As TRPC4 and TRPC5 can form homo-and heterotetramers between themselves and also with TRPC1, their roles in metabolic homeostasis are rather complex and have been recently discussed [33]. Interestingly, TRPC4 activation was found to modulate insulin secretion by triggering pancreatic cell depolarisation and Ca 2+ influx, and the disruption of TRPC1/TRPC5 signalling was demonstrated to result in an increased generation of adiponectin by adipocytes [34,35]. ...
... Inflammation is an important event that contributes to metabolic imbalances; thus, tumour necrosis factor α (TNFα) and vascular endothelial growth factor (VEGF) levels (inflammatory mediators involved in obesity and glycaemia control (for review see: [33,40])) were evaluated in adipose tissue, liver, and pancreas samples obtained from animals fed either a standard or HS diet. HS diet-fed mice led to a greater release of these inflammatory mediators in adipose tissue and liver samples in comparison with those receiving standard diet, an effect which was further enhanced by ML204 injection ( Figure 4A-D; p < 0.05). ...
... Also in agreement, HS significantly increased BMI, hyperglycaemia, mesenteric fat deposition, glucose tolerance, hypercholesterolemia, and NAS score in comparison with mice receiving a standard diet. In addition, HS-fed mice presented with adipose tissue and liver inflammation characterised by increased levels of TNFα, a cytokine involved in adipocyte hypertrophy, fat deposition, insulin resistance, and hyperglycaemia (for review see: [33]). Higher VEGF levels were also noted in both liver and adipose tissue samples from HS mice. ...
Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast, restaurant, and processed foods. Herein, we investigated the effects of a TRPC4/TRPC5 blocker, ML204, in the metabolic imbalances triggered by early exposure to sucrose-enriched diet in mice. TRPC4 and TRPC5 belong to the family of non-selective Ca+2 channels known as transient receptor potential channels. High-sucrose (HS)-fed animals with hyperglycaemia and dyslipidaemia, were accompanied by increased body mass index. mesenteric adipose tissue accumulation with larger diameter cells and hepatic steatosis in comparison to those fed normal diet. HS mice also exhibited enhanced adipose, liver, and pancreas TNFα and VEGF levels. ML204 exacerbated hyperglycaemia, dyslipidaemia, fat tissue deposition, hepatic steatosis, and adipose tissue and liver TNFα in HS-fed mice. Normal mice treated with the blocker had greater hepatic steatosis and adipose tissue cell numbers/diameter than those receiving vehicle, but showed no significant changes in tissue inflammation, glucose, and lipid levels. The results indicate that TRPC4/TRPC5 protect against the metabolic imbalances caused by HS ingestion.
... A possible mechanism implicated in the GT-mediated protection exerted on HFDinduced liver damage could implicate adipokines ( Figure 10). Indeed, alterations in adipokine levels are able to induce lipotoxicity and glucotoxicity in the liver with the development of steatosis through the involvement of TRP receptors [62]. Furthermore, according to data in the literature, naringenin-which we found to be specifically present in golden tomato-has been shown to act as a ligand for TRP receptors involved in many physiological processes that affect energy balance, inflammation, neuronal modulation, and oxidative stress [63][64][65]. ...
Tomato fruits defined as “golden” refer to a food product harvested at an incomplete ripening stage with respect to red tomatoes at full maturation. The aim of this study is to explore the putative influence of “golden tomato” (GT) on Metabolic Syndrome (MetS), especially focusing on the effects on redox homeostasis. Firstly, the differential chemical properties of the GT food matrix were characterized in terms of phytonutrient composition and antioxidant capacities with respect to red tomato (RT). Later, we assessed the biochemical, nutraceutical and eventually disease-modifying potential of GT in vivo in the high-fat-diet rat model of MetS. Our data revealed that GT oral supplementation is able to counterbalance MetS-induced biometric and metabolic modifications. Noteworthy is that this nutritional supplementation proved to reduce plasma oxidant status and improve the endogenous antioxidant barriers, assessed by strong systemic biomarkers. Furthermore, consistently with the reduction of hepatic reactive oxygen and nitrogen species (RONS) levels, treatment with GT markedly reduced the HFD-induced increase in hepatic lipid peroxidation and hepatic steatosis. This research elucidates the importance of food supplementation with GT in the prevention and management of MetS.
... Araújo et al. examined the literature about the role of the TRP-oxidative stress axis in the pathogenesis and progression of metabolic syndrome, focusing on TRPV1, TRPA1 and TRPC5 in regulating the function of metabolic tissues and cells, and their connections with the central nervous system. They also discussed the potential of such TRP channels as therapeutical targets for metabolic syndrome [8]. ...
It is well established that the accumulation of high levels of reactive oxygen species (ROS), due to excessive generation of ROS and/or impaired antioxidant capacity of cells, can result in oxidative stress and cause oxidative damage to cells and their functions [...]
... Consequently, increased ROS can decrease adiponectin, further inflammation, endothelial dysfunction, and insulin resistance. Further progression of this condition will cause hypertension, dyslipidemia, diabetes type 2, atherosclerosis, and even cancer (Araújo et al., 2022). Results from this study showed that KBPF intake could suppress ROS levels (ABTS, SOD data) as well as decrease major inflammatory cytokines (TNF-α, IL-6) significantly, potentially preventing the emergence and progression of metabolic disorders in its consumers (Fig. 10). ...
Clitoria ternatea, with an alternative name, Butterfly pea, is increasingly being explored for medical purposes and the development of a wide range of processed products. This study aimed to incorporate Butterfly pea into an innovative probiotic drink through a symbiotic culture of bacteria and yeast (SCOBY) fermentation and to evaluate the biological activity. The benefits of the drink, referred to as butterfly pea flower kombucha (KBPF) was determined in vitro and in metabolically disorder mice that receive a diet rich in cholesterol and fat (CFED). Forty white male were categorized into four groups, i.e., A = Control/Normal Diet; B = CFED alone; C = CFED + KBPF 65 mg/kg BW (Body Weight); D = CFED + KBPF 130 mg/kg BW, and then sacrificed after 6 weeks of intervention. Seventy-nine secondary metabolite compounds were successfully identified in KBPF using LC-HRMS. In vitro studies showed the potential activity of KBPF in inhibiting not only ABTS, but also lipid (lipase) and carhodyrate (α-amylase, α-glucosidase) hydrolyzing enzymes to levels similar to acarbose control at 50 – 250 μg/mL. In the in vivo study, the administration of KBPF (130 mg/kg BW) significantly alleviated metabolic disorders caused by high-fat diet. Specifically, lipid profile (HDL, LDL, TC, TG), blood glucose, markers of oxidative stress (SOD liver), metabolic enzymes (lipase, amylase), and markers of inflammation (PGC-1α, TNF-α, and IL-10) were in most cases restored to normal values. Additionally, the gut microbiota community analysis showed that KBPF has a positive effect (p=0.01) on both the Bacteroidetes phylum and the Firmicutes phylum. The new KBPF drink is a promising therapeutic functional food for preventing metabolic diseases.
Metabolic syndrome (MetS), with its high prevalence and significant impact on cardiovascular disease, poses a substantial threat to human health. The early identification of pathological abnormalities related to MetS and prevention of the risk of associated diseases is of paramount importance. Transient Receptor Potential (TRP) channels, a type of nonselective cation channel, are expressed in a variety of tissues and have been implicated in the onset and progression of numerous metabolism-related diseases. This study aims to review and discuss the expression and function of TRP channels in metabolism-related tissues and blood vessels, and to elucidate the interactions and mechanisms between TRP channels and metabolism-related diseases. A comprehensive literature search was conducted using keywords such as TRP channels, metabolic syndrome, pancreas, liver, oxidative stress, diabetes, hypertension, and atherosclerosis across various academic databases including PubMed, Google Scholar, Elsevier, Web of Science, and CNKI. Our review of the current research suggests that TRP channels may be involved in the development of metabolism-related diseases by regulating insulin secretion and release, lipid metabolism, vascular functional activity, oxidative stress, and inflammatory response. TRP channels, as nonselective cation channels, play pivotal roles in sensing various intra- and extracellular stimuli and regulating ion homeostasis by osmosis. They present potential new targets for the diagnosis or treatment of metabolism-related diseases.
