The interplay of factors in metabolic syndrome: understanding its roots and complexity

Figures

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  Fig. 1. Schematic presentation of MetS. Multiple factors (genetics, age, lifestyle, overeating, inactivity, and smoking) lead to visceral adiposity, central to MetS. This adiposity triggers altered free fatty acid metabolism, promoting insulin resistance, dyslipidemia, and increased inflammation through markers like TNF, and IL-6. Additionally, adipokines (leptin, aldosterone) and the RAAS exacerbate chronic inflammation. These interconnected processes raise the risk of cardiovascular diseases like sudden cardiac death and hypertension, all key features of MetS. FFA: Free Fatty Acid, ATII: Angiotensin II, CRP: C-reactive protein, TNF: Tumor Necrosis Factor, IL-6: Interleukin 6, LOX: Lectin-like Oxidized, LDL: Low-Density Lipoprotein, ROS: Reactive Oxygen Species, RAAS; Renin Angiotensin Aldosterone System

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  Fig. 2. Pathophysiology of visceral obesity. Factors like inactivity, poor diet, and smoking cause positive energy balance, leading to visceral obesity and dysfunctional adipose tissue. These triggers altered fat metabolism and adipokine release, resulting in ectopic fat accumulation in organs like the heart, liver, and muscles, which ultimately drives MetS

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  Fig. 3. Schematic diagram of the mechanism action of insulin on an intracellular pathway. Insulin binds to the insulin receptor on the cell membrane, it triggers the phosphorylation (activation) of IRS (insulin receptor substrate) proteins. This, in turn, activates PI3-kinase, which converts PIP2 to PIP3, leading to the activation of AKT. Activated AKT promotes several downstream effects: it inhibits glycogen synthase kinase-3 (GSK3), which prevents glycogen breakdown and supports glycogen synthesis. AKT also facilitates the translocation of GLUT4 (a glucose transporter) to the cell membrane, enabling glucose uptake into the cell. Additionally, protein kinase A (PKA) is involved in the regulation of lipolysis, with insulin suppressing this process to reduce fat breakdown. The overall pathway enhances glucose uptake, glycogen storage, and reduces lipolysis, promoting energy storage and utilization. GLUT4: glucose transporter 4, PI-3: phosphoinositide-3, PIP2: phosphatidylinositol-4,5-bisphosphate, PIP3: phosphatidylinositol-3,4,5-triphosphate, PKA: protein kinase A

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  Fig. 4. Domination of INSR on MetS. The median expression of INSR in normal samples (bodymap) (a), Gene Gene interaction and their function (Physical Interaction, Genetic Interaction) (b, c). Overall Survival with high and low INSR units as transcript per million in Pancreatic adenocarcinoma (d), Overall Survival with high and low INSR units as transcript per million in Liver hepatocellular carcinoma (e), Overall Survival with high and low INSR unit as transcript per million in Lung adenocarcinoma (f). The INSR network is highly interconnected with various signaling pathways and that its expression can significantly influence survival outcomes in diseases like cancer or metabolic disorders. The survival carbs and bodymap were made by GEPIA (http://gepia.cancer-pku.cn/index.html). Gene–gene interaction was made from GeneMANIA (https://genemania.org/)