Metabolic Syndrome (MetS) is a constellation of metabolic abnormalities that increase the risk of cardiovascular disease and type 2 diabetes mellitus. The diagnostic criteria for MetS include central obesity, insulin resistance, dyslipidemia, and hypertension. The prevalence of MetS has increased worldwide, and it is estimated that approximately 25% of the global adult population has MetS.
The molecular mechanisms underlying the development of MetS are complex and involve multiple pathways. Recent research has focused on identifying the molecular pathways involved in the pathogenesis of MetS and potential therapeutic targets. In this review, we discuss the molecular mechanisms of MetS and potential therapeutic targets.
Molecular mechanisms of metabolic syndrome
Insulin resistance: Insulin resistance is a key component of MetS and is defined as a reduced response to insulin in target tissues, such as muscle, liver and adipose tissue. Insulin resistance leads to impaired glucose uptake and increased hepatic glucose production, leading to hyperglycemia. The molecular mechanisms underlying insulin resistance involve dysregulation of multiple pathways, including inflammation, oxidative stress, and mitochondrial dysfunction.
Inflammation
Chronic low-grade inflammation is a hallmark of MetS and is thought to contribute to the development of insulin resistance. Inflammation is characterized by the activation of various pro-inflammatory cytokines, including Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-6 (IL-6) and C-Reactive Protein (CRP). These cytokines impair insulin signaling by activating serine/threonine kinases, such as c-Jun N-Terminal Kinase (JNK), Inhibitor of Kappa B Kinase (IKK), and Protein Kinase C (PKC), which phosphorylate Insulin Receptor Substrate-1 (IRS-1), leading to its degradation.