Obesity has reached epidemic proportions globally, with its prevalence nearly tripling since 1975. It is now recognized as a chronic, relapsing disease associated with increased morbidity and mortality due to its strong relationship with several cardio-renal-metabolic conditions. This narrative review aims to explore the major obesity-related complications - namely obstructive sleep apnea syndrome (OSAS), metabolic dysfunction-associated steatotic liver disease (MASLD), dyslipidemia, and chronic kidney disease (CKD) - highlighting their pathophysiological mechanisms, clinical consequences, and current therapeutic strategies. Obesity contributes to OSAS by increasing upper airway collapsibility and to MASLD through ectopic fat accumulation, insulin resistance, and inflammatory responses. Dyslipidemia in obesity is characterized by elevated triglycerides, small dense LDL particles, and low HDL-C, driven by chronic inflammation and insulin resistance. CKD progression, particularly obesity-related glomerulopathy (ORG), is also mediated by metabolic and hemodynamic derangements, including renin-angiotensin-aldosterone system activation and glomerular hyperfiltration. Therapeutic interventions such as lifestyle modification, pharmacological therapy - including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) - and bariatric surgery have shown efficacy not only in promoting weight loss but also in improving the clinical course of these obesity-related conditions. In particular, Very Low Energy Ketogenic Therapy (VLEKT) is emerging as a promising approach in improving metabolic parameters, hepatic steatosis, and cardiovascular risk factors. A comprehensive and multidisciplinary approach to obesity is essential, focusing not only on weight loss but also on mitigating associated complications. Effective management can significantly improve patients' quality of life and reduce the long-term burden of obesity on healthcare systems.
