Obesity’s Inflammatory Cascade Fuels Cancer, Cardiovascular Disease, Diabetes, and Fatty Liver
Obesity is commonly classified by body mass index (≥30 kg/m² obesity; 25–29.9 overweight), with lower cutoffs in some populations. It’s a growing global epidemic affecting over a billion people and driving major health and economic burden. Mechanistically, chronic energy surplus expands adipose tissue and promotes ectopic fat deposition. Adipose tissue acts as an endocrine/immune organ. With weight gain, it shifts toward low-grade inflammation with increased macrophage infiltration, higher pro-inflammatory cytokines/adipokines (eg, higher leptin), and lower adiponectin—setting up metabolic syndrome and insulin resistance.
These changes link obesity to cancer, cardiovascular disease, type 2 diabetes, and fatty liver disease. Inflammation, oxidative stress, lipid remodeling, and hyperinsulinemia/insulin-like growth factor signaling can promote tumor development and worse outcomes (with reported “obesity paradox” findings likely influenced by bias and measurement limits). Visceral and perivascular/epicardial fat contribute to hypertension, atherosclerosis, and heart failure via lipotoxicity, cytokines, and hemodynamic strain. Brown fat may be protective but is often reduced in obesity. For type 2 diabetes mellitus, free fatty acids and inflammatory signaling disrupt insulin pathways and impair β-cells; For non-alcoholic fatty liver disease/nonalcoholic steatohepatitis, insulin resistance and hepatic lipid overload drive steatosis, injury, fibrosis, and sometimes hepatocellular carcinoma. Treatment centers on diet/activity, bariatric surgery for selected patients, and medications (including GLP-1 receptor agonists), with ongoing need for therapies that improve cardiovascular outcomes.
Reference: Jin X, Qiu T, Li L, et al. Pathophysiology of obesity and its associated diseases. Acta Pharm Sin B. 2023 Jun;13(6):2403-2424. doi: 10.1016/j.apsb.2023.01.012.
Angela Ritten
DNP, ARNP, FNP-BC