The Obesity Puzzle: Mechanisms, Consequences, and Cutting Edge Treatments

Abstract Obesity is now recognized as a chronic, relapsing, and multifactorial disease with profound implications for global health. Its prevalence has surged across all ages and populations, driving the epidemic of noncommunicable diseases, disability, and rising health care costs. This review summarizes current understanding of obesity from measurement and classification to epidemiology and underlying mechanisms, including neuroendocrine, genetic, developmental, adipose tissue-derived, microbiome, and environmental contributors. Major clinical consequences, cardiometabolic disease, cancer, and impaired quality of life, are highlighted alongside approaches for risk assessment and stratification. Evidence-based prevention and treatment strategies are examined, spanning lifestyle modification, pharmacotherapy, device-based therapies, and metabolic surgery. Particular attention is given to special populations (children, older adults, and pregnant women) and to issues of health system integration and equity. The recent advent of highly effective incretin-based therapies has transformed treatment paradigms, while raising questions about long-term safety, accessibility, and sustainability. We conclude by outlining the key research priorities necessary to translate these scientific advances into sustainable, population-level improvements in metabolic health. Keywords. obesity, BMI, adiposity, GLP-1, bariatric surgery, NAFLD.