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As a chronic metabolic disorder characterized by pathological adipose tissue expansion, chronic inflammation, and neuroendocrine dysregulation that disrupts systemic homeostasis and impairs physiological functions, obesity is rarely an isolated condition; rather, it is frequently complicated by severe comorbidities that collectively elevate mortality risks. Despite advances in nutritional science and public health initiatives, sustained weight management success rates and prevention in obesity remain limited, underscoring its recognition as a multifactorial disease influenced by genetic, environmental, and behavioral determinants. Notably, the escalating prevalence of obesity and its earlier onset in younger populations have intensified the urgency to develop novel therapeutic agents that simultaneously ensure efficacy and safety. This review aims to elucidate the pathophysiological mechanisms underlying obesity, analyze its major complications\u2014including type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), non-alcoholic fatty liver disease (NAFLD), obesity-related respiratory disorders, obesity-related nephropathy (ORN), musculoskeletal impairments, malignancies, and psychological comorbidities\u2014and critically evaluate current anti-obesity strategies. Particular emphasis is placed on emerging pharmacological interventions, exemplified by plant-derived natural compounds such as berberine (BBR), with a focus on their molecular mechanisms, clinical efficacy, and therapeutic advantages. By integrating mechanistic insights with clinical evidence, this review seeks to provide innovative perspectives for developing safe, accessible, and effective obesity treatments.<\/jats:p>","DOI":"10.1186\/s43556-025-00264-9","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:46:44Z","timestamp":1745556404000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Obesity: pathophysiology and therapeutic interventions"],"prefix":"10.1186","volume":"6","author":[{"given":"Yue","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haokun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuxiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Nian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"issue":"6","key":"264_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3810\/pgm.2003.12.1544","volume":"114","author":"GA Bray","year":"2003","unstructured":"Bray GA. 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