Flavonoid-Induced Browning of White Adipose Tissue: A Strategy against Obesity-Associated Inflammation and Glucose Dysregulation

Obesity is a major global health concern that significantly contributes to the development of metabolic syndromes such as insulin resistance, type 2 diabetes, and chronic low-grade inflammation. White adipose tissue (WAT), the primary site for energy storage, can undergo “browning” to become metabolically active beige adipocytes, characterized by enhanced mitochondrial activity and uncoupling protein 1 (UCP1) expression. Recent research has identified flavonoids which is naturally occurring polyphenolic compounds abundant in fruits, vegetables, and plant-derived foods as potent inducers of WAT browning. This review comprehensively discusses the molecular mechanisms by which flavonoids promote the browning of WAT, focusing on the activation of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and the sympathetic nervous system. Additionally, we explore how flavonoid-induced browning alleviates obesity-related inflammation and improves glucose homeostasis. The therapeutic potential of various flavonoid subclasses such as catechins, anthocyanins, flavonols, and isoflavones is critically analyzed with supporting in vivo and in vitro evidence. We also highlight the translational challenges and future directions for clinical application. Flavonoid-based nutraceutical interventions represent a promising strategy to combat obesity and its associated metabolic disturbances through the induction of thermogenic adipocytes. Keywords: Flavonoids, White Adipose Tissue, Browning, Obesity, Inflammation, Glucose Dysregulation, Thermogenesis, UCP1, AMPK, PGC-1α