Abstract

Obesity-associated diabetes, often referred to as diabesity, is a rapidly growing global health challenge 
characterized by impaired glucose homeostasis, insulin resistance, and progressive mitochondrial dysfunction. 
Mitochondria are central regulators of energy metabolism, orchestrating glucose oxidation, lipid utilization, and 
ATP generation. Their dysfunction exacerbates metabolic inflexibility and oxidative stress, contributing to the 
pathogenesis of obesity-linked diabetes. Natural products derived from plants, marine organisms, and microbial 
sources have gained attention as modulators of mitochondrial function due to their bioactive compounds, 
including polyphenols, flavonoids, alkaloids, terpenoids, and peptides. These agents restore mitochondrial 
integrity, enhance oxidative phosphorylation, stimulate biogenesis, and reduce excessive reactive oxygen 
species, thereby improving insulin sensitivity and metabolic health. This review examines the molecular 
mechanisms by which natural products ameliorate mitochondrial dysfunction and modulate energy metabolism 
in the context of obesity-associated diabetes. Particular emphasis is placed on signaling pathways such as 
AMPK, PGC-1α, and SIRT1, as well as the emerging therapeutic implications of these bioactives in clinical 
settings. 
Keywords: Natural products, Mitochondrial dysfunction, Energy metabolism, Obesity-associated diabetes, 
Bioactive compounds