The Adipose–Organ Communication Network in Clinical Obesity: From Adiposopathy to Systemic Metabolic Failure

The diagnostic landscape of obesity is transitioning from weight centric metrics toward a functional "clinical obesity" framework. This review explores the pathophysiology of adiposopathy ("sick fat"), where hypertrophic adipose tissue triggers systemic metabolic failure via the adipose-hepatic axis. Impaired subcutaneous adipose tissue (SAT) expandability, ectopic lipid accumulation, chronic inflammation, and maladaptive endocrine signaling are the hallmarks of adiposopathy ("sick fat"), a worldwide adipose tissue dysfunction. Through integrated adipose-organ communication networks, these changes support systemic cardiometabolic illness, MASLD, and hepatic insulin resistance. The molecular roles of DJ-1, Nrf2, and inflammatory kinases (JNK/IKKβ) in mediating this metabolic hit were examined in this study.