How Adipocytes Orchestrate Inflammation Within Adipose Tissue?

Abstract

Adipose tissue is far more than a passive reservoir for surplus energy: it is an active metabolic and endocrine organ that senses nutrient availability and orchestrates systemic energy balance. When caloric intake chronically exceeds expenditure, adipocytes become engorged with lipids and exposed to metabolic, mechanical, and hypoxic stress. To adapt, they initiate a fibro-inflammatory response that may be protective in the short term. As this response becomes chronic, adipocytes lose their metabolic flexibility, acquire a maladaptive fibro-inflammatory phenotype, and contribute to the cascade of inflammation, insulin resistance, and metabolic disease that characterizes obesity. In this review, we dissect the cellular and molecular cues that trigger fibro-inflammation, from nutrient excess and mitochondrial stress to hypoxia and immunometabolic rewiring, and highlight how these processes reshape adipocyte identity and tissue homeostasis.