Visceral adiposity, metabolic health and aging.

Abstract

Visceral adipose tissue (VAT) is increasingly recognized as a metabolically active organ that contributes to systemic metabolic dysfunction and aging. Accumulation of VAT is thought not merely to be a biomarker of but also a causal contributor to impaired metabolic health and reduced lifespan. In this Review, we summarize evidence from both animal and human studies to evaluate whether this causal relationship truly holds. Our assessment indicates that VAT is not inherently harmful; rather, its pathogenicity is context dependent and emerges under specific conditions, including lipid spillover combined with impaired preadipocyte differentiation, chronic inflammation, genetic susceptibility, hormonal changes and aging. We further explore how VAT-derived cytokines, exosomes, adipokines and lipotoxic metabolites mechanistically mediate its harmful effects. Lastly, we outline both established and emerging strategies aimed at reducing VAT burden or neutralizing its pathological impact. These insights highlight the view of VAT as a modifiable and context-sensitive contributor to metabolic disease and aging, and a promising target for promoting metabolic health and longevity.