Macrophages in metaflammation – fueling chronic inflammation in metabolic disease

Obesity is a leading global health issue, closely associated with a chronic low-grade inflammation termed metaflammation. Metaflammation is driven by immune cell reprogramming, particularly of macrophages. In white adipose tissue (WAT), obesity induces a shift from anti-inflammatory to pro-inflammatory macrophage phenotypes, contributing to insulin resistance and tissue fibrosis. Recent studies have also illuminated the role of macrophages in brown and beige adipose tissue (BAT and scWAT), where they influence thermogenic capacity. Beyond the adipose tissue, the liver is the other main metabolic organ impacted by obesity. Liver macrophages play a critical role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) by promoting inflammation, lipid accumulation, and fibrosis. This review highlights the role of macrophages in the development and regulation of metaflammation in metabolic organs.