Internal medicine

Receptor

Tumor necrosis factor alpha

Second messenger system

Necrosis

Medicine

Nature Metabolism

Tumour necrosis factor (TNF) is a classical, pleiotropic pro-inflammatory cytokine. It is also the first ‘adipokine’ described to be produced from adipose tissue, regulated in obesity and proposed to contribute to obesity-associated metabolic disease. In this review, we provide an overview of TNF in the context of metabolic inflammation or metaflammation, its discovery as a metabolic messenger, its sites and mechanisms of action and some critical considerations for future research. Although we focus on TNF and the studies that elucidated its immunometabolic actions, we highlight a conceptual framework, generated by these studies, that is equally applicable to the complex network of pro-inflammatory signals, their biological activity and their integration with metabolic regulation, and to the field of immunometabolism more broadly. Tumour necrosis factor is a classical pro-inflammatory cytokine. Sethi and Hotamisligil provide a comprehensive overview of its pleiotropic immunometabolic actions, while presenting a framework that is applicable to the complex network of other pro-inflammatory signals and their relevance to metabolic diseases such as obesity and diabetes.

Metabolic Messengers: tumour necrosis factor