Rheumatic diseases and metabolism: where centre and periphery meet

Over the past few decades, the connection between metabolism and various inflammatory and rheumatic diseases has been an area of active investigation. Nonetheless, the precise mechanisms underlying these relationships remain a topic of ongoing debate, owing in part to conflicting data. This discrepancy can be attributed to the predominant focus on peripheral mechanisms in research into the metabolic consequences of rheumatic diseases. However, a wealth of evidence supports the notion that the central nervous system, specifically the hypothalamus, has an important influence on metabolic homeostasis. Notably, links have been established between crucial hypothalamic mechanisms responsible for regulating energy balance (including food intake, thermogenesis, and glucose and lipid metabolism), such as AMP-activated protein kinase, and the pathophysiology of rheumatoid arthritis. This Review aims to comprehensively examine the current understanding of central metabolic control in rheumatic diseases and explore potential therapeutic options that target this pathophysiological mechanism. In this Review, López and Gualillo discuss the complex interrelationships between rheumatic diseases and the hypothalamic and autonomic mechanisms that regulate metabolism, and explore the therapeutic potential of targeting central regulators of energy balance.