A new study by Yan and colleagues reveals a mechanism that links obesity and ageing to hypothalamic inflammation, and thus to type 2 diabetes mellitus. In this study, an initial analysis found that production of transforming growth factor β (TGF-β) was excessive in obese and elderly mice. These excess levels of TGF-β were shown to cause hyperglycaemia and glucose intolerance, an effect that was independent of changes in body weight. Excess levels of TGF-β were demonstrated to induce a hypothalamic RNA stress response, which accelerated the mRNA decay of Iκβα (an inhibitor of proinflammatory nuclear factor κB). TGF-β was mainly produced and released by astrocytes and affected hypothalamic neurons, which resulted in metabolic dysfunction.