Introductory paragraphMacrophages exhibit a spectrum of activation states ranging from classical to alternative activation 1 . Alternatively, activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites 2 , improving insulin sensitivity 3 or promoting an immune tolerant microenvironment that facilitates tumour growth and metastasis 4 . Recently, the Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms *

Heart failure with preserved ejection fraction (HFpEF) is a growing public health concern, with rising incidence alongside high morbidity and mortality. However, the pathophysiology of HFpEF is not yet fully understood. The association between HFpEF and the metabolic syndrome (MetS) suggests that dysregulated lipid metabolism could drive diastolic dysfunction and subsequent HFpEF. Herein we summarise recent advances regarding the pathogenesis of HFpEF in the context of MetS, with a focus on impaired lipid handling, myocardial lipid accumulation and subsequent lipotoxicity.