Integrative metabolomics and proteomics of heat stress

Heat stress (HS) is an escalating global health concern driven by climate change. Despite increasing epidemiologic recognition, the molecular mechanisms underlying HS pathophysiology remains poorly defined. This review systematically synthesizes metabolomic and proteomic findings to elucidate these mechanisms and identify molecular targets for intervention. Current management remains limited to symptomatic relief, with no targeted therapies available to prevent or reverse HS-induced injury. To address this gap, metabolomics and proteomics offer powerful approaches for elucidating the molecular and cellular mechanisms underlying HS responses. Metabolomic studies demonstrate that HS disrupts central energy metabolism, promotes lipid remodeling, elevates oxidative stress, alters amino acid and sulfur metabolism, disrupts hormone regulation, and induces hepatic stress. Complementary proteomics studies reveal significant upregulation of heat shock proteins (HSPs), particularly HSP70 and HSP90, as well as remodeling of inflammatory mediators, cytoskeletal proteins, and signaling pathways. Together, these omics-based findings highlight a coordinated reprogramming of metabolic pathways and proteomic signatures that underpins both susceptibility and adaptation to HS. This review explores recent metabolomic and proteomic investigations into HS, underscoring how integrative multiomics approaches provide a coherent view of its molecular complexity. By bridging metabolite–protein crosstalk with therapeutic exploration, the review highlights how these insights advance the identification of biomarkers and molecular targets, ultimately guiding the development of more precise interventions for HS.