Exercise is a potent physiological stressor that disrupts cellular homeostasis and triggers a complex network of adaptive reactions. Heat shock proteins (HSPs), AMP-activated protein kinase (AMPK), and signaling pathways associated with inflammation are key modulators of this stress response. To restore energy balance and promote mitochondrial biogenesis, AMP/ATP ratio changes during exercise activate AMPK, a metabolic master switch. HSPs act as molecular chaperones, protecting protein integrity and promoting cellular resistance to mechanical, oxidative, and heat stress. Cytokine release, a hallmark of the acute inflammatory response to exercise, promotes tissue repair and adaptation; however, it can also have maladaptive effects when dysregulated. Emerging evidence suggests a complex and dynamic crosstalk between these pathways, wherein HSPs can inhibit inflammatory signaling and stabilize key proteins involved in energy metabolism. At the same time, AMPK modulates inflammatory cascades and influences the expression of HSPs. This review synthesizes the most recent findings from cellular and molecular studies.
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