Augmented Cardiac Growth Hormone Signaling in Circadian-Disrupted Cardiomyopathy: Mechanisms, Insights Insulin Resistance, and Chronopharmacological Targets

The heart is a highly metabolic organ whose function is tightly controlled by hormonal signals and the circadian clock. Disruption of cardiomyocyte clock genes, shift work, and misaligned light dark schedules have all been linked to cardiomyopathy and HFpEF like diastolic dysfunction. Emerging evidence suggests that local GH–IGF1 signaling in the heart is amplified when circadian timing mechanisms are disturbed, promoting hypertrophy, fibrosis, and altered substrate utilization. In parallel, systemic and cardiac insulin resistance are increasingly recognized as central contributors to heart failure pathophysiology. However, the specific ways in which augmented GH signaling in a circadian disrupted heart induces insulin resistance, reshapes myocardial energetics, and interacts with inflammatory and microvascular remodeling remain incompletely understood. A clearer mechanistic framework is needed to identify precise pharmacological and chronotherapeutic interventions.The goal of this Research Topic is to define how augmented cardiac GH signaling in the context of circadian disruption contributes to the development and maintenance of cardiomyopathy, with particular emphasis on insulin resistance and HFpEF like disease. We aim to gather studies that dissect molecular and cellular mechanisms, from GH receptor and STAT5 signaling to downstream metabolic, mitochondrial, and electrophysiological effects in cardiomyocytes and the cardiac microenvironment.At the same time, we seek to highlight work that bridges these mechanisms to translational endpoints: diastolic function, remodeling indices, imaging biomarkers, and clinical outcomes in patients with obesity, diabetes, sleep disruption, or shift work. A further objective is to explore how timing of hormone release and drug administration modulates these pathways, opening opportunities for chronopharmacological interventions. Together, these contributions should establish a more integrated view of GH-circadian-insulin crosstalk in the failing heart and identify testable strategies to modify this axis.We invite original research articles, brief reports, reviews, and mini‑reviews that address, but are not limited to, the following themes:1. Cardiac GH/GHR–IGF1–STAT5 signaling in genetic or environmental circadian disruption.2. Mechanisms of GH‑induced insulin resistance and metabolic inflexibility in cardiomyocytes3. Interactions between GH signaling, microvascular dysfunction, inflammation, and fibrosis in cardiomyopathy or HFpEF4. Omics‑based and imaging approaches to characterize GH and clock pathway remodeling in the heart5. Preclinical or clinical studies testing timing of GH/IGF1 modulation, insulin‑sensitizing drugs, or other chronopharmacological strategies in cardiometabolic heart disease Topic editors: RAVI SONKAR, Nicoleta-Monica Popa-Fotea Source: https://www.frontiersin.org/research-topics/80015/augmented-cardiac-growth-hormone-signaling-in-circadian-disrupted-cardiomyopathy-mechanisms-insights-insulin-resistance-and-chronopharmacological-targets