Scenario-based occupational risk assessment for power grid maintenance workers.

As the largest glucose-metabolizing organ in humans, skeletal muscle plays a pivotal role in maintaining systemic glucose balance and metabolic homeostasis (). Indeed, its exceptional glucose disposal capacity accounts for approximately 80% of postprandial glucose uptake and clearance (). Recent studies have revealed that skeletal muscle functions not merely as a contractile apparatus but also as an active endocrine organ. Under stimuli such as mechanical contraction, nutritional fluctuations, and metabolic stress, it secretes myokines and bioactive metabolites that orchestrate inter-organ communication. Through autocrine, paracrine, and endocrine mechanisms, these signaling molecules form an intricate metabolic network connecting muscle tissue with distal organs including the liver, adipose depots, and central nervous system (, ). For instance, irisin enhances glucose homeostasis by promoting the browning of white adipose tissue and improving insulin sensitivity, whereas the musclin has been identified as a negative regulator of systemic glucose homeostasis (, ). These discoveries not only redefine our comprehension of skeletal muscle physiology but also illuminate novel therapeutic avenues for metabolic disorders through targeted modulation of myokine signaling pathways. Recent advances in inter-organ metabolic communication research have shed light on the pivotal role of the skeletal muscle-liver axis in systemic glucose regulation. This axis constitutes a fundamental regulatory network whose dysregulation contributes significantly to metabolic disorders such as type 2 diabetes (T2D) (). A hallmark of T2D pathophysiology, fasting hyperglycemia, arises primarily from excessive hepatic gluconeogenesis (). As the largest peripheral metabolic organ, skeletal muscle is responsible not only for the majority of insulin-stimulated glucose uptake but also for precisely regulating key hepatic glucose metabolic pathways during metabolic challenges like fasting or exercise (). This regulation occurs through the secretion of myokines including IL-6, irisin, brain-derived neurotrophic factor (BDNF), and fibroblast growth factor 21 (FGF21), facilitating inter-organ communication to maintain glucose homeostasis. Notably, abnormalities in the skeletal muscle-liver communication network are directly associated with various metabolic pathologies (). Clinical evidence demonstrates that skeletal muscle-overexpressed FSTL1 in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) accelerates liver fibrosis progression (), while elevated circulating myogenic mitsugumin 53 levels induce systemic insulin resistance and hyperglycemia in T2D (). Remarkably, the newly discovered myokine feimin has shown therapeutic potential in improving hyperglycemia in diabetic models by activating the hepatic AKT signaling pathway, which simultaneously enhances glucose uptake and suppresses glucose production (). Although targeting inter-organ communication has emerged as a viable therapeutic strategy for treating metabolic diseases, the secretion mechanisms of key effector molecules in muscle-liver cross-talk remain unclear. Furthermore, the reprogramming of metabolic signaling networks under pathological conditions requires more in-depth investigation. Lactate dehydrogenase A (LDHA), the rate-limiting enzyme catalyzing the conversion of pyruvate to lactate, exhibits abundant expression in skeletal muscle (). Contemporary research has redefined lactate from a mere metabolic byproduct to a pivotal signaling molecule that coordinates systemic metabolism, particularly mediating skeletal muscle-liver cross-talk essential for maintaining glucose homeostasis (, ). Concurrently, histone post-translational modifications have been established as crucial epigenetic regulators of skeletal muscle physiology (). Emerging evidence reveals that lactate directly engages in epigenetic modification, with histone lactylation has emerged as a critical modulator in diverse physiological and pathological processes, including cell cycle regulation, hepatic stellate cell activation, and liver fibrosis (–). These findings collectively suggest that lactate metabolism may remodel the muscle-liver metabolic network via epigenetic mechanisms. Notably, as the primary site of lactate production, the potential role of histone lactylation in skeletal muscle for transcriptional regulation of myokines and its possible mediation of inter-organ communication between muscle and liver remains to be elucidated.