Effects of AMPK/PGC-1α on gluconeogenesis in skeletal muscle of animals under overwintering starvation and its molecular mechanism

Abstract

During winter feed deprivation, animals activate the sympathetic nervous system (SNS)-β-adrenergic receptor (βAR)-AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signaling pathway. This activation enhances the transcriptional activity of forkhead box O1 (FOXO1) and pyruvate dehydrogenase kinase 4 (PDK4), upregulates the expression of gluconeogenic rate-limiting enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and improves the function of carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 1 (UCP1), cluster of differentiation 36 (CD36), and fatty acid transport protein (FATP). These molecular adaptations facilitate intramuscular fat oxidation and glycerol production for gluconeogenesis, thereby enhancing skeletal muscle gluconeogenic capacity to maintain energy homeostasis and vital functions under cold-starvation conditions. This review systematically examines the effects of overwintering starvation stress on the AMPK/PGC-1α pathway and its regulatory mechanisms in skeletal muscle gluconeogenesis, providing a theoretical framework for developing sustainable breeding strategies in alpine regions and enhance animal production.

Keywords: AMP-activated Protein Kinase; Forkhead Box O1; Overwintering Starvation Stress; Peroxisome Proliferator-activated Receptor Gamma; Pyruvate Dehydrogenase Kinase 4; Skeletal Muscle Gluconeogenesis.