Branched-Chain Amino Acids Target miR-203a/fosb Axis to Promote Skeletal Muscle Growth in Common Carp (Cyprinus carpio)

Abstract

Starvation is an environmental stress that cannot be ignored during the growth of aquatic animals. Amino acid composition and balance can influence the nutritional effects, regulating the anabolic metabolism and energy signaling in the organism. Among these, branched-chain amino acids (BCAAs), which are essential amino acids in fish, play vital roles in energy regulation and growth metabolism. In order to observe the recovery effect of BCAAs in sustained duration starvation of common carp, a 4-week starvation period was initiated, followed by a 4-week feeding period with different concentrations of compound BCAAs (leucine:isoleucine:valine = 2:1:1). The detection of skeletal muscle protein deposition, muscle proliferation and differentiation, and indicators related to muscle atrophy at the conclusion of the culture period was conducted. Prior research has demonstrated that microRNA-203a (miR-203a) plays a role in the adaptive regulation of organisms under conditions of energy stress. To further investigate the target-related relationship among BCAAs, miR-203a, and FosB proto-oncogene, AP-1 transcription factor subunit (fosb), an in vitro transfection procedure was conducted in conjunction with topical injections of fosb small interfering RNA (siRNA), a miR-203a antagomir, an EEF2K (eukaryotic elongation factor-2 kinase) inhibitor, and an 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR) activator. The findings indicated that BCAAs can effectively mitigate muscle damage resulting from starvation, with the 18 g/kg BCAAs diet group demonstrating the most pronounced recovery effect. At the molecular level, BCAAs can regulate the AMPK (adenosine 5‘-monophosphate [AMP]-activated protein kinase) pathway through the miR-203a-mediated targeting of fosb, thereby facilitating muscle protein deposition and muscle cell regeneration, ultimately mitigating muscle atrophy. In conclusion, supplementing the diet with BCAAs enhances skeletal muscle protein remodeling by regulating miR-203a, which targets fosb. This process promotes the proliferation and differentiation of myoblast, thereby improving the quality of muscle.