Advances in the Protective Effects and Mechanisms of β‐Aminoisobutyric Acid in Maintaining Multi‐Organ Homeostasis

ABSTRACT β‐Aminoisobutyric acid (BAIBA) is an exercise‐responsive myokine/metabolite released by skeletal muscle and has attracted increasing interest as a potential exercise mimetic and therapeutic candidate in preclinical research. BAIBA acts locally in skeletal muscle and can also reach distal organs through the circulation, contributing to the maintenance of multi‐organ metabolic homeostasis. In skeletal muscle, BAIBA may preferentially enhance slow‐twitch muscle adaptations and protect against muscle atrophy through metabolic signaling involving AMPK and PPARδ, while the precise contribution of PGC‐1α remains to be clarified. In the liver, BAIBA regulates glucose and lipid metabolism through pathways involving PPARα and AMPK, enhances fatty acid oxidation, reduces lipid accumulation, and attenuates liver injury. In adipose tissue, BAIBA promotes white adipose tissue browning and fatty acid oxidative metabolism and attenuates metabolic inflammation in preclinical models. In bone, L‐BAIBA suppresses osteoclastogenesis through SLC6A6‐related signaling, while BAIBA also promotes osteoprogenitor cell proliferation through ROS‐related mechanisms and synergizes with mechanical loading to enhance bone formation. In the heart, BAIBA enhances myocardial fatty acid oxidative metabolism through AMPK‐associated ACC/CPT1 signaling, supports myocardial energy metabolism, and attenuates post‐infarction heart failure in rodent models. Human observational studies have shown that circulating BAIBA levels are inversely associated with several cardiometabolic risk factors, while acute exercise can increase circulating BAIBA, although responses to longer‐term exercise vary across populations and interventions. This article systematically reviews the metabolic origin of BAIBA and its protective effects and molecular mechanisms in maintaining homeostasis in skeletal muscle, liver, adipose tissue, bone, and heart, with the aim of providing a reference for future mechanistic studies and translational intervention strategies.