Regulation and implications of adipocyte lipolysis in musculoskeletal tissues

Abstract The musculoskeletal (MSK) system contains several unique adipose tissue depots with an emerging role in health and disease. This includes bone marrow adipose tissues (BMAT), intramuscular and epimuscular adipose tissues (IMAT/EMAT), and adipose tissues in joints and around tendons. Adipocytes within these depots are differentially sensitive to lipolytic stimuli which provides clues as to how, and when, local lipolysis participates in MSK health and global metabolism. This review covers known mechanisms regulating lipolysis in each of the MSK adipose depots while emphasizing commonalities and exploring unique features and potential consequences. For each depot, we evaluate its known basal and stimulated lipolytic responses, particularly in response to adrenergic stimuli, caloric restriction, and exercise. We further synthesize findings across fields including endocrinology, cancer biology, food science, and exercise metabolism. Overall, this review emphasizes the broad importance of lipolysis in MSK adipocytes across species and conditions and highlights translational challenges and opportunities. We also highlight ongoing and future work toward understanding how the mechanisms and consequences of lipolysis in adipocytes of the MSK system can contribute to our ability to promote and maintain health throughout the lifespan.