Dysregulated Autophagy Mediates Sarcopenic Obesity and Its Complications via AMPK and PGC1α Signaling Pathways: Potential Involvement of Gut Dysbiosis as a Pathological Link

International Journal of Molecular Sciences

HyungMuk Choi¹  KyoungSoo Kim¹  JiYeon Ryu¹  Hyung-In Yang² 

[1] Department of Clinical Pharmacology and Therapeutics, Kyung Hee University School of Medicine, Seoul 02447, Korea;East-West Bone & Joint Disease Research Institute, Kyung Hee University Hospital at Gangdong, Gandong-gu, Seoul 05278, Korea;

关键词: sarcopenic obesity;    AMPK signaling pathway;    PGC-1α signaling pathway;    aging;    insulin resistance;    inflammation;   

DOI  :  10.3390/ijms21186887

来源: DOAJ

【 摘 要 】

Sarcopenic obesity (SOB), which is closely related to being elderly as a feature of aging, is recently gaining attention because it is associated with many other age-related diseases that present as altered intercellular communication, dysregulated nutrient sensing, and mitochondrial dysfunction. Along with insulin resistance and inflammation as the core pathogenesis of SOB, autophagy has recently gained attention as a significant mechanism of muscle aging in SOB. Known as important cellular metabolic regulators, the AMP-activated protein kinase (AMPK) and the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) signaling pathways play an important role in autophagy, inflammation, and insulin resistance, as well as mutual communication between skeletal muscle, adipose tissue, and the liver. Furthermore, AMPK and PGC-1α signaling pathways are implicated in the gut microbiome–muscle axis. In this review, we describe the pathological link between SOB and its associated complications such as metabolic, cardiovascular, and liver disease, falls and fractures, osteoarthritis, pulmonary disease, and mental health via dysregulated autophagy controlled by AMPK and/or PGC-1α signaling pathways. Here, we propose potential treatments for SOB by modulating autophagy activity and gut dysbiosis based on plausible pathological links.

【 授权许可】

Unknown