Abstract
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.
Highlights
Population aging and the increasing incidence of obesity in recent years have been serious concerns worldwide [1,2,3]
We focus on the important role of AMPK and PGC-1α signaling for autophagy activity
This study revealed that AMPK activation can reduce lipid accumulation in the liver and protect the liver from inflammation and fibrosis
Summary
Population aging and the increasing incidence of obesity in recent years have been serious concerns worldwide [1,2,3]. Increased adipose tissue during aging leads to the production of adipo-cytokines (adipokines) such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which induce low grade chronic inflammation [15] This condition is referred to as “inflammaging” and “metaflammation”, the pathological concept important in the vicious cycle of aging and obesity. Adiponectin, one of the major adipokines, plays a significant role in energy homeostasis and the insulin signaling pathway It improves fatty acid oxidation in skeletal muscle by increasing AMPK phosphorylation and increases mitochondrial oxidative metabolism and biogenesis [55,56]. FGF21, secreted from the liver, has a direct effect on glucose homeostasis, lipid metabolism, and insulin sensitivity in skeletal muscle [62,63] It stimulates PGC-1α function and AMPK signaling pathways by several direct and indirect ways [64]. Dysregulated Autophagy Aggravates Sarcopenic Obesity through Dysfunctional AMPK and PGC-1α Signaling Pathway-Mediated Inflammation and Insulin Resistance
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