Role of adipokines in sarcopenia.

ABSTRACT: Sarcopenia is an age-related disease that mainly involves decreases in muscle mass, muscle strength and muscle function. At the same time, the body fat content increases with aging, especially the visceral fat content. Adipose tissue is an endocrine organ that secretes biologically active factors called adipokines, which act on local and distant tissues. Studies have revealed that some adipokines exert regulatory effects on muscle, such as higher serum leptin levels causing a decrease in muscle function and adiponectin inhibits the transcriptional activity of Forkhead box O3 (FoxO3) by activating peroxisome proliferators-activated receptor-γ coactivator -1α (PGC-1α) and sensitizing cells to insulin, thereby repressing atrophy-related genes (atrogin-1 and muscle RING finger 1 [MuRF1]) to prevent the loss of muscle mass. Here, we describe the effects on muscle of adipokines produced by adipose tissue, such as leptin, adiponectin, resistin, mucin and lipocalin-2, and discuss the importance of these adipokines for understanding the development of sarcopenia.

The p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop mediates vasoactive intestinal peptide effects on osteoarthritis chondrocytes.

Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA). Targeting inflammatory pathways is an important therapeutic strategy for OA. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide with potent anti-inflammatory effects; however, its role and mechanism in OA remain unclear. In this study, microarray expression profiling from the Gene Expression Omnibus database and integrative bioinformatics analyses were performed to identify differentially expressed lncRNAs in OA samples. qRT-PCR validation of the top ten different expressed lncRNAs indicated that the expression level of intergenic non-protein coding RNA 2203 (LINC02203, also named LOC727924) was the highest in OA cartilage compared to normal cartilage. Hence, the LOC727924 function was further investigated. LOC727924 was upregulated in OA chondrocytes, with a dominant sub-localization in the cytoplasm. In OA chondrocytes, LOC727924 knockdown boosted cell viability, suppressed cell apoptosis, reactive oxygen species (ROS) accumulation, increased aggrecan and collagen II, decreased matrix metallopeptidase (MMP)-3/13 and ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4/5 levels, and reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). LOC727924 could interact with the microRNA 26a (miR-26a)/ karyopherin subunit alpha 3 (KPNA3) axis by competitively targeting miR-26a for KPNA3 binding, therefore down-regulating miR-26a and upregulating KPNA3; in OA chondrocytes, miR-26a inhibition partially abolished LOC727924 knockdown effects on chondrocytes. miR-26a inhibited the nuclear translocation of p65 through targeting KPNA3 and p65 transcriptionally activated LOC727924, forming a p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop to modulate OA chondrocyte phenotypes. In vitro, VIP improved OA chondrocyte proliferation and functions, down-regulated LOC727924, KPNA3, and p65 expression, and upregulated miR-26a expression; in vivo, VIP ameliorated destabilization of the medial meniscus (DMM)-induced damages on the mouse knee joint, down-regulated KPNA3, inhibited the nuclear translocation of p65. In conclusion, the p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop modulates OA chondrocyte apoptosis, ROS accumulation, extracellular matrix (ECM) deposition, and inflammatory response in vitro and OA development in vivo, being one of the mechanisms mediating VIP ameliorating OA.

Inflammation and sarcopenia: A focus on circulating inflammatory cytokines.

Sarcopenia is an aged-related syndrome that is progressive and can be accelerated by other concomitant disease states. Sarcopenia, characterized by loss of skeletal muscle mass, reduced muscle strength, and/or reduced physical performance, is one of the main reasons for limitation of daily activities in the elderly. It is associated with an increased incidence of many adverse events, such as dysfunction, falls, weakness, hospitalization, disability and even death. Sarcopenia justifies one of the most widely accepted theories that low-grade chronic inflammation associated with aging, known as inflammatory aging, is important to the pathogenesis of many age-related diseases. Currently, the diagnosis of sarcopenia is based on a comprehensive assessment of three aspects: muscle mass, muscle strength and physical performance. The measurement of muscle mass is complicated, as the measurement of muscle strength and gait speed is easily affected by the physical conditions of the subjects. This makes the measurements inaccurate and prospective, and it is difficult to achieve continuous, purposeful monitoring. In addition, serum levels of inflammatory cytokines change as inflammatory states develop in the elderly population. This manuscript focuses on the correlation between serum inflammatory cytokines and sarcopenia in recent years, plus the possible underlying mechanisms.