Vaspin promotes insulin sensitivity in elderly muscle and is upregulated in obesity

Abstract

Adipokines have emerged as central mediators of insulin sensitivity and metabolism, in part due to the known association of obesity with metabolic syndrome disorders such as type 2 diabetes. Recent studies in rodents have identified the novel adipokine vaspin as playing a protective role in inflammatory metabolic diseases by functioning as a promoter of insulin sensitivity during metabolic stress. However, at present the skeletal muscle and adipose tissue expression of vaspin in humans is poorly characterised. Furthermore, the functional role of vaspin in skeletal muscle insulin sensitivity has not been studied. Since skeletal muscle is the major tissue for insulin-stimulated glucose uptake, understanding the functional role of vaspin in human muscle insulin signalling is critical in determining its role in glucose homeostasis. The objective of this study was to profile the skeletal muscle and subcutaneous adipose tissue expression of vaspin in humans of varying adiposity, and to determine the functional role of vaspin in mediating insulin signalling and glucose uptake in human skeletal muscle. Our data shows that vaspin is secreted from both human subcutaneous adipose tissue and skeletal muscle, and is more highly expressed in obese older individuals compared to lean older individuals. Furthermore, we demonstrate that vaspin induces activation of the PI3K/AKT axis, independent of insulin receptor activation, promotes GLUT4 expression and translocation and sensitises older obese human skeletal muscle to insulin-mediated glucose uptake.

Circulating Adipokine VASPIN Is Associated with Serum Lipid Profiles in Humans

“…A second potential pathway was described by Jung et al, who propose a model in which VASPIN acts via the PI3 kinase/AKT pathway and ameliorates atherosclerosis (Jung et al, 2011;Liu et al, 2018). This finding was further supported by the analysis of Nicholson et al, showing an induction of the PI3 kinase/AKT axis by VASPIN and thereby promoting GLUT4 expression and translocation (Nicholson et al, 2019). Finally, murine VASPIN may also counteract endoplasmic reticulum (ER) stress in obesity by serving as a ligand for the cellsurface GRP78/MTJ-1 complex .…”

Circulating Levels of Visceral Adipose Tissue-Derived Serine Protease Inhibitor (Vaspin) Appear as a Marker of Musculoskeletal Pain Disability

“…Animal studies demonstrated that vaspin can reduce body weight, improve the whole-body metabolic status, enhance bone strength and trabecular bone mass in obesity [ 29 ], promote osteogenesis [ 29 ], and prevent osteoclastogenesis [ 47 ]. Moreover, vaspin is produced by skeletal muscle and was shown to prevent insulin resistance in human myotubes [ 28 ]. These findings clearly indicate vaspin involvement in bone and muscle physiology.…”

“…However, this conclusion was drawn from the single study testing a relatively small sample of both affected and control individuals ( n = 62). A newly discovered adipokine, visceral adipose tissue-derived serine protease inhibitor (vaspin, SERPINA12) was found to be associated with obesity in human subjects [ 25 , 26 , 27 , 28 ]. Moreover, vaspin is produced by skeletal muscle, and apparently is involved in bone metabolism in an obesity-dependent manner [ 28 , 29 ].…”

Involvements of long noncoding RNAs in obesity‐associated inflammatory diseases

“…Indeed, it has been shown that obese, but not normal‐weight, subcutaneous AT secretome impairs the myogenesis of old myoblasts 69 . Also, AT in older individuals with increased adiposity secretes differential amounts of adipokines that can impact the metabolic health and insulin sensitivity of older skeletal muscle tissue 70 . Furthermore, circulatory levels of TNFα and IL‐6 have been shown to be negatively correlated to muscle mass and strength in older individuals, 71 and their muscle atrophic actions have been demonstrated in both in vitro and in vivo studies 72,73 .…”