Abstract
Spermatogenesis‐associated protein 4 (SPATA4) is conserved across multiple species. However, the function of this gene remains largely unknown. In this study, we generated Spata4 transgenic mice to explore tissue‐specific function of SPATA4. Spata4 overexpression mice displayed increased subcutaneous fat tissue compared with wild‐type littermates at an old age, while this difference was not observed in younger mice. Aging‐induced ectopic fat distribution, inflammation, and insulin resistance were also significantly attenuated by SPATA4. In vitro, SPATA4 promoted preadipocyte differentiation through activation of the ERK1/2 and C/EBPβ pathway and increased the expression of adipokines. These data suggest SPATA4 can regulate lipid accumulation in a tissue‐specific manner and improve aging‐induced dysmetabolic syndromes. Clarifying the mechanism of SPATA4 functioning in lipid metabolism might provide novel therapeutic targets for disease interventions.
Highlights
Fat redistribution, wherein fat tissue transfers from subcutaneous depots to visceral depots, such as liver, muscle, and heart, occurs commonly in aging individuals
We have previously reported that Spermatogenesis-associated protein 4 (SPATA4) contains a calponin homology (CH) domain at the N-terminus, and is negatively modulated by regulatory factor X1 (RFX1) (Jiang et al, 2013)
hematoxylin and eosin (H&E) staining showed more lipid droplet accumulation in liver and brown adipose tissue (BAT) tissues of WT aged mice compared with the young mice, and these aging-induced changes were significantly attenuated in transgenic mice (TG) old mice (Figure 2a,b, Figure S2a,b)
Summary
Wherein fat tissue transfers from subcutaneous depots to visceral depots, such as liver, muscle, and heart, occurs commonly in aging individuals This phenomenon is associated with increased risk of the dysmetabolic syndromes, such as diabetes, hypertension, and hyperlipidemia, as well as various other aging-related diseases (Palmer & Kirkland, 2016; Pararasa et al, 2015). SPATA4 promotes osteoblast differentiation through the ERKactivated RunX2 pathway (Wang et al, 2011) and protects Hela cells from etoposide-induced apoptosis through the mitochondrial apoptotic pathway (Jiang et al, 2015). We did not observe any significant phenotypical changes in reproductivity, appearance, and metabolism in Spata knock out mice These results unveil a role of SPATA4 in adipocyte differentiation and fat tissue distribution. Clarification of the mechanisms by which SPATA4 regulates fat metabolism would be beneficial to our understanding of how aging and obesity affect the development of dysmetabolic syndrome
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