Diet-Induced Obesity in Stem Cell Antigen-1 KO Mice

Abstract

Stem Cell Antigen-1 (Sca-1) is a member of the lymphocyte-activated protein 6 family and has served as a marker for the identification of stem cells in various tissues, including fat depots. In vitro and in vivo studies suggest the possible involvement of Sca-1 in adipogenic differentiation and link Sca-1 antigenicity with adipocyte progenitors. Previously, we showed that Sca-1-enriched populations of ear mesenchymal stem cells possess enhanced capacity to differentiate into adipocytes. Additionally, we determined the natural frequency and localization of Sca-1-positive progenitor/stem cells in brown and white fat in situ. The present study addressed the question whether Sca-1 deficiency alters the white adipose tissue response to a high-saturated-fat diet. Our results show that Sca-1 null mice (Sca-1 -/-) fed high-fat diet developed obesity equally well as wildtype mice, suggesting either an indirect in vivo effect of Sca-1 or a compensatory response to Sca-1 deficiency. However, contrary to wild-type mice, high fat diet-fed Sca-1 -/-mice showed no alterations in serum adipocytokines. The data lead to the conclusion that Sca-1 is either redundant or a nonessential marker of adipose progenitor/stem cells. Nevertheless, since Sca-1-deficient mice displayed elevated blood glucose at fasting and exhibited glucose intolerance and insulin resistance, Sca-1 has subtle effects on adipose function. Thus, the Sca-1-deficient mice may provide a useful model for metabolic studies.

Fat depot-specific gene signature and ECM remodeling of Sca1high adipose-derived stem cells

“…Sca1 (Ly6a) is highly expressed in pro-adipogenic mesenchymal stem cells (Staszkiewicz et al, 2008); however, the gene targeting of Sca1 in mice did not cause a significant change in adipose tissue size (Staszkiewicz et al, 2012). These findings suggest that Sca1 serves as a useful cell surface marker to identify pro-adipogenic ASCs; however, Sca1 itself may not play a substantial biological role in the regulation of adipose tissue size and function.…”

Zfp423 Expression Identifies Committed Preadipocytes and Localizes to Adipose Endothelial and Perivascular Cells

“…Most notably, Friedman and colleagues pioneered an elegant cell sorting strategy to identify and isolate a rare, but highly adipogenic progenitor population capable of differentiating into functional adipocytes both in vitro and in vivo (Rodeheffer et al, 2008). However, the markers utilized (Sca-1, CD24 and CD34) are not individually specific for the adipose lineage, and some are functionally dispensible for the initial formation of adipose progenitors (Staszkiewicz et al, 2011). In addition, the molecular identity and gene expression program of primary committed preadipocytes from different depots remain incompletely understood.…”

Recruitment of fat cell precursors during high fat diet in C57BL/6J mice is fat depot specific

“…Flow cytometry analysis has revealed that the stem cell/precursor cell population in the SVF of mice fat depots is Sca-1 positive [ 10 , 14 ]. Our previous in vitro studies showed that Sca-1 positive cells isolated/sorted from either ear mesenchymal stem cells (EMSC) or SVF of fat depots displayed robust adipogenic potential [ 16 , 17 ]. In contrast, our in vivo experiments showed only subtle metabolic disorders (glucose intolerance, insulin resistance) between Sca-1 KO and wild type mice [ 17 ].…”

“…Our previous in vitro studies showed that Sca-1 positive cells isolated/sorted from either ear mesenchymal stem cells (EMSC) or SVF of fat depots displayed robust adipogenic potential [ 16 , 17 ]. In contrast, our in vivo experiments showed only subtle metabolic disorders (glucose intolerance, insulin resistance) between Sca-1 KO and wild type mice [ 17 ]. We did not detect either a defect in adipogenic tissue development or an increase in fat mass content between Sca-1 KO and wild type mice in an obesogenic environment.…”

“…We did not detect either a defect in adipogenic tissue development or an increase in fat mass content between Sca-1 KO and wild type mice in an obesogenic environment. We proposed that the lack of an in vivo phenotype may be explained by compensatory mechanisms that do not operate under in vitro conditions [ 17 , 2 ]. Although the precise function of Sca-1 is currently unknown, changes in the population of Sca-1 positive cells were detected in the in vivo model.…”