Dataset Information

Paracrine Signaling in Visceral Fat

ABSTRACT: Accumulation of visceral (VIS) as opposed to subcutaneous (SUB) fat is a predictor of metabolic disorders, insulin resistance, and cardiovascular disease. This is due in part to the limited capacity of VIS fat to buffer lipids allowing them to deposit in insulin-sensitive tissues, thus impairing insulin action. In addition, VIS adipose tissue is more prone to fibrosis and inflammation, which in turn contributes to the pathogenesis of metabolic disease. Mechanisms underlying selective hypertrophic growth and tissue remodeling properties of VIS fat are not well understood. We and others identified subsets of adipose progenitors (APs) unique to VIS fat with differential adipogenic capacity. We named these CD34+ APs VIS low and VIS high based on low or high CD34 expression respectively. Despite sharing the same developmental origin, VIS low APs are adipogenic whereas VIS high APs are not. Furthermore, VIS high APs inhibit adipogenic differentiation of SUB and VIS low APs in vitro through the secretion of soluble inhibitory factor(s) including insulin-like growth factor binding protein 2 (Igfbp2). The number of VIS high APs increased with VIS adipose tissue expansion and their abundance in vivo causes hypertrophic growth, fibrosis, inflammation and impaired glucose and insulin tolerance. This study unveil the presence of APs unique to VIS fat involved in the paracrine regulation of adipogenesis and tissue remodeling.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Serum

SUBMITTER: Anna Bakhtina

LAB HEAD: Sarah Franklin

PROVIDER: PXD014672 | Pride | 2024-05-21

REPOSITORIES: Pride

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Publications

Identification of a Paracrine Signaling Mechanism Linking CD34<sup>high</sup> Progenitors to the Regulation of Visceral Fat Expansion and Remodeling.

Buffolo Márcio M Pires Karla Maria KM Ferhat Maroua M Ilkun Olesya O Makaju Aman A Achenbach Alan A Bowman Faith F Atkinson Donald L DL Holland William L WL Amri Ez-Zoubir EZ Chaurasia Bhagirath B Franklin Sarah S Boudina Sihem S

Cell reports 20191001 2

Accumulation of visceral (VIS) is a predictor of metabolic disorders and insulin resistance. This is due in part to the limited capacity of VIS fat to buffer lipids allowing them to deposit in insulin-sensitive tissues. Mechanisms underlying selective hypertrophic growth and tissue remodeling properties of VIS fat are not well understood. We identified subsets of adipose progenitors (APs) unique to VIS fat with differential Cd34 expression and adipogenic capacity. VIS low (Cd34 low) APs are adip ...[more]

PMID: 31597091

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Project description:Visfatin (VIS) is a hormone belonging to the adipokines’ group secreted mainly by the adipose tissue. VIS plays a crucial role in the control of energy homeostasis, inflammation, cell differentiation, and angiogenesis. VIS expression was confirmed in the hypothalamic-pituitary-gonadal (HPG) axis structures, as well as in the uterus, placenta, and conceptuses. We assumed that VIS may affect the abundance of proteins involved in the regulation of key processes occurring in the corpus luteum (CL) during the implantation process. In the present study, we performed the high-throughput proteomic analysis (liquid chromatography with tandem mass spectrometry, LC-MS/MS) to examine the influence of VIS (100 ng/mL) on differentially regulated proteins (DRPs) in the porcine luteal cells (LCs) on days 15-16 of pregnancy (implantation period). We have identified 511 DRPs, 276 of them were up-regulated and 235 down-regulated in the presence of VIS. Revealed DRPs were assigned to 162 gene ontology terms. Western blot analysis of five chosen DRPs, ADAM metallopeptidase with thrombospondin type 1 motif 1 (ADAMTS1), lanosterol 14-α demethylase (CYP51A1), inhibin subunit beta A (INHBA), notch receptor 3 (NOTCH3), and prostaglandin E synthase 2 (mPGES2) confirmed the veracity and accuracy of LC-MS/MS method. We indicated that VIS modulates the expression of proteins connected with the regulation of lipogenesis and cholesterologenesis, and, in consequence, may be involved in the synthesis of steroid hormones, as well as prostaglandins’ metabolism. VIS also changes the expression of proteins involved in the insulin signalling pathway. Moreover, we revealed that VIS affects the abundance of protein associated with ovarian cell proliferation, differentiation, and apoptosis, as well as CL new vessel formation and tissue remodelling. Our results seem to confirm the hypothesis concerning the important role of VIS in the regulation of ovarian functions during the peri-implantation period.

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