Abstract 413: CD34+CD31+ Endothelial Cells From Human Obese Subcutaneous but Not Omental Fat Show Adipogenic Potential
| Autor: | Anca D. Dobrian, Ashley James, Bronson A. Haynes |
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| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 36 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | In obesity, excess lipid storage and reduced adipogenesis causes adipocytes to undergo hypertrophy leading to inflammation and insulin resistance. Increasing adipogenic potential may reduce lipid overload and ectopic lipid accumulation. In mice, the vascular niche is a source of adipocyte progenitors and a subset of endothelial cells (ECs) can trans-differentiate to functional adipocytes. It is unknown if a similar process occurs in humans. Our hypothesis is that pro-inflammatory cytokines contribute to de-differentiation and support induction of a pro-adipogenic program in a subset of CD31+CD34+ EC in human fat. The aim of this study is to determine if CD34+ CD31+ ECs isolated from human obese fat can be trans-differentiated to adipocytes and if this process is depot-specific. CD31+CD34+ ECs isolated from subcutaneous (SC) or omental (OM) fat of obese subjects undergoing bariatric surgery (BAMVECs) were treated with 2.5ng/mL of IFNγ and TNFα for 24 hrs then cultured in adipocyte induction medium (AIM), containing insulin and rosiglitazone, for up to 21 days. Cells without cytokine treatment and/or grown in media without induction were used as controls. Lipid accumulation was quantified with AdipoRed. OM BAMVECs showed no lipid accumulation in AIM alone (RFU ratio 1.1 vs control) nor with prior cytokine treatment (RFU ratio 1.6 vs control). However, SC BAMVECs showed lipid accumulation in AIM alone (RFU ratio 2.7 vs control) and with a trend to increased lipid accumulation with prior cytokine treatment (RFU ratio 4.1 vs control). By RT-PCR, SC BAMVECs pre-treated with cytokines had a 6-fold increase in pre-adipocyte commitment marker zfp423 and a 106,000 increase in adiponectin vs controls. The increases vs controls in AIM alone were 2.6x for zfp423 and 21,700x for adiponectin. We conclude that SC but not OM BAMVECs can trans-differentiate to adipocytes as shown by lipid droplet accumulation and increased expression of adipocyte markers. Cytokine stimulation trended to increase EC plasticity. This indicates that CD34+ CD31+ ECs within the SC depot, when stimulated, may play a protective role by supplementing the adipocyte pools thus increasing growth and function of adipose tissue and potentially reducing ectopic fat storage. |
| Databáze: | OpenAIRE |
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