High-Fat Diets-Induced Metabolic Alterations Alter the Differentiation Potential of Adipose Tissue-Derived Stem Cells

Background: Adipose tissue-derived stem cells (ASC) possess the ability to differentiate into adipocytes or endothelial cells to help in the adipogenesis, vasculogenesis and vascular repair. This study aims at determining the impact of high-fat diets (HFD)-induced type 2 diabetes (T2D) on the differentiation potential of ASC. Results: C57BL/6J male mice were fed a vegetal (VD) or an animal (AD) HFD. Isolation of ACS from mice showing different levels of metabolic alterations reveals that advanced T2D did not affect the number of cells per gram of tissue. Rather, a higher proportion of inflammatory CD36+ cells was identified in HFD fed mice. Despite a marked decreased expression of adipogenic genes (aP2, C/EBPα and PPARγ2), ASC from HFD groups had a higher adipogenic potential and a lower endothelial differentiation potential in vitro compared to control. ASC from the VD group had enhanced cyclin B1 expression and had more adipogenic potential compared to AD group. Conclusion: Our results demonstrate that the metabolic modifications, linked to the nature of fatty acids in diets, modulate the differentiation potential of ASC with increased adipogenesis to the detriment of the endothelial pathway. Results highlight the importance of evaluating the ASC differentiation behavior in a context of autologous cell-based therapy for the repair of vascular tissues in diabetic patients.

Adipocytes modulate vascular smooth muscle cells migration potential through their secretions

Impairment of vascular smooth muscle cells (VSMC) is recognized as a predisposition factor for atherosclerosis development. We hypothesize that the metabolic syndrome has a direct impact on VSMC migration and phenotypic switching, which may increase the incidence of atherosclerotic events. Aortic VSMC were extracted from 10 weeks old C57BL6 mice and incubated for 24 hr in adipocytes conditioned cell culture medium. Adipocytes were extracted from diabetic C57BL6 male mice fed with either a vegetal or an animal High-Fat-Diet (HFD) for 20 weeks. Migration of VSMC in response to conditioned media stimulations was significantly modulated compared to control. The most extended effects on VSMC were triggered by adipocytes from mice fed with animal HFD. These effects were concurrent with increased leptin concentrations and decreased adiponectin levels in conditioned media. A significant up-regulation of CD36 mRNA level was found in VSMC treated with adipocytes from HFD-fed mice. In conclusion, we have shown that the development of adipocyte-induced VSMC alterations is linked to diet fatty acid composition and the degree of metabolic alterations. The modulation of adipokine secretions in the adipose tissue that is linked to metabolic alterations may alter the physiology of VSMC and thus accelerate the development of metabolic-related vascular diseases.