Medical Physiology

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Browsing Medical Physiology by Subject "Adipocytes"

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    Factors that affect the adipocytic differentiation of adipose-derived mesenchymal stem cells
    (Stellenbosch : Stellenbosch University, 2022-04) McCaffrey, Caitlin; Ferris, William; Van Vuuren, Derick; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Medical Physiology.
    Background – Increased adiposity, particularly the accumulation of visceral adipose tissue is linked to the onset and progression of the metabolic syndrome. Despite the known pathogenicity of excessive visceral fat accrual, a paucity of knowledge on the mechanism behind its expansion exists. We hypothesise that hypertrophy and cellular dysfunction of subcutaneous adipocytes leads to the secretion of endocrine factors which stimulate adipogenesis in visceral adipose-derived mesenchymal stem cells (AD-MSCs) and that this communication might be affected by diet. We also postulate that the endocrine-induced adipogenesis of visceral AD-MSCs is amplified in individuals prescribed the PPARγ agonist, rosiglitazone for treatment of type II diabetes mellitus. Methods – Male Wistar rats at 3-weeks of age were fed either control lab chow, a high-fat diet (HFD), or an elevated sugar diet (ESD) (n = 7/group) ad libitum for 16 weeks and euthanised. The rat weights and endpoint fasting blood glucose were recorded and bilateral inguinal subcutaneous and retroperitoneal visceral adipose tissue depots excised. Histological studies of the tissue allowed adipocyte structure to be observed and measured. AD-MSCs from each depot were also isolated and expanded in vitro. The in vitro morphology of AD-MSCs was characterised, proliferation monitored, and the expression of the MSC markers (CD90+ and CD45-) measured. Adipogenesis was induced in the AD-MSCs, and conditioned media (CM) – containing the secretome of the mature adipocytes – was collected. Naïve AD-MSCs isolated from both adipose depots of age-matched control rats (n = 3) were then treated with the subcutaneous- and visceral conditioned media alone or in combination with either standard growth media (SGM) or adipocyte differentiation media (AM). This was repeated with and without the addition of 1μM rosiglitazone (Rosi). The effects of these treatments were qualitatively assessed by microscopy of oil red O-stained lipids and quantitatively assessed by in-silico micrograph- and spectrophotometric analyses. Results – The findings of this study indicate that feeding male Wistar rats a HFD or an ESD increases the mass of the inguinal and retroperitoneal adipose depots and cause hypertrophy in the constituent adipocytes. The diets also affected the MSC marker expression of the AD-MSCs from both adipose depots, having elevated the expression of CD90 in the HFD AD-MSCs but decreased the CD90 expression in the ESD AD-MSCs. The CM samples collected from the chow-fed control, HFD, and ESD adipocytes stimulated lipid accrual in the visceral AD-MSCs when added alone or in combination with SGM or AM, but the most significant adipogenic effects were induced by the ESD visceral CM in all three formulations. Only the control subcutaneous- and ESD visceral CM, when supplemented with AM, were able to elicit significant lipid accrual in the subcutaneous AD-MSCs. Following Rosi supplementation, the visceral AD-MSCs treated with HFD- and control CM treatments accumulated significant quantities of intracellular lipids. None of the CM+Rosi treatments stimulated significant lipid accrual in the naïve subcutaneous AD-MSCs. The CM and Rosi experiments revealed that subcutaneous AD-MSCs are less susceptible to CM-induced adipogenesis than visceral AD-MSCs. Conclusion – This study provides evidence for a possible endocrine communication between the subcutaneous and visceral adipose depots which appears to be amplified by the chronic consumption of an elevated sugar diet as well as by supplementation with rosiglitazone. These novel findings may contribute towards elucidating the underlying mechanisms behind the pathogenic expansion of visceral adipose tissue.