Metabolic Differences between Subcutaneous and Visceral Adipocytes Differentiated with an Excess of Saturated and Monounsaturated Fatty Acids (original) (raw)
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in vitro ability to differentiate towards at least three cellular lineages: adipocytes, osteocytes, and chondrocytes. When considering the adipogenic potential of MSCs, 21 days after induction with specific media, these cells are capable of accumulating cytoplasmic lipid vacuoles, similar to native adipose tissue-isolated adipocytes. There is scarce data regarding the composition of fatty acids within the in vitro-differentiated adipocytes and the regulation of the metabolic functions. We used gas chromatography/mass spectrometry to identify fatty acid (FA) species in MSC-derived preadipocytes/adipocytes and compared them to the FA profile found in adipocytes isolated from normal-weight adult adipose tissue. We found that differentiation media did not contain essential fatty acids, and MSCs-differentiated preadipocytes and mature adipocytes contain significantly reduced amounts of arachidonic acid (C20:4) and docosahexaenoic acid (C22:6) compared to native adipose tissue. MSCs, adipocytic precursors and mature adipocytes lacked linolenic acid (C18:3) and contained almost insignificant amounts of linoleic acid (C18:2) compared to native adipose tissue-derived adipocytes. To investigate the gene expression-related causes in the dysregulation of lipid metabolic pathways, we compared gene expression profiles of undifferentiated MSCs, preadipocytes/adipocytes to the reference adipose tissue, and microarray analysis showed different expression profiles in genes along the adipocytic differentiation pathway, mainly in desaturase and elongases, genes involved in polyunsaturated fatty acids (PUFA) synthesis from essential fatty acids. The composition of FAs in adipocytic differentiation media, together with MSCs inability to functionally convert these acids into appropriate lipidic end-products required for normal functioning of mature adipocytes makes the MSCs poor candidates of in vitro adipogenesis process, while the differentiation media requires supplements of essential fatty acids, which may improve cellular function.
2012
Introduction-Obesity is a major risk factor for several musculoskeletal conditions that are characterized by an imbalance of tissue remodeling. Adult stem cells are closely associated with the remodeling and potential repair of several mesodermally derived tissues such as fat, bone, and cartilage. We hypothesized that obesity would alter the frequency, proliferation, multipotency, and immunophenotype of adult stem cells from a variety of tissues. Materials and Methods-Bone marrow-derived mesenchymal stem cells (MSCs), subcutaneous adipose-derived stem cells (sqASCs), and infrapatellar fat pad-derived stem cells (IFP cells) were isolated from lean and high-fat diet induced obese mice, and their cellular properties were examined. To test the hypothesis that changes in stem cell properties were due to the increased systemic levels of free fatty acids (FFAs), we further investigated the effects of FFAs on lean stem cells in vitro. Results-Obese mice showed a trend toward increased prevalence of MSCs and sqASCs in the stromal tissues. While no significant differences in cell proliferation were observed in vitro, the differentiation potential of all types of stem cells was altered by obesity. MSCs from obese mice demonstrated decreased adipogenic, osteogenic, and chondrogenic potential. Obese sqASCs and IFP cells showed increased adipogenic and osteogenic differentiation, but decreased chondrogenic ability. Obese MSCs also showed decreased CD105 and increased PDGFRα expression, consistent with decreased chondrogenic potential. FFA treatment of lean stem cells significantly altered their multipotency but did not completely recapitulate the properties of obese stem cells. Conclusions-These findings support the hypothesis that obesity alters the properties of adult stem cells in a manner that depends on the cell source. These effects may be regulated in part by increased levels of FFAs, but may involve other obesity-associated cytokines. These findings contribute to our understanding of mesenchymal tissue remodeling with obesity, as well as the development of autologous stem cell therapies for obese patients.
2020
Objective(s): Adipose tissue is one of the most important endocrine organs that liberates many metabolic mediators such as hormones, cytokines, and chemokines. Different types of fatty acids have key roles in adipogenesis. The aim of this study was to evaluate the effects of two essential fatty acids, including Arachidonic acid (AA) and Eicosapentaenoic acid (EPA), on the process of adipogenicity in human Adipose-Derived Stem Cells (hADSCs). Materials and Methods: After immunophenotyping of hADSCs by flowcytometry, they were differentiated into adipocytes and simultaneously exposed to 30 μM and 60 μM of AA and 25 μM and 50 μM of EPA. Further, along with the MTS assay, the activity of glycalaldehyde-3-phosphate dehydrogenase (GAPDH) was also measured. In addition, expression of lipid markers including peroxisome proliferator-activated receptor γ2 (PPARγ2) and glucose transporter 4 (GLUT4) was evaluated, and the neutral lipid contents were determined using Oil red O staining. Results:...
Open Journal of Endocrine and Metabolic Diseases, 2013
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 highfat 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.
Journal of Animal Physiology and Animal Nutrition
Adipose-derived stem cells (ADSCs) possess multipotent properties, and their proper functionality is essential for further development of metabolic disorders. In the current study, we explored the impact of two n-3 LC-PUFAs (long-chain polyunsaturated fatty acids, DHA-docosahexaenoic; C22:6, and EPA-eicosapentaenoic; C20:5) on a specific profile of lipolytic-related gene expressions in the in vitro-differentiated subcutaneous and visceral ADSCs from rabbits. The subcutaneous and visceral ADSCs were obtained from 28-day-old New Zealand rabbits. The primary cells were cultured up to passage 4 and were induced for adipogenic differentiation. Thereafter, the differentiated cells were treated with 100 µg EPA or DHA for 48 hr. The total mRNA was isolated and target genes expression evaluated by real-time RCR. The results demonstrated that treatment of rabbit ADSCs with n-3 PUFAs significantly enhanced mRNA expression of Perilipin A, while the upregulation of leptin and Rab18 genes was seen mainly in ADSCs from visceral adipose tissue. Moreover, the EPA significantly enhanced PEDF (Pigment Derived Epithelium Factor) mRNA expression only in visceral cells. Collectively, the results suggest activation of an additional lipolysis pathway most evident in visceral cells. The data obtained in our study indicate that in vitro EPA up-regulates the mRNA expression of the studied lipolysis-associated genes stronger than DHA mainly in visceral rabbit ADSCs.
Secreted factors from adipose tissue increase adipogenic differentiation of mesenchymal stem cells
Objectives: Adipose tissue engineering is one of the hottest topics in the field of regenerative medicine. Fat tissue has been considered as an abundant and accessible source of adult stem cells by tissue engineers, since it gives rise to adipose stem cells. However, recent reports have pointed out that adipose tissue, as a secretory and endocrine organ, might secrete cytokines that regulate body functions such as metabolism, infammation and more. In this study, we aim to investigate the adipogenicinducing factors secreted by fat tissue. Materials and methods: Conditioned medium were collected by culturing fat tissue fragments in plastic flasks. Mesenchymal stem cells (MSCs) cultured in conditioned medium (CM) to test the adipogenicinducing factors. Oil red O staining, reverse transcription/polymerase chain reaction and immunocytofluorescent staining were performed to examine the differentiation of MSCs in CM. Results: MSCs cultured in CM of adipose tissue spontaneously differentiated into adipocytes. Furthermore, supplementation of insulin or dexamethasone to CM accelerated the process of lipid accumulation of differentiated MSCs. Discussion: Results from this study demonstrated that fat tissues secrete small molecules, which induce adipogenic differentiation of MSCs. Conclusions: Our study provides clues for improving adipose tissue engineering by using fragmented adipose tissue as sources of fat-inducing factors.
Functional characterization of human mesenchymal stem cell-derived adipocytes
Biochemical and Biophysical Research Communications, 2003
The function of adipocytes derived from human mesenchymal stem cells (hMSC) was investigated for the first time in hMSC from fetal liver (FL) and adult bone marrow (BM) and compared with preadipocytes from human subcutaneous adipose tissue differentiated according to adipocyte-specific protocols. FL-and BM-derived adipocytes displayed both morphological and functional characteristics of mature adipocytes including specific intracellular signaling pathways for tumor necrosis factor-a, catecholamine-regulated lipolysis as well as secretion of adiponectin and leptin. Similar to differentiated preadipocytes, hMSC adipocytes displayed lipolytic effects mediated by b-adrenoceptors and antilipolytic effects mediated by the a2A-adrenoceptor (a2A-AR) and expressed proteins with a pivotal role in human lipolysis, including b2-AR, a2A-AR, and hormone-sensitive lipase. We conclude that hMSC-derived adipocytes are morphologically and functionally similar to preadipocytes and display an intact lipolytic signaling pathway and endocrine function. These systems could be of great value in adipocyte research as a renewable source of adipocytes.
Journal of Food Biochemistry, 2018
Obesity is a metabolic disorder that manifests into various forms. Recent studies have indicated that the pomegranate (Punica granatum) seed oil (PSO) has many biologically active components that help in controlling diet-induced obesity and insulin resistance. However, its impact on the adipogenic differentiation of human adiposederived mesenchymal stem cells (HADMSC) remains unclear. Here we have attempted to study the anti-obesity potential of SHAMstat3pg, a fatty acid composite extracted from PSO. It is composed of three dietary fatty acids: punicic acid [(9Z,11E,13Z)-9,11,13-Octadecatrienoic acid], oleic acid [Cis-9-Octadecenoic acid], and linoleic acid [(9Z,12Z)-octadeca-9,12-dienoic acid]. In this study, we discuss the impact of the fatty acids on adipogenesis, inflammation, glucose uptake, and mitochondrial ATP production. The impact of SHAMstat3pg on the expression of various obesity-associated protein and mRNA transcripts in HADMSC was also analyzed. The results indicate that exposure to 10 µg/ml of SHAMstat3pg (24 hr) inhibited adipogenesis of HADMSC, ameliorated inflammation, attenuated ATP production, and glucose uptake. Also, the extract favorably regulated the mRNA expression of the studied obesity-associated gene transcripts. Practical applications SHAMstat3pg has the potential to serve as a multi-targeted therapy for the management of obesity. This study demonstrated that the dietary fatty acids inhibited the differentiation of preadipocytes to adipocytes. SHAMstat3pg has also shown to have a favorable impact on the expression of the obesity-linked proteins and genes in HADMSC that are associated with adipogenesis, inflammation, satiety, energy intake/expenditure (central and peripheral signaling molecules). The study gives an overview of the vast number of genes impacted by the treatment with SHAMstat3pg paving the way for future studies to demonstrate the exact mode of action of how dietary fatty acids can help manage obesity, insulin resistance, and type 2 diabetes.