Abstract
IntroductionObesity, which is excessive expansion of white adipose tissue, is a major risk factor for several serious health issues, including diabetes, cardiovascular disease and cancer. Efforts to combat obesity and related diseases require understanding the basic biology of adipogenesis. However, in vitro studies do not result in lipid composition and morphology that are typically seen in vivo, likely because the in vitro conditions are not truly representative of in vivo adipose tissue formation. In vitro, low oxygen tension and cytoskeletal tension have been shown to independently regulate adipogenesis, but in vivo, these two factors simultaneously influence differentiation.MethodsThe purpose of our study was to examine the influence of physiological oxygen tension on cytoskeletal tension-mediated adipogenesis. Adipose-derived stem cells (ASCs) were differentiated under both ambient (20%) and physiological (5%) oxygen conditions and treated with cytoskeletal inhibitors, cytochalasin D or blebbistatin. Adipogenesis was assessed on the basis of gene expression and adipocyte metabolic function.ResultsAdipose tissue metabolic markers (glycerol-3-phosphate dehydrogenase (GPDH) and triglycerides) were significantly down-regulated by physiological oxygen levels. Reducing cytoskeletal tension through the use of chemical inhibitors, either cytochalasin D or blebbistatin, resulted in an up-regulation of adipogenic gene expression (peroxisome proliferator-activated receptor γ (PPARγ), lipoprotein lipase (LPL) and fatty acid binding protein 4 (FABP4)) and metabolic markers, regardless of oxygen levels. Cytochalasin D and blebbistatin treatment altered cytoskeletal organization and associated tension via different mechanisms; however, both conditions had similar effects on adipogenesis, suggesting that physiological oxygen-mediated regulation of adipogenesis in ASCs is modulated, in part, by cytoskeletal tension.ConclusionsThese results demonstrated that interactions between the cytoskeleton and oxygen tension influence adipogenic differentiation of ASCs.
Highlights
Obesity, which is excessive expansion of white adipose tissue, is a major risk factor for several serious health issues, including diabetes, cardiovascular disease and cancer
Cytochalasin D and blebbistatin treatment altered cytoskeletal organization and associated tension via different mechanisms; both conditions had similar effects on adipogenesis, suggesting that physiological oxygen-mediated regulation of adipogenesis in Adipose-derived stem cell (ASC) is modulated, in part, by cytoskeletal tension. These results demonstrated that interactions between the cytoskeleton and oxygen tension influence adipogenic differentiation of ASCs
ASCs treated with blebbistatin were incapable of maintaining a spread cell morphology, presumably because crosslinking between non-muscle myosin II and actin filaments was inhibited
Summary
Obesity, which is excessive expansion of white adipose tissue, is a major risk factor for several serious health issues, including diabetes, cardiovascular disease and cancer. In vitro evidence suggest that this shape change occurs early in the differentiation process and prior to the up-regulation of many adipocyte specific genes as well as independently of triglyceride accumulation [12], though the cause and mechanism for the morphological shift from fibroblastic to spherical in vivo have yet to be determined. These morphological changes are accompanied by cytoskeletal changes, including decreased actin synthesis [8] and reorganization [13]. Though cytoskeletal changes appear to be critical to the differentiation process, the detailed mechanisms driving the morphological shift are not yet understood
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