Department of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, San Antonio, TX, 78249, USA; UTSA-UTHSCSA Joint Graduate Program in Biomedical Engineering, San Antonio, TX, USA.
Department of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, San Antonio, TX, 78249, USA.
Biochem Biophys Res Commun. 2020 May 21;526(1):21-28. doi: 10.1016/j.bbrc.2020.03.025. Epub 2020 Mar 17.
The development of ectopic adipose tissue in skeletal muscle is associated with several skeletal muscle and metabolic pathologies, including Type II Diabetes Mellitus. The adipogenic differentiation of muscle precursor cells (MPCs) has been postulated to occur in skeletal muscle in vivo in a three-dimensional (3-D) configuration; therefore, it is appropriate to investigate this phenomenon using 3-D matrices in vitro. The capacity for MPC adipogenic differentiation in a 3-D environment was investigated in fibrin hydrogels by treating MPCs derived from healthy or diabetic animals with adipogenic induction medias that differed in their ability to increase lipid accumulation and activate the expression of genes associated with adipogenic differentiation (peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), and fatty acid synthase (FAS)). The capacity for adipogenic differentiation was diminished, but not prevented, if myogenic differentiation preceded MPC exposure to adipogenic induction conditions. Conversely, adipogenic differentiation was greater in hydrogels containing MPCs from diabetic rats as compared to those derived from lean rats, as evidenced by an increase in lipid accumulation and adipogenic gene expression. Collectively, the data herein support a role for the MPCs in adipogenesis in a 3-D environment and that they may contribute to the ectopic accumulation of adipose tissue. The observation that the potential for adipogenic differentiation is maintained even after a period of myogenic differentiation alludes to the possibility that adipogenesis may occur during different phases of muscle development. Finally, the increase in adipogenic differentiation in hydrogels containing MPCs derived from diabetic animals provides strong evidence that a pathological environment in vivo increases their capacity for adipogenesis.
异位脂肪组织在骨骼肌中的发展与多种骨骼肌和代谢疾病有关，包括 2 型糖尿病。肌肉前体细胞（MPC）的脂肪生成分化被认为是在体内以三维（3-D）构型发生在骨骼肌中；因此，使用体外 3-D 基质来研究这种现象是合适的。通过用在增加脂质积累和激活与脂肪生成分化相关的基因表达方面能力不同的脂肪生成诱导培养基处理源自健康或糖尿病动物的 MPC，研究了 MPC 在 3-D 环境中的脂肪生成分化能力。如果肌生成分化先于 MPC 暴露于脂肪生成诱导条件，则脂肪生成分化的能力降低，但不会被阻止。相反，与源自瘦大鼠的 MPC 相比，源自糖尿病大鼠的 MPC 在含有 MPC 的水凝胶中的脂肪生成分化更大，这表现为脂质积累和脂肪生成基因表达增加。总的来说，这些数据支持 MPC 在 3-D 环境中的脂肪生成中的作用，并且它们可能有助于异位脂肪组织的积累。观察到即使在肌生成分化一段时间后，脂肪生成分化的潜力仍然保持，这暗示了脂肪生成可能发生在肌肉发育的不同阶段。最后，糖尿病动物来源的 MPC 水凝胶中脂肪生成分化的增加提供了强有力的证据，表明体内病理环境增加了它们的脂肪生成能力。
