Mitochondrial Respiration of Adipocytes Differentiating From Human Mesenchymal Stem Cells Derived From Adipose Tissue

Abstract

Burden of obesity is increasing in the contemporary world. Although multifactorial in origin, appropriate mitochondrial function of adipocytes emerges as a factor essential for healthy adipocyte differentiation and adipose tissue function. Our study aimed to evaluate mitochondrial functions of human adipose-derived mesenchymal stem cells committed to adipogenesis. On days 0, 4, 10, and 21 of adipogenesis, we have characterized adipocyte proliferation and viability, quantified lipid accumulation in maturing cells, performed qualitative and quantitative analysis of mitochondria, determined mitochondrial respiration of cells using high-resolution respirometry, and evaluated mitochondrial membrane potential. In the course of adipogenesis, mitochondrial oxygen consumption progressively increased in states ROUTINE and E (capacity of the electron transfer system). State LEAK remained constant during first days of adipogenesis and then increased probably reflecting uncoupling ability of maturing adipocytes. Citrate synthase activity and volume of mitochondrial networks increased during differentiation, particularly between days 10 and 21. In addition, lipid accumulation remained low until day 10 and then significantly increased. In conclusion, during first days of adipogenesis, increased mitochondrial respiration is needed for transition of differentiating cells from glycolytic to oxidative metabolism and clonal expansion of preadipocytes and then more energy is needed to acquire typical metabolic phenotype of mature adipocyte.

Chronic DDE Exposure Modifies Mitochondrial Respiration during Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Mature Adipocytes

“…The excess E-R capacity (respiratory reserve) was the only parameter compromised by the long-lasting exposure to DMSO (between days 10 and 21 of differentiation). Nevertheless, the same trend was observed in DDE-treated adipocytes on day 21 verifying our previous finding that in the later stages of differentiation, the routine respiration could be increased only on the account of the total electron-transporting capacity of mitochondria [3]. In addition, the ratio of routine to maximal respiration (R/E) was nearly the same in DMSO-control and DDE-treated adipocytes on day 21 of the experiment and in all these groups it reached significantly higher values than on day 10 of differentiation.…”

“…We compared JC1 staining in unaffected adipocyte differentiation and in differentiation under the influence of DMSO and DMSO with DDE. In all cases, we observed a gradual decrease in the red/green ratio during differentiation, which corresponds to previous findings [3,29]. On the fourth day of differentiation, a significant decrease in MMP was observed in DDE-affected cells at both 1 µM and 10 µM concentrations compared to medium containing DMSO alone.…”

“…We found that the long-lasting treatment with DDE in a concentration of 1 µM in contrast to 10 µM resulted in statistically significant deviations in mitochondrial respiration compared to control cells. The characteristic pattern of changes in mitochondrial respiration during adipogenesis was not impaired by lower DDE concentration showing a typical gradual increase in the routine and leak respirations of maturing adipocytes [3]. However, on day 21 of the experiment-i.e., in adipocytes regarded as fully differentiated-higher mitochondrial membrane potential, higher resting mitochondrial oxygen consumption (routine respiration), and higher ATP-related respiration (R-L) were observed in DDE 1 µM samples compared to relevant controls.…”

“…In the course of adipogenesis, mitochondrial oxygen consumption progressively increases. During the first days of adipogenesis, mitochondrial oxygen consumption is needed for the transition of differentiating cells from glycolytic to oxidative metabolism and the clonal expansion of preadipocytes, and then more energy is needed to acquire the typical metabolic phenotype of mature adipocyte [3].…”

Ischemic-hypoxic preconditioning enhances the mitochondrial function recovery of transplanted olfactory mucosa mesenchymal stem cells via miR-181a signaling in ischemic stroke

“…Mitochondria play an important role in the energy metabolism of the brain and the regulation of Ca2+ balance in cells. Mitochondria are also the primary contributor to the production of ROS [ 32 , 33 ]. The process of apoptosis triggered by neuronal injury in cerebral ischemia has been shown to involve mitochondrial dysfunction [ 34 , 35 ].…”