State Institute of Genetic and Regenerative Medicine NAMS of Ukraine, 67 Vyshgorodska Str., Kyiv, 04114, Ukraine.
Biotechnology Laboratory ilaya.regeneration, Medical Company ilaya, 9 I. Kramskogo Str., Kyiv, 03115, Ukraine.
Sci Rep. 2020 Mar 23;10(1):5217. doi: 10.1038/s41598-020-61983-3.
In this study, we performed an adipogenic differentiation of human adipose-derived stem cells (ADSCs) in vitro with different deuterium content (natural, low and high) in the culture medium during differentiation process with parallel analysis of the gene expression, metabolic activity and cell viability/toxicity. After ADSCs differentiation into adipocytes we have done the analysis of differentiation process efficiency and determined a type of resulting adipocytes (by morphology, gene expression, UCP1 protein detection and adipokine production analysis). We have found that high (5 × 10 ppm) deuterium content significantly inhibit in vitro adipogenic differentiation of human ADSCs compared to the groups with natural (150 ppm) and low (30 ppm) deuterium content. Importantly, protocol of differentiation used in our study leads to white adipocytes development in groups with natural (control) and high deuterium content, whereas deuterium-depleted differentiation medium leads to brown-like (beige) adipocytes formation. We have also remarked the direct impact of deuterium on the cellular survival and metabolic activity. Interesting, in deuterium depleted-medium, the cells had normal survival rate and high metabolic activity, whereas the inhibitory effect of deuterated medium on ADSCs differentiation at least was partly associated with deuterium cytotoxicity and inhibitory effect on metabolic activity. The inhibitory effect of deuterium on metabolic activity and the subsequent decrease in the effectiveness of adipogenic differentiation is probably associated with mitochondrial dysfunction. Thus, deuterium could be considered as an element that affects the substance chirality. These findings may be the basis for the development of new approaches in the treatment of obesity, metabolic syndrome and diabetes through the regulation of adipose-derived stem cell differentiation and adipocyte functions.
在这项研究中，我们在体外培养过程中使用不同氘含量（天然、低和高）的培养基对人脂肪来源干细胞（ADSCs）进行成脂分化，并进行平行分析基因表达、代谢活性和细胞活力/毒性。在 ADSCs 分化为脂肪细胞后，我们分析了分化过程的效率，并确定了产生的脂肪细胞的类型（通过形态、基因表达、UCP1 蛋白检测和脂肪因子产生分析）。我们发现，与天然（150ppm）和低（30ppm）氘含量组相比，高（5×10ppm）氘含量显著抑制人 ADSCs 的体外成脂分化。重要的是，我们研究中使用的分化方案导致天然（对照）和高氘含量组中白色脂肪细胞的发育，而氘耗尽的分化培养基导致棕色样（米色）脂肪细胞的形成。我们还注意到氘对细胞存活和代谢活性的直接影响。有趣的是，在氘耗尽的培养基中，细胞具有正常的存活率和高代谢活性，而氘化培养基对 ADSCs 分化的抑制作用至少部分与氘的细胞毒性和对代谢活性的抑制作用有关。氘对代谢活性的抑制作用以及随后成脂分化效果的降低可能与线粒体功能障碍有关。因此，氘可以被认为是影响物质手性的元素之一。这些发现可能为通过调节脂肪来源干细胞分化和脂肪细胞功能来治疗肥胖、代谢综合征和糖尿病提供新方法的发展提供依据。
