Decreased UCP-1 expression in beige adipocytes from adipose-derived stem cells of type 2 diabetes patients associates with mitochondrial ROS accumulation during obesity

Michurina, Svetlana; Stafeev, Iurii; Podkuychenko, Nikita; Sklyanik, Igor A.; Shestakova, Ekaterina A.; Yahyaev, Kamil; Yurasov, Anatoliy; Ratner, E. I.; Menshikov, Mikhail; Parfyonova, Yelena; Shestakova, Marina Vladimirovna

doi:10.1016/j.diabres.2020.108410

Cited by 10 publications

(6 citation statements)

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“…Moreover, diabetic conditions are characterized by the decreased angiogenesis and differentiation of ADSCs in both human and animal models [ 15 , 16 ]. T2DM, especially, significantly suppresses white and beige adipogenesis [ 11 , 17 , 18 , 19 ]. Based on the fact that ADSC osteogenesis and adipogenesis are in a reciprocal relationship due to the mutual repression of the RUNX2 (master regulator of osteogenesis) and PPARγ (master regulator of adipogenesis) transcription factors [ 20 , 21 , 22 ], we hypothesize that the suppression of adipogenesis can be the result of activated ADSC osteogenesis in T2DM.…”

Section: Introductionmentioning

confidence: 99%

Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity

Agareva

Stafeev

Michurina

et al. 2022

Life

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Objective: Sedentary behavior with overnutrition provokes the development of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The main progenitor cells of adipose tissue are adipose-derived stem cells (ADSCs) which can change differentiation, metabolic, and secretory phenotypes under obesity conditions. The purpose of this study was to evaluate ADSC osteogenesis activity among patients with obesity in normal glucose tolerance (NGT) and T2DM conditions. Methods: In the study, ADSCs from donors with obesity were used. After clinical characterization, all patients underwent bariatric surgery and ADSCs were isolated from subcutaneous fat biopsies. ADSCs were subjected to osteogenic differentiation, stained with Alizarin Red S, and harvested for real-time PCR and Western blotting. Cell senescence was evaluated with a β-galactosidase-activity-based assay. Results: Our results demonstrated the significantly increased calcification of ADSC on day 28 of osteogenesis in the T2DM group. These data were confirmed by the statistically significant enhancement of RUNX2 gene expression, which is a master regulator of osteogenesis. Protein expression analysis showed the increased expression of syndecan 1 and collagen I before and during osteogenesis, respectively. Moreover, T2DM ADSCs demonstrated an increased level of cellular senescence. Conclusion: We suggest that T2DM-associated cellular senescence can cause ADSC differentiation to shift toward osteogenesis, the impaired formation of new fat depots in adipose tissue, and the development of insulin resistance. The balance between ADSC adipo- and osteogenesis commitment is crucial for the determination of the metabolic fate of patients and their adipose tissue.

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Section: Introductionmentioning

confidence: 99%

Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity

Agareva

Stafeev

Michurina

et al. 2022

Life

Self Cite

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“…Patient-dependent individual factors, such as high age, adiposity, comorbidities, or possible treatments could have a negative effect on ADSC's regenerative potential to grow and differentiate and therefore on their secretome [10,[39][40][41][42]. There still is the need for further experiments with ADSCs from different patients to analyze their interindividual differences, their impact on ADSC behavior [43,44], and, in a next step, their influence on wound healing.…”

Section: Discussionmentioning

confidence: 99%

IGF-I and Hyaluronic Acid Mitigate the Negative Effect of Irradiation on Human Skin Keratinocytes

Sörgel

Schmid

Stadelmann

et al. 2022

Cancers

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Ionizing radiation has become an integral part of modern cancer therapy regimens. Various side effects, such as radiation dermatitis, affect patients in acute and chronic forms and decrease therapy compliance significantly. In this study, primary keratinocytes were irradiated in a 2-dimensional (2D) culture as well as on a 3-dimensional (3D) collagen-elastin matrix with doses of 2 and 5 Gy. The effect of different concentrations of IGF-I, KGF, platelet lysate (PL), high and low molecular weight hyaluronic acid (H-HA, L-HA), and adipose-derived stem cell (ADSC) conditioned medium was analyzed in respect to cell viability (WST-8), wound closure (migration), and the gene expression (quantitative real-time PCR) of 2D cultures. The 3D culture was evaluated by WST-8. A mixture of H-HA and L-HA, as well as IGF-I, could significantly stimulate the keratinocyte viability and migration which were severely reduced by irradiation. The MKI67and IL6 gene expression of irradiated keratinocytes was significantly higher after H-HA/L-HA treatment. The stimulating effects of H-HA/L-HA and IGF-I were able to be confirmed in 3D culture. A positive influence on cell viability, migration, and gene expression was achieved after the treatment with H-L-HA and IGF-I. These results open the possibility of a novel therapeutic method for both the prevention and the treatment of radiation dermatitis.

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“…A recent study observed a decreased UCP1 expression in beige adipocytes derived from adipose-derived stem cells of patients with T2DM. This reduction in UCP1 expression, along with the accumulation of ROS, may contribute to the thermogenic dysfunction of beige adipocytes 78 . Activation of UCP1 in skeletal muscle has shown beneficial effects, including reducing fasting blood glucose levels, lowering body weight, and reversing glucose intolerance in genetically engineered obese mice 79 .…”

Section: Solute Carrier Transporters In Glucose Metabolismmentioning

confidence: 99%

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Le,

Chen,

Yang

et al. 2024

Acta Pharmaceutica Sinica B

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Decreased UCP-1 expression in beige adipocytes from adipose-derived stem cells of type 2 diabetes patients associates with mitochondrial ROS accumulation during obesity

Cited by 10 publications

References 48 publications

Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity

Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity

IGF-I and Hyaluronic Acid Mitigate the Negative Effect of Irradiation on Human Skin Keratinocytes

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

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