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

Agareva, Margarita; Stafeev, Iurii; Michurina, Svetlana; Sklyanik, Igor A.; Shestakova, Ekaterina A.; Ratner, E. I.; Xiang, Huimin; Menshikov, Mikhail; Shestakova, Marina Vladimirovna; Parfyonova, Yelena

doi:10.3390/life12050688

Cited by 5 publications

(2 citation statements)

References 61 publications

(71 reference statements)

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“…However, the ER stress marker and insulin resistance were not elevated in Class II + III obese subjects, albeit the more adiposity and higher BMI values. In line with these results, the decreased expression of adipogenic genes in obese subjects with type 2 diabetes compared to non-diabetic obese subjects has been reported [27].…”

Section: Discussionsupporting

confidence: 74%

Subcutaneous adipocyte size but not adiposity was associated with inflammation, ER stress, and insulin resistance markers

Pourdashti

Faridi

Monem-Homaie

et al. 2023

Preprint

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Background: The fat storage capability of the adipose tissue prevents ectopic lipid deposition, which is one of the risk factors for metabolic abnormalities in obesity. This capability depends on the adipogenic gene expression and blood supply provision for tissue expansion through angiogenesis. Here, we studied hyperplasia/hypertrophy of subcutaneous white adipose tissue (scWAT) concerning adipogenic gene expression, angiogenic status, and metabolic parameters in non-obese, Class I, and Class II+III obese subjects. Methods: The scWAT samples were collected from 80 subjects. The anthropometric parameters, adipose tissue cell size, serum biochemistry, ER stress induced XBP1 splicing, PPARγ2, SFRP1, WNT10B, and VEGFA gene expression levels were studied. In addition, the CD31 level was investigated by Western blotting. Results: The obese subjects had greater waist circumferences and higher serum TG, TC, insulin, and HOMA-IR than the non-obese group. The Class I obese group showed the largest adipocyte size, increased TNFα, insulin, HOMA-IR, and sXBP-1, WNT10B, and VEGFAexpression. In contrast, the expression of SFRP1 was not significantly different between all studied groups. The Class II+III obesity group showed high PPARγ2 expression and CD31 levels. Class I obesity, with hypertrophic scWAT adipocytes and limited capability of adipose tissue expansion, showed inflammation, insulin resistance, and ER stress. Conclusion: The results suggest that the capability of adipogenesis with inadequate angiogenesis is related to metabolic status, inflammation, and ER function. Therefore, therapeutic strategies to simultaneously promote angiogenesis and adipogenesis can effectively prevent obesity complications.

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Section: Discussionsupporting

confidence: 74%

Subcutaneous adipocyte size but not adiposity was associated with inflammation, ER stress, and insulin resistance markers

Pourdashti

Faridi

Monem-Homaie

et al. 2023

Preprint

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“…It is known that ADSCs are susceptible to hyperglycemia-induced oxidative stress-mediated senescence with activation of p53 and growth arrest [ 20 , 21 , 22 ]. Furthermore, increased levels of glyoxal (GO) and MGO, observed in diabetes and aging, can induce cellular senescence in ECs [ 11 ].…”

Section: Resultsmentioning

confidence: 99%

Methylglyoxal Impairs the Pro-Angiogenic Ability of Mouse Adipose-Derived Stem Cells (mADSCs) via a Senescence-Associated Mechanism

Leone

Nicolò

Prevenzano

et al. 2023

Cells

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Adipose-derived stem cells (ADSCs) play a crucial role in angiogenesis and repair of damaged tissues. However, in pathological conditions including diabetes, ADSC function is compromised. This work aims at evaluating the effect of Methylglyoxal (MGO), a product of chronic hyperglycemia, on mouse ADSCs’ (mADSCs) pro-angiogenic function and the molecular mediators involved. The mADSCs were isolated from C57bl6 mice. MGO-adducts and p-p38 MAPK protein levels were evaluated by Western Blot. Human retinal endothelial cell (hREC) migration was analyzed by transwell assays. Gene expression was measured by qRT-PCR, and SA-βGal activity by cytofluorimetry. Soluble factor release was evaluated by multiplex assay. MGO treatment does not impair mADSC viability and induces MGO-adduct accumulation. hREC migration is reduced in response to both MGO-treated mADSCs and conditioned media from MGO-treated mADSCs, compared to untreated cells. This is associated with an increase of SA-βGal activity, SASP factor release and p53 and p21 expression, together with a VEGF- and PDGF-reduced release from MGO-treated mADSCs and a reduced p38-MAPK activation in hRECs. The MGO-induced impairment of mADSC function is reverted by senolytics. In conclusion, MGO impairs mADSCs’ pro-angiogenic function through the induction of a senescent phenotype, associated with the reduced secretion of growth factors crucial for hREC migration.

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The size of human subcutaneous adipocytes, but not adiposity, is associated with inflammation, endoplasmic reticulum stress, and insulin resistance markers

et al. 2023

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Background The fat storage capacity of the adipose tissue prevents ectopic lipid deposition, which is one of the risk factors for metabolic abnormalities in obesity. This capacity depends upon the adipogenic gene expression and blood supply provision for tissue expansion through angiogenesis. Here, we studied hyperplasia/hypertrophy of subcutaneous white adipose tissue (scWAT) concerning adipogenic gene expression, angiogenic status, and metabolic parameters in non-obese and different classes of obese individuals. Methods The scWAT samples were collected from 80 individuals. The anthropometric parameters, adipose tissue cell size, serum biochemistry, ER stress-induced XBP1 splicing, PPARγ2, SFRP1, WNT10B, and VEGFA gene expression levels were studied. In addition, the CD31 level was investigated by Western blotting. Results The obese individuals had greater waist circumferences and higher serum TG, TC, insulin, and HOMA-IR than the non-obese group. However, the largest adipocyte size, increased TNFα, insulin, and HOMA-IR, and the highest expression level of sXBP1, WNT10B, and VEGFA were observed in Class I obese individuals. It means that inflammation, insulin resistance, and ER stress accompany hypertrophic scWAT adipocytes with limited adipose tissue expansion ability. Furthermore, the Class II + III obese individuals showed high PPARγ2 expression and CD31 levels. There is adipogenesis through hyperplasia in this group. The SFRP1 expression was not significantly different in the studied groups. Conclusion The results suggest that the capability of adipogenesis with inadequate angiogenesis is related to the metabolic status, inflammation, and ER function. Therefore, therapeutic strategies that support both angiogenesis and adipogenesis can effectively prevent the complications of obesity.

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

Cited by 5 publications

References 61 publications

Subcutaneous adipocyte size but not adiposity was associated with inflammation, ER stress, and insulin resistance markers

Subcutaneous adipocyte size but not adiposity was associated with inflammation, ER stress, and insulin resistance markers

Methylglyoxal Impairs the Pro-Angiogenic Ability of Mouse Adipose-Derived Stem Cells (mADSCs) via a Senescence-Associated Mechanism

The size of human subcutaneous adipocytes, but not adiposity, is associated with inflammation, endoplasmic reticulum stress, and insulin resistance markers

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