Low proliferative potential of adipose-derived stromal cells associates with hypertrophy and inflammation in subcutaneous and omental adipose tissue of patients with type 2 diabetes mellitus

Stafeev, Iurii; Podkuychenko, Nikita; Michurina, Svetlana; Sklyanik, Igor A.; Panevina, A S; Shestakova, Ekaterina A.; Yahyaev, Kamil; Fedenko, V. S.; Ratner, E. I.; Vorotnikov, Alexander V.; Menshikov, Mikhail; Yashkov, Yu I; Parfyonova, Y.; Shestakova, Marina Vladimirovna

doi:10.1016/j.jdiacomp.2018.10.011

Cited by 18 publications

(12 citation statements)

References 60 publications

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“…Therefore, ADSCs are currently recognized as promising therapeutic candidates for tissue repair and regeneration ( 7 , 8 ). The proliferation and adipogenesis of ADSCs are essential for the maintenance of metabolic homeostasis particularly in adipose tissue, as supported by our previous study showing distinct metabolic influences on WAT homeostasis by ADSCs from different anatomic locations ( 41 , 42 ). Notably, human or mouse ADSCs showed strong capacity for immunomodulation through actively participating in both innate and adaptive immunity, such as promoting macrophage polarization toward anti-inflammatory phenotypes or inducing regulatory T cell differentiation.…”

Section: Cells In Adipose Tissue Related To Immunometabolismsupporting

confidence: 61%

Adipose Extracellular Vesicles: Messengers From and to Macrophages in Regulating Immunometabolic Homeostasis or Disorders

et al. 2021

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Adipose tissue is comprised of heterogenous cell populations that regulate both energy metabolism and immune reactions. Macrophages play critical roles in regulating immunometabolic homeostasis or disorders through cooperation with adipocytes, adipose tissue-derived stem cells (ADSCs) or other cells in adipose tissue. Extracellular vesicles (EVs) are recently recognized as efficient messengers for intercellular communication. Emerging evidences have demonstrated that adipose EVs are actively involved in the mutual interactions of macrophages, adipocytes and ADSCs, which produce considerable influences on immunometabolism under healthy or obese conditions. Here, we will elaborate the production and the characteristics of adipose EVs that are related to macrophages under different metabolic demands or stresses, whilst discuss the roles of these EVs in regulating local or systemic immunometabolic homeostasis or disorders in the context of adipocyte-macrophage dialogue and ADSC-macrophage interaction. Particularly, we provide a profile of dynamic adipose microenvironments based on macrophages. Adipose EVs act as the messengers between ADSCs and macrophages to maintain the balance of metabolism and immunity, while drive a vicious cycle between hypertrophic adipocytes and inflammatory macrophages to cause immunometabolic imbalance. This review may provide valuable information about the physio- or pathological roles of adipose EVs and the application of adipose EVs in the diagnosis and treatment of metabolic diseases.

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Section: Cells In Adipose Tissue Related To Immunometabolismsupporting

confidence: 61%

Adipose Extracellular Vesicles: Messengers From and to Macrophages in Regulating Immunometabolic Homeostasis or Disorders

et al. 2021

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“…Another possible explanation for the discrepancy is that rodent studies often used epididymal/intra-abdominal rather than subcutaneous adipose tissue for measurements; there is no analogous human depot to epididymal fat. Other reports indicate either no difference in (41,42) or less inflammation (3) and macrophage burden (22) in visceral than in subcutaneous fat. In support of our findings, 18 mo after bariatric surgery, patients were reported to have no significant changes in subcutaneous ATM in the face of improved insulin sensitivity (20).…”

Section: Discussionmentioning

confidence: 95%

Adipose tissue macrophage burden, systemic inflammation, and insulin resistance

Jia

Morgan‐Bathke

Jensen

2020

American Journal of Physiology-Endocrinology and Metabolism

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Adipose tissue inflammation, as defined by macrophage accumulation, is proposed to cause insulin resistance and systemic inflammation. Because the strength of this relationship for humans is unclear, we tested whether adipose tissue macrophage (ATM) burden is correlated with these health indicators. Using immunohistochemistry, we measured abdominal subcutaneous CD68+ (total ATM), CD14+ (proinflammatory/M1), and CD206+ (anti-inflammatory/M2) ATM in 97 volunteers (BMI 20–38 kg/m2, in addition to body composition, adipocyte size, homeostasis model assessment of insulin resistance, ADIPO-IR, adipose tissue insulin resistance measured by palmitate, plasma lipids, TNF, and IL-6 concentrations. There were several significant univariate correlations between metabolic parameters to IL-6 and ATM per 100 adipocytes, but not ATM per gram tissue; adipocyte size was a confounding variable. We used matching strategies and multivariate regression analyses to investigate the relationships between ATM and inflammatory/metabolic parameters independent of adipocyte size. Matching approaches revealed that the groups discordant for CD206 but concordant for adipocyte size had significantly different fasting insulin and IL-6 concentrations. However, groups discordant for adipocyte size but concordent for ATM differeded in that visceral fat, plasma triglyceride, glucose, and TNF concentrations were greater in those with large adipocytes. Multivariate regression analysis indicated that indexes of insulin resistance and fasting triglycerides were predicted by body composition; the predictive value of ATM per 100 adipocytes or per gram tissue was variable between males and females. We conclude that the relationship between ATM burden and metabolic/inflammatory variables is confounded by adipocyte size/body composition and that ATM do not predict insulin resistance, systemic inflammation, or dyslipidemia. ATM may primarily play a role in tissue remodeling rather than in metabolic pathology.

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“…In turn, RUNX2 is a transcription master regulator of osteogenic differentiation of mesenchymal precursors, and SMAD4 is a shuttle-protein for conducting SMADs in heterodimers to RUNX2 (34, 35). SMAD4-RUNX2 signal cascade is a critical participant not only in osteogenic differentiation but also in the regulation of chondrocyte hypertrophy (36). Reciprocal antagonistic relations between adipogenesis and osteogenesis are now well-described.…”

Section: Discussionmentioning

confidence: 99%

Role of MicroRNAs in the Regulation of Subcutaneous White Adipose Tissue in Individuals With Obesity and Without Type 2 Diabetes

et al. 2019

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Obesity is a high-risk factor for such comorbidities as cardiovascular disease, several types of cancer, and type 2 diabetes; however not all individuals with obesity have such complications. Approximately 20% of individuals with obesity are metabolically healthy. This study focused on differences between obese individuals with and without type 2 diabetes (T2D+ and T2D–, respectively) on the transcriptome level. Subjects included were 35 T2D– patients with obesity and 35 T2D+ patients with obesity with the same body mass index (BMI). The study was based on the transcription analysis of mRNA and microRNAs (miRs) by RNAseq. In the first step, we performed RNAseq of miRs, in the second step, we analyzed only those mRNA, which appeared targets for significant miRs from the first step. All RNAseq results were validated by qPCR. There were seven miRs differently expressed with adjusted p-value <0.1, which were confirmed by qPCR. Five among them: miR-204-5p, miR125b-5p, miR-125a-5p, miR320a, miR-99b—were upregulated in T2D+ patients with obesity, while only two miRs, miR-23b-3p, and miR197-3p, were increased in T2D– patients with obesity. These seven miRs target two groups of genes: matrix metalloproteinases and TGFβ signal pathway genes. According to the results of transcriptome analysis, the main difference between T2D+ and T2D– patients with obesity was in adipogenesis and fibrosis regulation by matrix metalloproteinases and SMAD4-RUNX2 signal cascade. Based on the data about transcription profiles of both groups, we suggested that the process of fibrosis in T2D+ patients with obesity is more pronounced than in T2D– patients with obesity.

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Low proliferative potential of adipose-derived stromal cells associates with hypertrophy and inflammation in subcutaneous and omental adipose tissue of patients with type 2 diabetes mellitus

Cited by 18 publications

References 60 publications

Adipose Extracellular Vesicles: Messengers From and to Macrophages in Regulating Immunometabolic Homeostasis or Disorders

Adipose Extracellular Vesicles: Messengers From and to Macrophages in Regulating Immunometabolic Homeostasis or Disorders

Adipose tissue macrophage burden, systemic inflammation, and insulin resistance

Role of MicroRNAs in the Regulation of Subcutaneous White Adipose Tissue in Individuals With Obesity and Without Type 2 Diabetes

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