Interleukin 21 Receptor Affects Adipogenesis of Human Adipose-Derived Stem/Stromal Cells

Dysfunctions in adipose tissue cells are responsible for several obesity-related metabolic diseases. Understanding the process of adipocyte formation is thus fundamental for understanding these diseases. The adipocyte differentiation of adipose-derived stem/stromal cells (ADSCs) showed a reduction in the mRNA level of the interleukin 21 receptor (IL21R) during this process. Although the receptor has been associated with metabolic diseases, few studies have examined its function in stem cells. In this study, we used confocal immunofluorescence assays to determine that IL21R colocalizes with mitochondrial protein ATP5B, ALDH4A1, and the nucleus of human ADSCs. We demonstrated that silencing and overexpression of IL21R did not affect the cell proliferation and mitochondrial activity of ADSCs. However, IL21R silencing did reduce ADSC adipogenic capacity. Further studies are needed to understand the mechanism involved between IL21R and the adipogenic differentiation process.

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Effects of Extreme High Temperatures on Proliferation, Cell Cycle, Cell Differentiation and ROS of Adipose-Derived Mesenchymal Stromal Cells

10.21203/rs.3.rs-764300/v1 ◽

2021 ◽

Author(s):

Yuanhui Gao ◽

Hui Cao ◽

Shunlan Wang ◽

Linlin Zheng ◽

Haowei He ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

High Temperature ◽

Cell Differentiation ◽

Osteogenic Differentiation ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Adipogenic Differentiation ◽

Mitochondrial Activity ◽

Growth Activity

Abstract Backgrounds: Global warming has led to extreme temperatures in different latitudinal regions, resulting in the extinction of a large number of species. This study focuses on the effects of extreme high temperatures on cell proliferation, cell cycle, cell differentiation and mitochondria activity in human adipose-derived mesenchymal stromal cells (hADSCs). Methods: hADSCs were divided into three groups and incubated in 37°C, 39°C and 40°C environment for 5 hours of exposure each day, and then to 37°C circumstances for further incubation. Cell surface markers, cell cycle, cell proliferation activity, mitochondrial activity and cell polarization were detected and analyzed by flow cytometry, CCK-8 assay, ROS and JC-1 staining respectively on the 1 st and 3 rd day of cell culture; osteogenic and adipogenic differentiation ability of hASCs was analyzed by staining after 21 days of osteogenic and adipogenic differentiation induction culture. Results The results of this study showed that hASCs grown under high temperature conditions had restricted growth activity, blocked S and G2 phases of the cell cycle, reduced cytokinesis and impaired mitochondrial activity, while their osteogenic differentiation ability and membrane potential depolarization were enhanced. Conclusions: hADSCs were subjected to high temperature stimulation with restricted growth activity, reduced cell division, impaired mitochondrial activity, significant cell depolarization and enhanced osteogenic differentiation, and these results were closely related to the pathogenic mechanisms of skin aging and heat stroke due to outdoor sun exposure.

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Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽

10.3390/cells10020268 ◽

2021 ◽

Vol 10 (2) ◽

pp. 268

Author(s):

Jonathan Ribot ◽

Cyprien Denoeud ◽

Guilhem Frescaline ◽

Rebecca Landon ◽

Hervé Petite ◽

...

Keyword(s):

Type 2 Diabetes ◽

Bone Marrow ◽

Stromal Cells ◽

Adipogenic Differentiation ◽

Therapeutic Modality ◽

Multipotent Stromal Cells ◽

Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

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Bone marrow stromal cells from MDS and AML patients show increased adipogenic potential with reduced Delta-like-1 expression

Scientific Reports ◽

10.1038/s41598-021-85122-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Marie-Theresa Weickert ◽

Judith S. Hecker ◽

Michèle C. Buck ◽

Christina Schreck ◽

Jennifer Rivière ◽

...

Keyword(s):

Bone Marrow ◽

Cell Fate ◽

Stromal Cells ◽

Adipogenic Differentiation ◽

Cell Types ◽

Bone Marrow Niche ◽

Differentiation Potential ◽

Hematopoietic Stem ◽

Bm Niche

AbstractMyelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell disorders with a poor prognosis, especially for elderly patients. Increasing evidence suggests that alterations in the non-hematopoietic microenvironment (bone marrow niche) can contribute to or initiate malignant transformation and promote disease progression. One of the key components of the bone marrow (BM) niche are BM stromal cells (BMSC) that give rise to osteoblasts and adipocytes. It has been shown that the balance between these two cell types plays an important role in the regulation of hematopoiesis. However, data on the number of BMSC and the regulation of their differentiation balance in the context of hematopoietic malignancies is scarce. We established a stringent flow cytometric protocol for the prospective isolation of a CD73+ CD105+ CD271+ BMSC subpopulation from uncultivated cryopreserved BM of MDS and AML patients as well as age-matched healthy donors. BMSC from MDS and AML patients showed a strongly reduced frequency of CFU-F (colony forming unit-fibroblast). Moreover, we found an altered phenotype and reduced replating efficiency upon passaging of BMSC from MDS and AML samples. Expression analysis of genes involved in adipo- and osteogenic differentiation as well as Wnt- and Notch-signalling pathways showed significantly reduced levels of DLK1, an early adipogenic cell fate inhibitor in MDS and AML BMSC. Matching this observation, functional analysis showed significantly increased in vitro adipogenic differentiation potential in BMSC from MDS and AML patients. Overall, our data show BMSC with a reduced CFU-F capacity, and an altered molecular and functional profile from MDS and AML patients in culture, indicating an increased adipogenic lineage potential that is likely to provide a disease-promoting microenvironment.

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Effect of fluoxetine treatment on mitochondrial bioenergetics in central and peripheral rat tissues

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2014-0462 ◽

2015 ◽

Vol 40 (6) ◽

pp. 565-574 ◽

Cited By ~ 15

Author(s):

Aline Isabel da Silva ◽

Glauber Ruda Feitoza Braz ◽

Reginaldo Silva-Filho ◽

Anderson Apolonio Pedroza ◽

Diorginis Soares Ferreira ◽

...

Keyword(s):

Skeletal Muscle ◽

Metabolic Diseases ◽

Mitochondrial Permeability Transition ◽

Permeability Transition ◽

Wistar Rat ◽

Male Rats ◽

Mitochondrial Activity ◽

Rat Tissues ◽

Transferase Activity ◽

Mitochondrial Bioenergetics

Recent investigations have focused on the mitochondrion as a direct drug target in the treatment of metabolic diseases (obesity, metabolic syndrome). Relatively few studies, however, have explicitly investigated whether drug therapies aimed at changing behavior by altering central nervous system (CNS) function affect mitochondrial bioenergetics, and none has explored their effect during early neonatal development. The present study was designed to evaluate the effects of chronic treatment of newborn male rats with the selective serotonin reuptake inhibitor fluoxetine on the mitochondrial bioenergetics of the hypothalamus and skeletal muscle during the critical nursing period of development. Male Wistar rat pups received either fluoxetine (Fx group) or vehicle solution (Ct group) from the day of birth until 21 days of age. At 60 days of age, mitochondrial bioenergetics were evaluated. The Fx group showed increased oxygen consumption in several different respiratory states and reduced production of reactive oxygen species, but there was no change in mitochondrial permeability transition pore opening or oxidative stress in either the hypothalamus or skeletal muscle. We observed an increase in glutathione S-transferase activity only in the hypothalamus of the Fx group. Taken together, our results suggest that chronic exposure to fluoxetine during the nursing phase of early rat development results in a positive modulation of mitochondrial respiration in the hypothalamus and skeletal muscle that persists into adulthood. Such long-lasting alterations in mitochondrial activity in the CNS, especially in areas regulating appetite, may contribute to permanent changes in energy balance in treated animals.

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Asiatic Acid Inhibits Adipogenic Differentiation of Bone Marrow Stromal Cells

Cell Biochemistry and Biophysics ◽

10.1007/s12013-013-9725-2 ◽

2013 ◽

Vol 68 (2) ◽

pp. 437-442 ◽

Cited By ~ 8

Author(s):

Zheng-Wei Li ◽

Cheng-dong Piao ◽

Hong-Hui Sun ◽

Xian-Sheng Ren ◽

Yun-Shen Bai

Keyword(s):

Bone Marrow ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Adipogenic Differentiation ◽

Marrow Stromal Cells ◽

Asiatic Acid

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N-acetyl-L-cysteine enhances the osteogenic differentiation and inhibits the adipogenic differentiation through up regulation of Wnt 5a and down regulation of PPARG in bone marrow stromal cells

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2011.04.020 ◽

2011 ◽

Vol 65 (5) ◽

pp. 369-374 ◽

Cited By ~ 17

Author(s):

HuiJiao Ji ◽

YuKan Liu ◽

XiaoLi Zhao ◽

Ming Zhang

Keyword(s):

Bone Marrow ◽

Osteogenic Differentiation ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Adipogenic Differentiation ◽

Marrow Stromal Cells ◽

Down Regulation

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Time course transcriptomic analysis of adipogenic differentiation of human white adipose tissue (WAT)-derived stromal cells

NURSA Datasets ◽

10.1621/d5ongvelpz ◽

2017 ◽

Author(s):

MA Ambele ◽

C Dessels ◽

C Durandt ◽

MS Pepper

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Stromal Cells ◽

Time Course ◽

Adipogenic Differentiation ◽

Transcriptomic Analysis

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Downregulation of DJ-1 Fails to Protect Mitochondrial Complex I Subunit NDUFS3 in the Testes and Contributes to the Asthenozoospermia

Mediators of Inflammation ◽

10.1155/2018/6136075 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Yupeng Wang ◽

Yi Sun ◽

Xin Zhao ◽

Renpei Yuan ◽

Hui Jiang ◽

...

Keyword(s):

Male Infertility ◽

Complex I ◽

Mitochondrial Protein ◽

Protein Product ◽

Mitochondrial Activity ◽

Mitochondrial Complex ◽

Specific Mechanism ◽

Nicotinamide Adenine Dinucleotide Dehydrogenase ◽

Complex I Activity ◽

Mitochondria Complex I

Asthenozoospermia (AS), an important cause of male infertility, is characterized by reduced sperm motility. Among the aetiologies of AS, inflammation seems to be the main cause. DJ-1, a conserved protein product of thePARK7gene, is associated with male infertility and plays a role in oxidative stress and inflammation. Although our previous studies showed that a reduction in DJ-1 was accompanied by mitochondrial dysfunction in the sperm of patients with AS, the specific mechanism underlying this association remained unclear. In this study, we found that compared to the patients without AS, the expression of mitochondrial protein nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3) was also significantly decreased in the sperm of patients with AS. Similarly, decreased expression of DJ-1 and NDUFS3 and reduced mitochondria complex I activity were evident in a rat model of AS. Moreover, we showed that the interaction between DJ-1 and NDUFS3 in rat testes was weakened by ORN treatment. These results suggest that the impaired mitochondrial activity could be due to the broken interaction between DJ-1 and NDUFS3 and that downregulation of DJ-1 in sperm and testes contributes to AS pathogenesis.

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MicroRNA-15a Regulates the Differentiation of Intramuscular Preadipocytes by Targeting ACAA1, ACOX1 and SCP2 in Chickens

International Journal of Molecular Sciences ◽

10.3390/ijms20164063 ◽

2019 ◽

Vol 20 (16) ◽

pp. 4063

Author(s):

Guoxi Li ◽

Shouyi Fu ◽

Yi Chen ◽

Wenjiao Jin ◽

Bin Zhai ◽

...

Keyword(s):

Target Gene ◽

Adipogenic Differentiation ◽

Mrna Level ◽

Chicken Breast ◽

Acid Oxidation ◽

Expression Levels ◽

Over Expression ◽

Triglyceride Accumulation ◽

Acyl Coa Oxidase ◽

Sterol Carrier Protein 2

Our previous studies showed that microRNA-15a (miR-15a) was closely related to intramuscular fat (IMF) deposition in chickens; however, its regulatory mechanism remains unclear. Here, we evaluated the expression characteristics of miR-15a and its relationship with the expression of acetyl-CoA acyltransferase 1 (ACAA1), acyl-CoA oxidase 1 (ACOX1) and sterol carrier protein 2 (SCP2) by qPCR analysis in Gushi chicken breast muscle at 6, 14, 22, and 30 weeks old, where we performed transfection tests of miR-15a mimics in intramuscular preadipocytes and verified the target gene of miR-15a in chicken fibroblasts (DF1). The miR-15a expression level at 30 weeks increased 13.5, 4.5, and 2.7-fold compared with the expression levels at 6, 14, and 22 weeks, respectively. After 6 days of induction, miR-15a over-expression significantly promoted intramuscular adipogenic differentiation and increased cholesterol and triglyceride accumulation in adipocytes. Meanwhile, 48 h after transfection with miR-15a mimics, the expression levels of ACAA1, ACOX1 and SCP2 genes decreased by 56.52%, 31.18% and 37.14% at the mRNA level in intramuscular preadipocytes. In addition, the co-transfection of miR-15a mimics and ACAA1, ACOX1 and SCP2 3′UTR (untranslated region) dual-luciferase vector significantly inhibited dual-luciferase activity in DF1 cells. Taken together, our data demonstrate that miR-15a can reduce fatty acid oxidation by targeting ACAA1, ACOX1, and SCP2, which subsequently indirectly promotes the differentiation of chicken intramuscular preadipocytes.

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