Exercise ameliorates high-fat diet-induced impairment of differentiation of adipose-derived stem cells into neuron-like cells in rats

2018 ◽  
Vol 234 (2) ◽  
pp. 1452-1460 ◽  
Author(s):  
Hisashi Kato ◽  
Hidemasa Minamizato ◽  
Hideki Ohno ◽  
Yoshinobu Ohira ◽  
Tetsuya Izawa
Keyword(s):  
Stem Cells ◽  
High Fat Diet ◽  
Adipose Derived Stem Cells ◽  
High Fat

scholarly journals Metabolomic Profiles in Adipocytes Differentiated from Adipose-Derived Stem Cells Following Exercise Training or High-Fat Diet

2021 ◽  
Vol 22 (2) ◽  
pp. 966
Author(s):  
Seita Osawa ◽  
Hisashi Kato ◽  
Yuki Maeda ◽  
Hisashi Takakura ◽  
Junetsu Ogasawara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amino Acid ◽  
Exercise Training ◽  
High Fat Diet ◽  
Principal Component ◽  
Normal Diet ◽  
Adipose Derived Stem Cells ◽  
High Fat ◽  
Metabolome Analysis ◽  
Differentiation Potential

Controlling the differentiation potential of adipose-derived stem cells (ADSCs) is attracting attention as a new strategy for the prevention and treatment of obesity. Here, we aimed to observe the effect of exercise training (TR) and high-fat diet (HFD) on the metabolic profiles of ADSCs-derived adipocytes. The rats were divided into four groups: normal diet (ND)-fed control (ND-SED), ND-fed TR (ND-TR), HFD-fed control (HFD-SED), and HFD-fed TR (HFD-TR). After 9 weeks of intervention, ADSCs of epididymal and inguinal adipose tissues were differentiated into adipocytes. In the metabolome analysis of adipocytes after isoproterenol stimulation, 116 metabolites were detected. The principal component analysis demonstrated that ADSCs-derived adipocytes segregated into four clusters in each fat pad. Amino acid accumulation was greater in epididymal ADSCs-derived adipocytes of ND-TR and HFD-TR, but lower in inguinal ADSCs-derived adipocytes of ND-TR, than in the respective controls. HFD accumulated several metabolites including amino acids in inguinal ADSCs-derived adipocytes and more other metabolites in epididymal ones. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that TR mainly affected the pathways related to amino acid metabolism, except in inguinal ADSCs-derived adipocytes of HFD-TR rats. These findings provide a new way to understand the mechanisms underlying possible changes in the differentiation of ADSCs due to TR or HFD.

scholarly journals A High-Fat Diet Promotes Mammary Gland Myofibroblast Differentiation through MicroRNA 140 Downregulation

2016 ◽  
Vol 37 (4) ◽  
Author(s):  
Benjamin Wolfson ◽  
Yongshu Zhang ◽  
Ramkishore Gernapudi ◽  
Nadire Duru ◽  
Yuan Yao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Myofibroblast Differentiation ◽  
Adipose Derived Stem Cells ◽  
High Fat ◽  
Breast Adipose Tissue ◽  
Tgf Β1

ABSTRACT Human breast adipose tissue is a heterogeneous cell population consisting of mature white adipocytes, multipotent mesenchymal stem cells, committed progenitor cells, fibroblasts, endothelial cells, and immune cells. Dependent on external stimulation, adipose-derived stem cells differentiate along diverse lineages into adipocytes, chondrocytes, osteoblasts, fibroblasts, and myofibroblasts. It is currently not fully understood how a high-fat diet reprograms adipose-derived stem cells into myofibroblasts. In our study, we used mouse models of a regular diet and of high-fat-diet-induced obesity to investigate the role of dietary fat on myofibroblast differentiation in the mammary stromal microenvironment. We found that a high-fat diet promotes myofibroblast differentiation by decreasing microRNA 140 (miR-140) expression in mammary adipose tissue through a novel negative-feedback loop. Increased transforming growth factor β1 (TGF-β1) in mammary adipose tissue in obese mice activates SMAD3 signaling, causing phospho-SMAD3 to bind to the miR-140 locus and inhibit miR-140 transcription. This prevents miR-140 from targeting SMAD3 for degradation, resulting in amplified TGF-β1/SMAD3 signaling and miR-140 downregulation-dependent myofibroblast differentiation. Using tissue and coculture models, we found that myofibroblasts and the fibrotic microenvironment created by myofibroblasts impact the stemness and proliferation of normal ductal epithelial cells and early-stage breast cancer invasion and stemness.

scholarly journals Identification of Sox2 and NeuN Double-Positive Cells in the Mouse Hypothalamic Arcuate Nucleus and Their Reduction in Number With Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Ayumu Sugiura ◽  
Tatsuhiro Shimizu ◽  
Takeshi Kameyama ◽  
Tomohiko Maruo ◽  
Shin Kedashiro ◽  
...  
Keyword(s):  
Stem Cells ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
High Fat ◽  
Double Positive ◽  
Diet Induced Obesity ◽  
Hypothalamic Arcuate Nucleus ◽  
Hypothalamic Cells ◽  
Induced Changes ◽  
Insight Into

The hypothalamus plays a central role in homeostasis and aging. The hypothalamic arcuate nucleus (ARC) controls homeostasis of food intake and energy expenditure and retains adult neural stem cells (NSCs)/progenitor cells. Aging induces the loss of NSCs and the enhancement of inflammation, including the activation of glial cells in the ARC, but aging-associated alterations of the hypothalamic cells remain obscure. Here, we identified Sox2 and NeuN double-positive cells in a subpopulation of cells in the mouse ARC. These cells were reduced in number with aging, although NeuN-positive neuronal cells were unaltered in the total number. Diet-induced obesity mice fed with high-fat diet presented a similar hypothalamic alteration to aged mice. This study provides a new insight into aging-induced changes in the hypothalamus.

scholarly journals Epigenomic Regulation of SATB2 Links Maternal Obesity to Impaired Osteoblast Differentiation (P11-034-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jin-Ran Chen ◽  
Haijun Zhao ◽  
Oxana P Lazarenko ◽  
Kartik Shankar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Epigenetic Regulation ◽  
High Fat Diet ◽  
Osteoblast Differentiation ◽  
Maternal Obesity ◽  
Control Diet ◽  
High Fat ◽  
Pregnant Mothers

Abstract Objectives Nutritional status during intrauterine and/or early postnatal life has substantial influences on adult offspring health. However, evidence on the impact of high fat diet (HFD)-induced maternal obesity on regulation of fetal bone development is sparse. Thus, we investigated the effects of maternal obesity in rodent and human cells on epigenetic regulation of osteoblast differentiation. Methods First, female Sprague-Dawley rats were fed either a low-fat AIN-93G control diet or a high fat diet (HFD) (45% fat calories) for 10 wk starting at 6 wk of age. Lean (from control diet) and obese (from HFD) female rats were then time-impregnated (n = 6 per group) by control diet fed male rats. At gestational day 18.5 (E18.5), all fetuses were taken and embryonic osteogenic calvarial cells (EOCCs) were isolated. Second, human osteo-progenitors of mesenchymal stem cells were isolated from umbilical cord following delivery from pregnant mothers. Results We found epigenetic regulation of polycomb-regulated gene Ezh2 (Enhancer of zeste homolog 2) in embryonic rats from HFD obese rat dams. Increased enrichment of repressive histone mark H3K27me3 on the gene body of SATB2 (ChIP Seq analysis) was associated with aberrant differentiation of EOCCs to mature osteoblasts. Knocking down Ezh2 in EOCCs and ST2 cells increased SATB2 expression; on the other hand, Ezh2 overexpression in EOCCs and ST2 cells decreased SATB2 expression. These data were consistent with ChIP experimental results showing strong association between H3K27me3, Ezh2 and SATB2. Second, human mesenchymal stem cells (MSCs) from umbilical cord (UC) were isolated following delivery from obese/overweight (pre-pregnancy BMI ≥ 25 kg/m2) and control (pre-pregnancy BMI between 19–25 kg/m2) pregnant mothers. We found: 1) UC-MSCs from pregnant obese/overweight mothers showed increased Ezh2 expression and decreased SATB2 mRNA expression, which was concurrent lower osteoblastogenesis potential in EOCCs; 2) ChIP experiments using H3K27me3 IP (immune-precipitation) showed significant association between H3K27me3, Ezh2 and SATB2. Conclusions These findings indicate maternal HFD-induced obesity-associated decrease of fetal pre-osteoblastic cell differentiation is under epigenetic control through SATB2 expression. Funding Sources Supported by USDA-ARS Project.

scholarly journals Differences in Hematopoietic Stem Cells Contribute to Sexually Dimorphic Inflammatory Responses to High Fat Diet-induced Obesity

2015 ◽  
Vol 290 (21) ◽  
pp. 13250-13262 ◽  
Author(s):  
Kanakadurga Singer ◽  
Nidhi Maley ◽  
Taleen Mergian ◽  
Jennifer DelProposto ◽  
Kae Won Cho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Sexually Dimorphic ◽  
High Fat ◽  
Hematopoietic Stem ◽  
Diet Induced Obesity

scholarly journals Interleukin-6 Knockout Inhibits Senescence of Bone Mesenchymal Stem Cells in High-Fat Diet-Induced Bone Loss

2021 ◽  
Vol 11 ◽  
Author(s):  
Yujue Li ◽  
Lingyun Lu ◽  
Ying Xie ◽  
Xiang Chen ◽  
Li Tian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
Interleukin 6 ◽  
High Fat Diet ◽  
Cell Senescence ◽  
Low Grade ◽  
High Fat ◽  
Bone Mesenchymal Stem Cells

Obesity, a chronic low-grade inflammatory state, not only promotes bone loss, but also accelerates cell senescence. However, little is known about the mechanisms that link obesity, bone loss, and cell senescence. Interleukin-6 (IL-6), a pivotal inflammatory mediator increased during obesity, is a candidate for promoting cell senescence and an important part of senescence-associated secretory phenotype (SASP). Here, wild type (WT) and (IL-6 KO) mice were fed with high-fat diet (HFD) for 12 weeks. The results showed IL-6 KO mice gain less weight on HFD than WT mice. HFD induced trabecular bone loss, enhanced expansion of bone marrow adipose tissue (BMAT), increased adipogenesis in bone marrow (BM), and reduced the bone formation in WT mice, but it failed to do so in IL-6 KO mice. Furthermore, IL-6 KO inhibited HFD-induced clone formation of bone marrow cells (BMCs), and expression of senescence markers (p53 and p21). IL-6 antibody inhibited the activation of STAT3 and the senescence of bone mesenchymal stem cells (BMSCs) from WT mice in vitro, while rescued IL-6 induced senescence of BMSCs from IL-6 KO mice through the STAT3/p53/p21 pathway. In summary, our data demonstrated that IL-6 KO may maintain the balance between osteogenesis and adipogenesis in BM, and restrain senescence of BMSCs in HFD-induced bone loss.

scholarly journals CXCL2 Impairs Functions of Bone Marrow Mesenchymal Stem Cells and Can Serve as a Serum Marker in High-Fat Diet-Fed Rats

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianhai Bi ◽  
Qiuchen Li ◽  
Zhigang Yang ◽  
Lei Cai ◽  
Tao Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Serum Marker ◽  
Cytokine Signaling ◽  
Low Grade ◽  
High Fat

In modern society excessive consumption of a high-fat diet (HFD) is a significant risk factor for many diseases such as diabetes, osteoarthritis and certain cancers. Resolving cellular and molecular mechanisms underlying HFD-associated disorders is of great importance to human health. Mesenchymal stem cells (MSCs) are key players in tissue homeostasis and adversely affected by prolonged HFD feeding. Low-grade systemic inflammation induced by HFD is characterized by increased levels of pro-inflammatory cytokines and alters homeostasis in many organs. However, whether, which and how HFD associated inflammatory cytokines impair MSCs remain unclear. Here we demonstrated that HFD induced serum cytokines disturbances, especially a continuous elevation of serum CXCL2 level in rats. Coincidentally, the differentially expressed genes (DEGs) of bone marrow MSCs (BMSCs) which functions were impaired in HFD rats were enriched in cytokine signaling. Further mechanism analysis revealed that CXCL2 treatment in vitro suppresses the adipogenic potential of BMSCs via Rac1 activation, and promoted BMSC migration and senescence by inducing over-production of ELMO1 and reactive oxygen species (ROS) respectively. Moreover, we found that although glycolipid metabolism indicators can be corrected, the CXCL2 elevation and BMSC dysfunctions cannot be fully rescued by diet correction and anti-inflammatory aspirin treatment, indicating the long-lasting deleterious effects of HFD on serum CXCL2 levels and BMSC functions. Altogether, our findings identify CXCL2 as an important regulator in BMSCs functions and may serve as a serum marker to indicate the BMSC dysfunctions induced by HFD. In addition, our findings underscore the intricate link among high-fat intake, chronic inflammation and BMSC dysfunction which may facilitate development of protective strategies for HFD associated diseases.

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