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 ◽  
...  

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.

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Sun ◽  
Xinchu Ni ◽  
Suping Sun ◽  
Leiming Cai ◽  
Jingping Yu ◽  
...  

We aim to investigate the effects of adipose-derived stem cells (ASCs) transplantation on irradiation-induced skeletal muscle fibrosis. Sixty-four rabbits were randomly divided into ASCs group and PBS group followed by irradiation at unilateral hip with a single dose of 80 Gy. Nonirradiated side with normal skeletal muscle served as normal control. Skeletal muscle tissues were collected from eight rabbits in each group at 1 w, 4 w, 8 w, and 26 w after irradiation. Migration of ASCs was observed in the peripheral tissues along the needle passage in the injured muscle. The proportion of the area of collagen fibers to the total area in sections of ASCs group was lower than those of PBS groups at 4 w, 8 w, and 26 w after irradiation. Significant decrease was noted in the integrated optimal density of the transforming growth factorβ1 (TGF-β1) in the ASCs group compared with those of PBS group at 4 w, 8 w, and 26 w after irradiation. Moreover, the expression of TGF-β1 was lower in the ASCs group compared to those of the PBS group at each time point determined by Western blot analysis. ASCs transplantation could alleviate irradiation fibrosis by suppressing the level of TGF-β1 in the irradiated skeletal muscle.


2018 ◽  
Vol 234 (2) ◽  
pp. 1452-1460 ◽  
Author(s):  
Hisashi Kato ◽  
Hidemasa Minamizato ◽  
Hideki Ohno ◽  
Yoshinobu Ohira ◽  
Tetsuya Izawa

2021 ◽  
Author(s):  
Katarina Andjelkov ◽  
Ilya Eremin ◽  
Aleksandra Korac

Abstract BACKGROUND Hair follicles and underlying adipose tissue show highly coordinated interaction through exchange of different signaling molecules. We conducted a study to investigate the quantitative and qualitative secretome profiling of Adipose Derived Stem Cells (ADSCs) from different zones of hair growth in patients with Androgenetic Alopecia (AGA).METHODSWe included 6 male patients, candidates for follicular unit extraction hair transplantation, all in early stage of AGA. 1mm punch samples of adipose tissue located beneath hair follicles of 3 scalp areas (alopecia, border-line and normal hair growth) and 1 periumbilical sample were analyzed.Samples were enzymatically digested, centrifuged, washed, and cell pellets were ceded and maintained in culture medium until reached monolayer. Conditioned media samples were thawed and analyzed with 41plex kit. Results were registered by Magpix device (Luminex platform) and calculated with xPonent software. We analyzed the levels of 35 signaling proteins.RESULTSThe level of Inteleukin-6 (IL-6) were significantly higher in the alopecia zone in comparison to the periumbilical and occipital, alongside with the levels of Vascular Endothelial Growth Factor (VEGF), Endothelial Growth Factor (EGF) and Eotaxin. The similar trend was found for Monocyte Chemotactic Protein-3 (MCP-3), Interferon gamma-inducible Protein-10 (IP-10) and Macrophage Inflammatory Protein - 1 alpha (MIP-1𝛼), while, on the other side, Monocyte Chemoattractant Protein-1 (MCP-1) level was the lowest in alopecia comparing to other zones. All other examined proteins did not shown changes in their expression level.CONCLUSIONHence, knowledge of differences in these signaling molecules expression will be essential for both, achieving therapeutic goals for hair loss conditions and shading more lights on the AGA etiology.


2021 ◽  
Vol 22 (2) ◽  
pp. 966
Author(s):  
Seita Osawa ◽  
Hisashi Kato ◽  
Yuki Maeda ◽  
Hisashi Takakura ◽  
Junetsu Ogasawara ◽  
...  

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.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 287-LB
Author(s):  
HYE-JIN LEE ◽  
MUN-GYU SONG ◽  
NA-HEE HA ◽  
BO-YEONG JIN ◽  
SANG-HYUN CHOI ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2501
Author(s):  
Maihemuti Mijiti ◽  
Ryosuke Mori ◽  
Bingyu Huang ◽  
Kenichiro Tsukamoto ◽  
Keisuke Kiriyama ◽  
...  

Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 days. Serum cholesterol levels were significantly lower in the protamine and RPR groups than in the control group. White adipose tissue weight was significantly decreased in the protamine and RPR groups. The fecal excretion of cholesterol and bile acid was significantly higher in the protamine and RPR groups than in the control group. We also observed a significant decrease in the expression of hepatic SCD1, SREBP1, and adipocyte FAS mRNA, and significantly increased expression of hepatic PPARα and adipocyte PPARγ1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPARγ1 and hepatic PPARα and the downregulation of hepatic SCD1 via SREBP1 and adipocyte FAS. RPR derived from protamine has a crucial role in the anti-obesity action of protamine by evaluating the effective dose of adipose tissue weight loss.


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