• 제목/요약/키워드: human adipose tissue

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Adipose tissue macrophage heterogeneity in the single-cell genomics era

  • Haneul Kang;Jongsoon Lee
    • Molecules and Cells
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    • 제47권2호
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    • pp.100031.1-100031.13
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    • 2024
  • It is now well-accepted that obesity-induced inflammation plays an important role in the development of insulin resistance and type 2 diabetes. A key source of the inflammation is the murine epididymal and human visceral adipose tissue. The current paradigm is that obesity activates multiple proinflammatory immune cell types in adipose tissue, including adipose-tissue macrophages (ATMs), T Helper 1 (Th1) T cells, and natural killer (NK) cells, while concomitantly suppressing anti-inflammatory immune cells such as T Helper 2 (Th2) T cells and regulatory T cells (Tregs). A key feature of the current paradigm is that obesity induces the anti-inflammatory M2 ATMs in lean adipose tissue to polarize into proinflammatory M1 ATMs. However, recent single-cell transcriptomics studies suggest that the story is much more complex. Here we describe the single-cell genomics technologies that have been developed recently and the emerging results from studies using these technologies. While further studies are needed, it is clear that ATMs are highly heterogeneous. Moreover, while a variety of ATM clusters with quite distinct features have been found to be expanded by obesity, none truly resemble classical M1 ATMs. It is likely that single-cell transcriptomics technology will further revolutionize the field, thereby promoting our understanding of ATMs, adipose-tissue inflammation, and insulin resistance and accelerating the development of therapies for type 2 diabetes.

혈관내피세포 채취의 원천으로 인간 지방조직의 활용 (Use of Human Adipose Tissue as a Source of Endothelial Cells)

  • 박봉욱;하영술;김진현;조희영;정명희;김덕룡;김욱규;김종렬;장중희;변준호
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제32권4호
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    • pp.299-305
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    • 2010
  • Purpose: Adipose tissue is located beneath the skin, around internal organs, and in the bone marrow in humans. Its main role is to store energy in the form of fat, although it also cushions and insulates the body. Adipose tissue also has the ability to dynamically expand and shrink throughout the life of an adult. Recently, it has been shown that adipose tissue contains a population of adult multipotent mesenchymal stem cells and endothelial progenitor cells that, in cell culture conditions, have extensive proliferative capacity and are able to differentiate into several lineages, including, osteogenic, chondrogenic, endothelial cells, and myogenic lineages. Materials and Methods: This study focused on endothelial cell culture from the adipose tissue. Adipose tissues were harvested from buccal fat pad during bilateral sagittal split ramus osteotomy for surgical correction of mandibular prognathism. The tissues were treated with 0.075% type I collagenase. The samples were neutralized with DMEM/and centrifuged for 10 min at 2,400 rpm. The pellet was treated with 3 volume of RBC lysis buffer and filtered through a 100 ${\mu}m$ nylon cell strainer. The filtered cells were centrifuged for 10 min at 2,400 rpm. The cells were further cultured in the endothelial cell culture medium (EGM-2, Cambrex, Walkersville, Md., USA) supplemented with 10% fetal bovine serum, human EGF, human VEGF, human insulin-like growth factor-1, human FGF-$\beta$, heparin, ascorbic acid and hydrocortisone at a density of $1{\times}10^5$ cells/well in a 24-well plate. Low positivity of endothelial cell markers, such as CD31 and CD146, was observed during early passage of cells. Results: Increase of CD146 positivity was observed in passage 5 to 7 adipose tissue-derived cells. However, CD44, representative mesenchymal stem cell marker, was also strongly expressed. CD146 sorted adipose tissue-derived cells was cultured using immuno-magnetic beads. Magnetic labeling with 100 ${\mu}l$ microbeads per 108 cells was performed for 30 minutes at $4^{\circ}C$ a using CD146 direct cell isolation kit. Magnetic separation was carried out and a separator under a biological hood. Aliquous of CD146+ sorted cells were evaluated for purity by flow cytometry. Sorted cells were 96.04% positivity for CD146. And then tube formation was examined. These CD146 sorted adipose tissue-derived cells formed tube-like structures on Matrigel. Conclusion: These results suggest that adipose tissue-derived cells are endothelial cells. With the fabrication of the vascularized scaffold construct, novel approaches could be developed to enhance the engineered scaffold by the addition of adipose tissue-derived endothelial cells and periosteal-derived osteoblastic cells to promote bone growth.

Vitamin D regulation of adipogenesis and adipose tissue functions

  • Nimitphong, Hataikarn;Park, Eunmi;Lee, Mi-Jeong
    • Nutrition Research and Practice
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    • 제14권6호
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    • pp.553-567
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    • 2020
  • Vitamin D insufficiency is associated with obesity and its related metabolic diseases. Adipose tissues store and metabolize vitamin D and expression levels of vitamin D metabolizing enzymes are known to be altered in obesity. Sequestration of vitamin D in large amount of adipose tissues and low vitamin D metabolism may contribute to the vitamin D inadequacy in obesity. Vitamin D receptor is expressed in adipose tissues and vitamin D regulates multiple aspects of adipose biology including adipogenesis as well as metabolic and endocrine function of adipose tissues that can contribute to the high risk of metabolic diseases in vitamin D insufficiency. We will review current understanding of vitamin D regulation of adipose biology focusing on vitamin D modulation of adiposity and adipose tissue functions as well as the molecular mechanisms through which vitamin D regulates adipose biology. The effects of supplementation or maintenance of vitamin D on obesity and metabolic diseases are also discussed.

Dysregulation of Cannabinoid CB1 Receptor Expression in Subcutaneous Adipocytes of Obese Individuals

  • Lee, Yong-Ho;Tharp, William G.;Dixon, Anne E.;Spaulding, Laurie;Trost, Susanne;Nair, Saraswathy;Permana, Paska A.;Pratley, Ridhard E.
    • Animal cells and systems
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    • 제13권4호
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    • pp.371-379
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    • 2009
  • The endocannabinoid system (ECS) plays a key role in the regulation of appetite, body weight and metabolism. We undertook the present study to further clarify the regulation of the cannabinoid CB1 receptor (CB1, CNR1) in human adipose tissue in obesity. CB1 receptor mRNA expression was ~1.6-fold (p<0.004) and 1.9-fold higher (P<0.05) in subcutaneous adipocytes from obese compared to non-obese subjects in microarray and quantitative real-time PCR studies, respectively. Higher CB1 receptor mRNA expression levels in both adipose tissue (~1.2 fold, P<0.05) and adipocytes (~2 fold, P<0.01) were observed in samples from visceral compared to subcutaneous depots collected from 22 obese individuals. Immunofluorescence confocal microscopy demonstrated the presence of CB1 receptor on adipocytes and also adipose tissue macrophages. These data indicate that adipocyte CB1 receptor is up-regulated in human obesity and visceral adipose tissue and also suggest a potential role for the ECS in modulating immune/inflammation as well as fat metabolism in adipose tissue.

A Physiologically Based Pharmacokinetic Model for Absorption and Distribution of Imatinib in Human Body

  • Chowdhury, Mohammad Mahfuz;Kim, Do-Hyun;Ahn, Jeong-Keun
    • Bulletin of the Korean Chemical Society
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    • 제32권11호
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    • pp.3967-3972
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    • 2011
  • A whole body physiologically based pharmacokinetic (PBPK) model was applied to investigate absorption, distribution, and physiologic variations on pharmacokinetics of imatinib in human body. Previously published pharmacokinetic data of the drug after intravenous (i.v.) infusion and oral administration were simulated by the PBPK model. Oral dose absorption kinetics were analyzed by adopting a compartmental absorption and transit model in gut section. Tissue/plasma partition coefficients of drug after i.v. infusion were also used for oral administration. Sensitivity analysis of the PBPK model was carried out by taking parameters that were commonly subject to variation in human. Drug concentration in adipose tissue was found to be higher than those in other tissues, suggesting that adipose tissue plays a role as a storage tissue for the drug. Variations of metabolism in liver, body weight, and blood/plasma partition coefficient were found to be important factors affecting the plasma concentration profile of drug in human body.

The Relationship of a Combination of Human Adipose Tissue-Derived Stem Cells and Frozen Fat with the Survival Rate of Transplanted Fat

  • Ha, Ki-Young;Park, Hojin;Park, Seung-Ha;Lee, Byung-Il;Ji, Yi-Hwa;Kim, Tae-Yeon;Yoon, Eul-Sik
    • Archives of Plastic Surgery
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    • 제42권6호
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    • pp.677-685
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    • 2015
  • Background The survival rate of grafted fat is difficult to predict, and repeated procedures are frequently required. In this study, the effects of the freezing period of harvested adipose tissue and the addition of human adipose tissue-derived stem cells (ASCs) on the process of fat absorption were studied. Methods Adipose tissue was obtained from patients who underwent a lipoaspirated fat graft. The fat tissue was cryopreserved at $-20^{\circ}C$ in a domestic refrigerator. A total of 40 nude mice were used. The mice in the experimental group received three different subcutaneous injections in the back: an injection of fresh fat and ASCs, an injection of fat that had been frozen for one month and ASCs, and an injection of fat that had been frozen for two months and ASCs. The control mice received fat grafts without ASCs. The mice were sacrificed at four or eight weeks after the procedure, and the grafted fat tissues were harvested. The extracted fat was evaluated using photographic analysis, volume measurements, and histological examination. Results In the control group, the fat resorption rates four weeks after transplantation in the grafts of fresh fat, fat that had been frozen for one month, and fat that had been frozen for two months were 21.14%, 22.46%, and 42.56%, respectively. In the experimental group, the corresponding resorption rates were 6.68%, 13.0%, and 33.9%, respectively. Conclusions ASCs can increase the fat graft survival rate. The use of ASCs in fat grafting can reduce the need for repeated fat grafts and provide good long term results.

지방줄기세포가 무세포 분쇄진피기질(Acellular micronized dermal matrix) 부착에 있어 Avidin과 Biotin의 효과 (Effect of Avidin and Biotin in Attachment of Human Adipose Stem Cells to Micronized Acellular Dermal Matrix)

  • 유결;이종원;임진수
    • Archives of Plastic Surgery
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    • 제35권1호
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    • pp.1-6
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    • 2008
  • Purpose: In tissue engineering, it is important that the scaffolds have high affinity with cells for making efficient use of cells. The authors studied the binding affinity of human adipose stem cells(ASCs) to micronized acellular dermal matrix(alloderm) using biotin and avidin linkages.Methods: Human ASCs were harvested from adipose tissue obtained by abdominoplasty. ASCs($1{\times}10^4$, $5{\times}10^4$, $1{\times}10^5$, $5{\times}10^5$, $1{\times}10^6$, $5{\times}10^6$ cells) were attached to micronized alloderm(1mg) in three groups; 1) control group in which no ASCs and alloderm was treated; 2) serum group in which alloderm was exposed to fetal bovine serum; and 3) biotin group in which biotinylated cells were attached to biotinylated alloderm. The binding affinities were determined 1 day after making ASC-alloderm complexes. The proliferation rates were determined by XTT assays in 4, 7, 14, and 21 days and scanning electron microscopic examination was performed in 7 and 21 days after culture of ASC-alloderm complexes.Results: The binding affinities of the biotin group were significantly increased in all cell concentrations. Maximum binding affinity was observed at $5{\times}10^4/mg$ of micronized dermal matrix in biotin group. The viabilities were lowest in biotin group in contrast to binding affinity, but the difference was not significant. SEM showed well attachment of cells to micronized dermal matrix in all groups. Conclusion: The use of avidin/biotin facilitated human ASCs attaching to micronized acellular dermal matrix. This attachment would not disturb adipose stem cells viabilities. The present study suggests that avidin/ biotin can be used as making efficient use of cells in adipose tissue engineering.

$17{\beta}$-estradiol Represses White Adipose Tissue Metabolism by Inhibiting $PPAR{\gamma}$ in High Fat Diet-induced Obese Female Ovariectomized Mice

  • Yoon, Mi-Chung;Jeong, Sun-Hyo
    • 대한의생명과학회지
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    • 제15권3호
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    • pp.171-177
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    • 2009
  • This study investigated whether increased adiposity is prevented by estrogen replacement in female ovariectomized (OVX) C57BL/6J mice, an animal model of human menopause and whether these metabolic changes reflect the inhibitory action of estrogen on peroxisome proliferator-activated receptor $\gamma$ ($PPAR{\gamma}$)-regulated gene expression. Treatment of $17{\beta}$-estradiol for the last one week of the experiment decreased high fat diet-induced body weight gain and white adipose tissue mass compared to OVX control mice. Histological analysis showed that administration of $17{\beta}$-estradiol to mice decreased the size of adipocytes in parametrial adipose tissue versus OVX control mice. In addition, $17{\beta}$-estradiol reduced the adipose expression of $PPAR{\gamma}$ as well as $PPAR{\gamma}$ target genes such as adipocyte fatty acid binding protein and tumor necrosis factor $\alpha$. These results suggest that $17{\beta}$-estradiol may inhibit adiposity through reducing the $PPAR{\gamma}$ activities in female OVX mice.

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비만에서의 혈관신생의 역할 (The Role of Angiogenesis in Obesity)

  • 윤미정
    • 생명과학회지
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    • 제24권5호
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    • pp.573-587
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    • 2014
  • 혈관신생은 모든 조직의 성장과 발달, 그리고 상처회복 등에 매우 중요하다. 지방조직은 우리 몸에서 가장 혈관이 발달된 조직으로서 각 지방세포들은 모세혈관에 둘러싸여 있으며 신생혈관들은 지방세포에 영양분과 산소를 공급한다. 혈관의 내피세포들은 파라크린 신호경로, 세포외 성분, 세포들 간의 직접적인 작용을 통해 지방세포와 교류한다. 활성화된 지방세포들은 VEGF, FGF-2, leptin, HGF와 같은 혈관신생인자들을 생성하며, 이들은 단독으로 혹은 협력하여 혈관신생을 증가시키고 지방조직의 성장과 대사를 촉진한다. 따라서 혈관신생 억제제들은 비만과 비만관련 질환을 치료하는데 유용할 것으로 생각된다.