Name: Beyaz ve Kahverengi Yağ Greftleri: Siyah ve Ten Rengi Brachyury (BTBR) Obez Farelerde Üreme, Metabolik ve Böbrek Eksikliklerini Düzeltmeye Yönelik Bir Yaklaşım (Video) | JoVE Journal
Uploaded: 2025-09-09T13:45:00.000+00:00
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Description: Keşfedin, BTBR obez farelerde beyaz ve kahverengi yağ grefti kombinasyonunun üreme, metabolik ve böbrek fonksiyonlarını nasıl iyileştirdiğini. Bu standart protokol, obezite ve ilişkili komplikasyonlara karşı umut vadeden bir tedavi stratejisi sunar.

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<ol><li>Zhao, M., Cao, Y., Ma, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((New+insights+in+the+treatment+of+DKD%3A+recent+advances+and+future+prospects%5BTitle%5D)+AND+%22BMC+Nephrol%22%5BJournal%5D)">New insights in the treatment of DKD: recent advances and future prospects.</a> BMC Nephrol. 26 (1), 72(2025).</li>
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<li>Xu, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Trends+and+future+predictions+of+chronic+kidney+disease+due+to+diabetes+mellitus+type+2+attributable+to+dietary+risks%3A+insights+based+on+GBD+2021+data%5BTitle%5D)+AND+%22Front+Nutr%22%5BJournal%5D)">Trends and future predictions of chronic kidney disease due to diabetes mellitus type 2 attributable to dietary risks: insights based on GBD 2021 data.</a> Front Nutr. 11, 1494383(2024).</li>
<li>GBD 2021 Adult BMI Collaborators. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Adult+BMI+Collaborators.+Global%2C+regional%2C+and+national+prevalence+of+adult+overweight+and+obesity%2C+1990-2021%2C+with+forecasts+to+2050%3A+a+forecasting+study+for+the+Global+Burden+of+Disease+Study+2021%5BTitle%5D)+AND+%22Lancet%22%5BJournal%5D)">Adult BMI Collaborators. Global, regional, and national prevalence of adult overweight and obesity, 1990-2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021.</a> Lancet. 405 (10481), 813-838 (2025).</li>
<li>Liu, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Brown+adipose+tissue+transplantation+reverses+obesity+in+Ob%2FOb+mice%5BTitle%5D)+AND+%22Endocrinology%22%5BJournal%5D)">Brown adipose tissue transplantation reverses obesity in Ob/Ob mice.</a> Endocrinology. 156 (7), 2461-2469 (2015).</li>
<li>Ghesmati, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((An+update+on+the+secretory+functions+of+brown%2C+white%2C+and+beige+adipose+tissue%3A+Towards+therapeutic+applications%5BTitle%5D)+AND+%22Rev+Endocr+Metab+Disord%22%5BJournal%5D)">An update on the secretory functions of brown, white, and beige adipose tissue: Towards therapeutic applications.</a> Rev Endocr Metab Disord. 25 (2), 279-308 (2024).</li>
<li>Dewal, R. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Transplantation+of+committed+pre-adipocytes+from+brown+adipose+tissue+improves+whole-body+glucose+homeostasis%5BTitle%5D)+AND+%22iScience%22%5BJournal%5D)">Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis.</a> iScience. 27 (2), 108927(2024).</li>
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<li>Childs, G. V., Odle, A. K., MacNicol, M. C., MacNicol, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+importance+of+leptin+to+reproduction%5BTitle%5D)+AND+%22Endocrinology%22%5BJournal%5D)">The importance of leptin to reproduction.</a> Endocrinology. 162 (2), 1-18 (2021).</li>
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<li>Stanford, K. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Brown+adipose+tissue+regulates+glucose+homeostasis+and+insulin+sensitivity%5BTitle%5D)+AND+%22J+Clin+Invest%22%5BJournal%5D)">Brown adipose tissue regulates glucose homeostasis and insulin sensitivity.</a> J Clin Invest. 123 (1), 215-223 (2013).</li>
<li>Pinckard, K. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+novel+endocrine+role+for+the+BAT-released+Lipokine+12%2C13-diHOME+to+mediate+cardiac+function%5BTitle%5D)+AND+%22Circulation%22%5BJournal%5D)">A novel endocrine role for the BAT-released Lipokine 12,13-diHOME to mediate cardiac function.</a> Circulation. 143 (2), 145-159 (2021).</li>
<li>Valgas da Silva, P. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Brown+adipose+tissue+prevents+glucose+intolerance+and+cardiac+remodeling+in+high-fat-fed+mice+after+a+mild+myocardial+infarction%5BTitle%5D)+AND+%22Int+J+Obes+%28Lond%29%22%5BJournal%5D)">Brown adipose tissue prevents glucose intolerance and cardiac remodeling in high-fat-fed mice after a mild myocardial infarction.</a> Int J Obes (Lond). 46 (2), 350-358 (2022).</li>
<li>Zhang, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Brown+adipose+tissue+transplantation+ameliorates+diabetic+nephropathy+through+the+miR-30b+pathway+by+targeting+Runx1%5BTitle%5D)+AND+%22Metabolism%22%5BJournal%5D)">Brown adipose tissue transplantation ameliorates diabetic nephropathy through the miR-30b pathway by targeting Runx1.</a> Metabolism. 125, 154916(2021).</li>
<li>Clee, S. M., Nadler, S. T., Attie, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Genetic+and+genomic+studies+of+the+BTBR+ob%2Fob+mouse+model+of+type+2+diabetes%5BTitle%5D)+AND+%22Am+J+Ther%22%5BJournal%5D)">Genetic and genomic studies of the BTBR ob/ob mouse model of type 2 diabetes.</a> Am J Ther. 12 (6), 491-498 (2005).</li>
<li>Stoehr, J. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Identification+of+major+quantitative+trait+loci+controlling+body+weight+variation+in+ob%2Fob+mice%5BTitle%5D)+AND+%22Diabetes%22%5BJournal%5D)">Identification of major quantitative trait loci controlling body weight variation in ob/ob mice.</a> Diabetes. 53 (1), 245-249 (2004).</li>
<li>Liu, X., Zhang, Z., Song, Y., Xie, H., Dong, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((An+update+on+brown+adipose+tissue+and+obesity+intervention%3A+Function%2C+regulation+and+therapeutic+implications%5BTitle%5D)+AND+%22Front+Endocrinol+%28Lausanne%29%22%5BJournal%5D)">An update on brown adipose tissue and obesity intervention: Function, regulation and therapeutic implications.</a> Front Endocrinol (Lausanne). 13, 1065263(2022).</li>
<li>Mollah, M. L., Yang, H. S., Jeon, S., Kim, K., Cheon, Y. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Overaccumulation+of+fat+caused+rapid+reproductive+senescence+but+not+loss+of+ovarian+reserve+in+ob%2Fob+mice%5BTitle%5D)+AND+%22J+Endocr+Soc%22%5BJournal%5D)">Overaccumulation of fat caused rapid reproductive senescence but not loss of ovarian reserve in ob/ob mice.</a> J Endocr Soc. 5 (1), bvaa168(2021).</li>
<li>Serke, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Leptin-deficient+%28ob%2Fob%29+mouse+ovaries+show+fatty+degeneration%2C+enhanced+apoptosis+and+decreased+expression+of+steroidogenic+acute+regulatory+enzyme%5BTitle%5D)+AND+%22Int+J+Obes+%28Lond%29%22%5BJournal%5D)">Leptin-deficient (ob/ob) mouse ovaries show fatty degeneration, enhanced apoptosis and decreased expression of steroidogenic acute regulatory enzyme.</a> Int J Obes (Lond). 36 (8), 1047-1053 (2012).</li>
<li>Diamanti-Kandarakis, E., Dunaif, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Insulin+resistance+and+the+polycystic+ovary+syndrome+revisited%3A+an+update+on+mechanisms+and+implications%5BTitle%5D)+AND+%22Endocr+Rev%22%5BJournal%5D)">Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications.</a> Endocr Rev. 33 (6), 981-1030 (2012).</li>
<li>Chang, A. S., Dale, A. N., Moley, K. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Maternal+diabetes+adversely+affects+preovulatory+oocyte+maturation%2C+development%2C+and+granulosa+cell+apoptosis%5BTitle%5D)+AND+%22Endocrinology%22%5BJournal%5D)">Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis.</a> Endocrinology. 146 (5), 2445-2453 (2005).</li>
<li>Almog, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Leptin+attenuates+follicular+apoptosis+and+accelerates+the+onset+of+puberty+in+immature+rats%5BTitle%5D)+AND+%22Mol+Cell+Endocrinol%22%5BJournal%5D)">Leptin attenuates follicular apoptosis and accelerates the onset of puberty in immature rats.</a> Mol Cell Endocrinol. 183 (1-2), 179-191 (2001).</li>
<li>Beyerstedt, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Combining+sodium-glucose+co-transporter-2+inhibitor+with+mesenchymal+stem+cells+and+brown+adipose+tissue+%28BAT%29+and+white+adipose+tissue+%28WAT%29+transplantation+to+mitigate+the+progression+of+diabetic+kidney+disease%3A+a+pre-clinical+approach%5BTitle%5D)+AND+%22Stem+Cell+Res+Ther%22%5BJournal%5D)">Combining sodium-glucose co-transporter-2 inhibitor with mesenchymal stem cells and brown adipose tissue (BAT) and white adipose tissue (WAT) transplantation to mitigate the progression of diabetic kidney disease: a pre-clinical approach.</a> Stem Cell Res Ther. 16 (254), 1-15 (2025).</li>
<li>Sávio-Silva, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Therapeutic+potential+of+mesenchymal+stem+cells+in+a+pre-clinical+model+of+diabetic+kidney+disease+and+obesity%5BTitle%5D)+AND+%22Int+J+Mol+Sci%22%5BJournal%5D)">Therapeutic potential of mesenchymal stem cells in a pre-clinical model of diabetic kidney disease and obesity.</a> Int J Mol Sci. 22 (4), 1546(2021).</li>
<li>Takemura, S., Shimizu, T., Oka, M., Sekiya, S., Babazono, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Transplantation+of+adipose-derived+mesenchymal+stem+cell+sheets+directly+into+the+kidney+suppresses+the+progression+of+renal+injury+in+a+diabetic+nephropathy+rat+model%5BTitle%5D)+AND+%22J+Diabetes+Investig%22%5BJournal%5D)">Transplantation of adipose-derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model.</a> J Diabetes Investig. 11 (3), 545-553 (2020).</li>
<li>Pichaiwong, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Reversibility+of+structural+and+functional+damage+in+a+model+of+advanced+diabetic+nephropathy%5BTitle%5D)+AND+%22J+Am+Soc+Nephrol%22%5BJournal%5D)">Reversibility of structural and functional damage in a model of advanced diabetic nephropathy.</a> J Am Soc Nephrol. 24 (7), 1088-1102 (2013).</li>
<li>Almog, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Leptin+attenuates+follicular+apoptosis+and+accelerates+the+onset+of+puberty+in+immature+rats%5BTitle%5D)+AND+%22Mol+Cell+Endocrinol%22%5BJournal%5D)">Leptin attenuates follicular apoptosis and accelerates the onset of puberty in immature rats.</a> Mol Cell Endocrinol. 183 (1-2), 179-191 (2001).</li>
<li>O'Brien, P. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((BTBR+ob%2Fob+mice+as+a+novel+diabetic+neuropathy+model%3A+Neurological+characterization+and+gene+expression+analysis%5BTitle%5D)+AND+%22Neurobiol+Dis%22%5BJournal%5D)">BTBR ob/ob mice as a novel diabetic neuropathy model: Neurological characterization and gene expression analysis.</a> Neurobiol Dis. 73, 348-355 (2015).</li>
<li>Sávio-Silva, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Mesenchymal+stem+cell+therapy+for+diabetic+kidney+disease%3A+A+review+of+the+studies+using+syngeneic%2C+autologous%2C+allogenic%2C+and+xenogenic+cells%5BTitle%5D)+AND+%22Stem+Cells+Int%22%5BJournal%5D)">Mesenchymal stem cell therapy for diabetic kidney disease: A review of the studies using syngeneic, autologous, allogenic, and xenogenic cells.</a> Stem Cells Int. 2020, 8833725(2020).</li>
<li>Morsy, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Leptin+gene+therapy+and+daily+protein+administration%3A+a+comparative+study+in+the+ob%2Fob+mouse%5BTitle%5D)+AND+%22Gene+Ther%22%5BJournal%5D)">Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse.</a> Gene Ther. 5 (1), 8-18 (1998).</li>
<li>Wang, Y., Asakawa, A., Inui, A., Kosai, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Leptin+gene+therapy+in+the+fight+against+diabetes%5BTitle%5D)+AND+%22Expert+Opin+Biol+Ther%22%5BJournal%5D)">Leptin gene therapy in the fight against diabetes.</a> Expert Opin Biol Ther. 10 (10), 1405-1414 (2010).</li>
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</ol>

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beyaz ve kahverengi yağ greftleri: siyah ve ten rengi brachyury (btbr) obez farelerde Üreme, metabolik ve böbrek eksikliklerini düzeltmeye yönelik bir yaklaşım

White and Brown Adipose Grafts: An Approach to Correct Reproductive, Metabolic, and Renal Deficits in Black and Tan Brachyury (BTBR) Obese Mice

Beyaz ve Kahverengi Yağ Greftleri: Siyah ve Ten Rengi Brachyury (BTBR) Obez Farelerde Üreme, Metabolik ve Böbrek Eksikliklerini Düzeltmeye Yönelik Bir Yaklaşım

Transplantation of white adipose tissue (WAT) and brown adipose tissue (BAT) has emerged as a promising therapeutic strategy for reversing metabolic ...

white-brown-adipose-grafts-an-approach-to-correct-reproductive

Research

JoVE Journal

Biology

Biyoloji

Bu videoda, yeni doğmuş bir fareden deri altı beyaz yağ dokusunu ve interskapular kahverengi yağ dokusunu izole etmek için uygulanan cerrahi prosedürü gösteriyoruz.

Fare Yavrusundan Beyaz ve Kahverengi Yağ Deposu Toplama: Fare Yavrusundan Beyaz Yağ Dokusu ve Kahverengi Yağ Dokusunun Toplanması İçin Cerrahi Bir İşlem

Farelerde beyaz adipoz dokulardan izole İlköğretim beyaz preadipositlerden bej / brite hücrelerine ayırt edilebilir. Burada sunulan beyaz yağ "esmerleşme" moleküler düzenlenmesi okumak için güvenilir hücresel modeli sistemidir.

Bej / Brite Hücreler Stromal Vasküler Hücre İzolasyonu ve Farklılaşma

Bu makalede, alıcı hayvanların interscapular beyaz yağ yastığı içine donör sıçan meme epitel hücreleri greft bir transplantasyon yöntemi açıklanmaktadır. Bu yöntem, meme epitel gelişimi üzerindeki konak ve/veya donör etkilerini incelemek ve ön temizleme ihtiyacını ortadan kaldırmak ve böylece bu tekniğin kullanışlılığını genişletmek için kullanılabilir.

Interscapular Beyaz Yağ Ped içine Rat Mammary Epitel Hücre Nakli

Bu rapor, birincil kahverengi ve beyaz preadipositlerin yenidoğan farelerden eşzamanlı izolasyonu için bir protokol açıklanmaktadır. İzole hücreler kültürde yetiştirilebilir ve tamamen olgun beyaz ve kahverengi adipozitlere farklılaşmaya teşvik edilebilir. Yöntem, kültürdeki primer yağ hücrelerinin genetik, moleküler ve fonksiyonel olarak karakterizeini sağlar.

Primer Beyaz ve Kahverengi Preadipositlerin Yenidoğan Farelerden İzolasyonu ve Farklılaşması

Mikro-PET/MR görüntüleme tabanlı bir yaklaşım kullanılarak farelerde termojenik yağ depolarının fonksiyonel görüntülenmesi ve kantitasyonu.

[18F]FDG Micro-PET/MR Görüntüleme Kullanılarak Farelerde Kahverengi ve Bej Yağ Dokularının Görselleştirilmesi ve Ölçülmesi

Preadipositler, yenidoğan farelerden alınan interskapular kahverengi yağ dokusunun stromal vasküler fraksiyonundan izole edilir ve lipid damlacıkları biriktiren, moleküler belirteçleri eksprese eden ve olgun kahverengi adipositlerin mitokondriyal morfolojisini gösteren hücrelere farklılaşır. Bu hücreler ayrıca immünofloresan ve transmisyon elektron mikroskobu ile analiz edilir.

Yenidoğan Farelerden İnterskapular Yağ Dokusunun Stromal Vasküler Fraksiyonundan Kahverengi Adipositlerin Farklılaşması ve Görüntülenmesi

Burada, kemirgen veya insan yağ dokusundan izole edilen mikrovasküler fragmanların işlevsel, vaskülarize bej yağ dokusunun mühendisliğine basit bir yaklaşım olarak kullanımını özetleyen ayrıntılı bir protokol sunuyoruz.

Mikrovasküler Fragmanlardan Vaskülarize Termojenik Yağ Dokusunun Üç Boyutlu Kültürü

Bu protokol, bej yağ biyolojisini araştırmak için adeno ilişkili virüse (AAV) alternatif bir strateji olarak adipositlerde (AdipoSPH) CRISPR SunTag-p65-HSF1 (SPH) kullanımını sunmaktadır. Endojen Prdm16 genini hedef alan AAV taşıyan sgRNA'nın in vivo enjeksiyonu, bej yağ gelişimini indüklemek ve termojenik gen programını geliştirmek için yeterlidir.

CRISPR SunTag-p65-HSF1 Aktivasyon Sistemi Kullanılarak Bej Yağ Biyolojisi ve Metabolizmasının İncelenmesi

Bu protokolde, kombine bir Cre-LoxP, CRISPR-Cas9 ve adeno ilişkili virüs (AAV) tek kılavuzlu RNA (sgRNA) sisteminden yararlanarak kahverengi yağ dokusuna (BAT) özgü nakavt fareleri üretmek için teknik prosedürleri açıklıyoruz. Açıklanan adımlar, sgRNA'ların tasarımını, AAV-sgRNA parçacıklarının hazırlanmasını ve AAV'nin BAT loblarına mikroenjeksiyonunu içerir.

Kombine Cre-LoxP, CRISPR-Cas9 ve Adeno İlişkili Virüs Tek Kılavuzlu RNA Sistemi Kullanılarak Kahverengi Yağa Özgü Nakavt Farelerin Üretimi

Genetik Đndüklenebilir Kader Haritalama (GIFM) işaretleri ve ince, mekansal ve zamansal kontrolü ile parça...

Genetik Đndüklenebilir Kader Haritalama Pratik Bir Yaklaşım: Hücreler Mark ve Track Görsel Bir Rehberi In Vivo</em

Keşfedin, BTBR obez farelerde beyaz ve kahverengi yağ grefti kombinasyonunun üreme, metabolik ve böbrek fonksiyonlarını nasıl iyileştirdiğini. Bu standart protokol, obezite ve ilişkili komplikasyonlara karşı umut vadeden bir tedavi stratejisi sunar.

Beyaz ve Kahverengi Yağ Greftleri: Siyah ve Ten Rengi Brachyury (BTBR) Obez Farelerde Üreme, Metabolik ve Böbrek Eksikliklerini Düzeltmeye Yönelik Bir Yaklaşım (Video) | JoVE Journal

Beyaz ve Kahverengi Yağ Greftleri: Siyah ve Ten Rengi Brachyury (BTBR) Obez Farelerde Üreme, Metabolik ve Böbrek Eksikliklerini Düzeltmeye Yönelik Bir Yaklaşım

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