Obesity-associated family with sequence similarity 13, member A (FAM13A) is dispensable for adipose development and insulin sensitivity.

Obesity-associated family with sequence similarity 13, member A (FAM13A) is dispensable for adipose development and insulin sensitivity.
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DOI:
10.1038/s41366-018-0222-y
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发表时间:
2019-06
期刊:
International journal of obesity (2005)
影响因子:
--
通讯作者:
Chen W
Chen W
中科院分区:
其他
文献类型:
--
作者:
Tang J;Zhou H;Sahay K;Xu W;Yang J;Zhang W;Chen W

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肥胖症及其相关的疾病是世界范围内最主要和最迅速蔓延的健康流行病。最近的全基因组关联研究(GWAS)显示,序列相似性13家族成员A(FAM13A)基因的单核苷酸多态性(SNP)变异与校正体重指数(BMI)后的腰臀比(WHR)(WHRadjBMI)密切相关。然而,FAM13A在脂肪发育和肥胖症中的功能在很大程度上仍未被表征。使用瘦型、遗传性肥胖和高脂饮食诱导的肥胖(DIO)动物模型和在脂肪细胞分化期间研究脂肪组织库中FAM13 A的表达。使用FAM13A功能获得和丧失的基质血管细胞(SVC)或3T3-L1细胞来确定FAM13A在调节脂肪细胞分化中的参与。Fam13a −/−小鼠的脂肪发育和代谢稳态在正常饲料和高脂肪饲料喂养下进行表征。在遗传和饮食诱导的肥胖症中,小鼠FAM13 A的表达受到营养调节,并且在附睾和皮下脂肪中显著降低。其表达在成熟脂肪细胞中富集,并可能通过过氧化物酶体增殖物激活受体-γ(PPAR γ)依赖性机制在小鼠和人脂肪形成过程中显著上调。然而,Fam13a −/−小鼠仅表现出更高的肥胖倾向,并且没有受到DIO和胰岛素抵抗的保护。虽然Fam13a −/− SVC维持正常的脂肪生成,但3T3-L1前脂肪细胞中FAM13A的过表达下调β-连环蛋白信号传导,并使前脂肪细胞更容易凋亡。此外,FAM13A过表达在很大程度上阻断了由标准激素鸡尾酒诱导的脂肪形成,但在分化的早期阶段加入PPAR γ激动剂吡格列酮可以部分挽救脂肪形成。我们的研究结果表明,FAM13A是脂肪发育和胰岛素敏感性。然而,FAM13A的表达需要在脂肪前体细胞中严格控制,以使其正常存活和下游脂肪形成。这些数据为FAM13A与肥胖之间的联系提供了新的见解。
Obesity and its associated morbidities represent the major and most rapidly expanding world-wide health epidemic. Recent genome-wide association studies (GWAS) reveal that single nucleotide polymorphism (SNP) variant in the Family with Sequence Similarity 13, Member A (FAM13A) gene is strongly associated with waist–hip ratio (WHR) with adjustment for body mass index (BMI) (WHRadjBMI). However, the function of FAM13A in adipose development and obesity remains largely uncharacterized. The expression of FAM13A in adipose tissue depots were investigated using lean, genetic obese and high fat diet-induced obese (DIO) animal models and during adipocyte differentiation. Stromal vascular cells (SVCs) or 3T3-L1 cells with gain and loss of function of FAM13A were used to determine the involvement of FAM13A in regulating adipocyte differentiation. Adipose development and metabolic homeostasis in Fam13a−/− mice were characterized under normal chow and high fat diet feeding. Murine FAM13A expression was nutritionally regulated and dramatically reduced in epididymal and subcutaneous fat in genetic and diet-induced obesity. Its expression was enriched in mature adipocytes and significantly upregulated during murine and human adipogenesis potentially through a peroxisome proliferator-activated receptor-gamma (PPARγ)-dependent mechanism. However, Fam13a−/− mice only exhibited a tendency of higher adiposity and were not protected from DIO and insulin resistance. While Fam13a−/− SVCs maintained normal adipogenesis, overexpression of FAM13A in 3T3-L1 preadipocytes downregulated β-catenin signaling and rendered preadipocytes more susceptible to apoptosis. Moreover, FAM13A overexpression largely blocked adipogenesis induced by a standard hormone cocktail, but adipogenesis can be partially rescued by the addition of PPARγ agonist pioglitazone at an early stage of differentiation. Our results suggest that FAM13A is dispensable for adipose development and insulin sensitivity. Yet the expression of FAM13A needs to be tightly controlled in adipose precursor cells for their proper survival and downstream adipogenesis. These data provide novel insights into the link between FAM13A and obesity.
DOI: 10.1038/ng.2609
发表时间: 2013-06
期刊: NATURE GENETICS
影响因子: 30.8
作者:
Fingerlin, Tasha E.;Murphy, Elissa;Zhang, Weiming;Peljto, Anna L.;Brown, Kevin K.;Steele, Mark P.;Loyd, James E.;Cosgrove, Gregory P.;Lynch, David;Groshong, Steve;Collard, Harold R.;Wolters, Paul J.;Bradford, Williamson Z.;Kossen, Karl;Seiwert, Scott D.;du Bois, Roland M.;Garcia, Christine Kim;Devine, Megan S.;Gudmundsson, Gunnar;Isaksson, Helgi J.;Kaminski, Naftali;Zhang, Yingze;Gibson, Kevin F.;Lancaster, Lisa H.;Cogan, Joy D.;Mason, Wendi R.;Maher, Toby M.;Molyneaux, Philip L.;Wells, Athol U.;Moffatt, Miriam F.;Selman, Moises;Pardo, Annie;Kim, Dong Soon;Crapo, James D.;Make, Barry J.;Regan, Elizabeth A.;Walek, Dinesha S.;Daniel, Jerry J.;Kamatani, Yoichiro;Zelenika, Diana;Smith, Keith;McKean, David;Pedersen, Brent S.;Talbert, Janet;Kidd, Raven N.;Markin, Cheryl R.;Beckman, Kenneth B.;Lathrop, Mark;Schwarz, Marvin I.;Schwartz, David A.
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发表时间: 2015-02-12
期刊: NATURE
影响因子: 64.8
作者:
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发表时间: 2016-07-15
影响因子: 24.7
作者:
Jiang, Zhiqiang;Lao, Taotao;Zhou, Xiaobo
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发表时间: 2015-02-12
期刊: NATURE
影响因子: 64.8
作者:
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Warwick;de Craen, Anton J. M.;Delgado, Graciela;Dimitriou, Maria;Doney, Alex S. 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B.;Dorajoo, Rajkumar;Reinmaa, Eva;Salem, Rany M.;Sandholm, Niina;Scott, Robert A.;Stolk, Lisette;Takahashi, Atsushi;Tanaka, Toshihiro;van 't Hooft, Ferdinand M.;Vinkhuyzen, Anna A. E.;Westra, Harm-Jan;Zheng, Wei;Zondervan, Krina T.;Heath, Andrew C.;Arveiler, Dominique;Bakker, Stephan J. L.;Beilby, John;Bergman, Richard N.;Blangero, John;Bovet, Pascal;Campbell, Harry;Caulfield, Mark J.;Cesana, Giancarlo;Chakravarti, Aravinda;Chasman, Daniel I.;Chines, Peter S.;Collins, Francis S.;Crawford, Dana C.;Cupples, L. Adrienne;Cusi, Daniele;Danesh, John;de Faire, Ulf;den Ruijter, Hester M.;Dominiczak, Anna F.;Erbel, Raimund;Erdmann, Jeanette;Eriksson, Johan G.;Farrall, Martin;Felix, Stephan B.;Ferrannini, Ele;Ferrieres, Jean;Ford, Ian;Forouhi, Nita G.;Forrester, Terrence;Franco, Oscar H.;Gansevoort, Ron T.;Gejman, Pablo V.;Gieger, Christian;Gottesman, Omri;Gudnason, Vilmundur;Gyllensten, Ulf;Hall, Alistair S.;Harris, Tamara B.;Hattersley, Andrew T.;Hicks, Andrew A.;Hindorff, Lucia A.;Hingorani, Aroon D.;Hofman, Albert;Homuth, Georg;Hovingh, G. Kees;Humphries, Steve E.;Hunt, Steven C.;Hypponen, Elina;Illig, Thomas;Jacobs, Kevin B.;Jarvelin, Marjo-Riitta;Joeckel, Karl-Heinz;Johansen, Berit;Jousilahti, Pekka;Jukema, J. Wouter;Jula, Antti M.;Kaprio, Jaakko;Kastelein, John J. P.;Keinanen-Kiukaanniemi, Sirkka M.;Kiemeney, Lambertus A.;Knekt, Paul;Kooner, Jaspal S.;Kooperberg, Charles;Kovacs, Peter;Kraja, Aldi T.;Kumari, Meena;Kuusisto, Johanna;Lakka, Timo A.;Langenberg, Claudia;Le Marchand, Laic;Lehtimaki, Terho;Lyssenko, Valeriya;Mannisto, Satu;Marette, Andre;Matise, Tara C.;McKenzie, Colin A.;McKnight, Barbara;Moll, Frans L.;Morris, Andrew D.;Morris, Andrew P.;Murray, Jeffrey C.;Nelis, Mari;Ohlsson, Claes;Oldehinkel, Albertine J.;Ong, Ken K.;Madden, Pamela A. F.;Pasterkamp, Gerard;Peden, John F.;Peters, Annette;Postma, Dirkje S.;Pramstaller, Peter P.;Price, Jackie F.;Qi, Lu;Raitakari, Olli T.;Rankinen, Tuomo;Rao, D. C.;Rice, Treva K.;Ridker, Paul M.;Rioux, John D.;Ritchie, Marylyn D.;Rudan, Igor;Salomaa, Veikko;Samani, Nilesh J.;Saramines, Jouko;Sarzynski, Mark A.;Schunkert, Heribert;Schwarz, Peter E. H.;Sever, Peter;Shuldiner, Alan R.;Sinisalo, Juha;Stolk, Ronald P.;Strauch, Konstantin;Toenjes, Anke;Tregouet, David-Alexandre;Tremblay, Angelo;Tremoli, Elena;Virtamo, Jarmo;Vohl, Marie-Claude;Voelker, Uwe;Waeber, Gerard;Willemsen, Gonneke;Witteman, Jacqueline C.;Zillikens, M. Carola;Adair, Linda S.;Amouyel, Philippe;Asselbergs, Folkert W.;Assimes, Themistocles L.;Bochud, Murielle;Boehm, Bernhard O.;Boerwinkle, Eric;Bornstein, Stefan R.;Bottinger, Erwin P.;Bouchard, Claude;Cauchi, Stephane;Chambers, John C.;Chanock, Stephen J.;Cooper, Richard S.;de Bakker, Paul I. W.;Dedoussis, George;Ferrucci, Luigi;Franks, Paul W.;Froguel, Philippe;Groop, Leif C.;Haiman, Christopher A.;Hamsten, Anders;Hui, Jennie;Hunter, David J.;Hveem, Kristian;Kaplan, Robert C.;Kivimaki, Mika;Kuh, Diana;Laakso, Markku;Liu, Yongmei;Martin, Nicholas G.;Maerz, Winfried;Melbve, Mads;Metspalu, Andres;Moebus, Susanne;Munroe, Patricia B.;Njolstad, Inger;Oostra, Ben A.;Palmer, Colin N. A.;Pedersen, Nancy L.;Perola, Markus;Perusse, Louis;Peters, Ulrike;Power, Chris;Quertermous, Thomas;Rauramaa, Rainer;Rivadeneira, Fernando;Saaristo, Timo E.;Saleheen, Danish;Sattar, Naveed;Schadt, Eric E.;Schlessinger, David;Slagboom, P. Eline;Snieder, Harold;Spector, Tim D.;Thorsteinsdottir, Unnu R.;Stumvoll, Michael;Tuomilehto, Jaakko;Uitterlinden, Andre G.;Uusitupa, Matti;van der Harst, Pim;Walker, Mark;Wallaschofski, Henri;Wareham, Nicholas J.;Watkins, Hugh;Weir, David R.;Wichmann, H-Erich;Wilson, James F.;Zanen, Pieter;Borecki, Ingrid B.;Deloukas, Panos;Fox, Caroline S.;Heid, Iris M.;O'Connell, Jeffrey R.;Strachan, David P.;Stefansson, Kari;van Duijri, Cornelia M.;Abecasis, Goncalo R.;Franke, Lude;Frayling, Timothy M.;McCarthy, Mark I.;Visscher, Peter M.;Scherag, Andre;Willer, Cristen J.;Boehnke, Michael;Mohlke, Karen L.;Lindgren, Cecilia M.;Beckmann, Jacques S.;Barroso, Ines;North, Kari E.;Ingelsson, Erik;Hirschhorn, Joel N.;Loos, Ruth J. F.;Speliotes, Elizabeth K.
通讯作者: Speliotes, Elizabeth K.