A gain-of-function mutation in adenylate cyclase 3 protects mice from diet-induced obesity.
A gain-of-function mutation in adenylate cyclase 3 protects mice from diet-induced obesity.
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DOI：
10.1371/journal.pone.0110226
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gekakis N
中科院分区：
文献类型：
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作者：
Pitman JL;Wheeler MC;Lloyd DJ;Walker JR;Glynne RJ;Gekakis N
在筛选影响高脂饮食(HFD)代谢反应的基因时，我们选择了一种N-乙基-N-亚硝脲(ENU)诱变的小鼠品系JLL，该品系对饮食诱导的肥胖(DIO)具有明显的遗传抗性。与未受影响的对照组相比，突变的动物显著降低了体重和脂肪质量，并降低了基础胰岛素和血糖水平。白色脂肪组织(Wat)和棕色脂肪组织(BAT)在突变动物中的储存量都较小。饲喂高脂饲料的突变动物仅比饲喂普通食物的动物体重略高，并可防止肝脏脂肪堆积。表型与12号染色体上5.7-Mb的区间有关，对整个区间的测序发现了一个单一的编码突变，预测会导致Adcy3蛋白(Adcy3M279I，以下称为Adcy3Jll)第279位的蛋氨酸到异亮氨酸的替换。突变的蛋白质是高度活跃的，可能是结构性的，在基于细胞的分析中产生高水平的环磷酸腺苷。这些小鼠证明，Adcy3活性的增加有力地保护了动物免受饮食诱导的代谢紊乱的影响。
In a screen for genes that affect the metabolic response to high-fat diet (HFD), we selected one line of N-ethyl-N-nitrosourea (ENU)-mutagenized mice, Jll, with dominantly inherited resistance to diet-induced obesity (DIO). Mutant animals had dramatically reduced body weight and fat mass, and low basal insulin and glucose levels relative to unaffected controls. Both white adipose tissue (WAT) and brown adipose tissue (BAT) depots were smaller in mutant animals. Mutant animals fed a HFD gained only slightly more weight than animals fed regular chow, and were protected from hepatic lipid accumulation. The phenotype was genetically linked to a 5.7-Mb interval on chromosome 12, and sequencing of the entire interval identified a single coding mutation, predicted to cause a methionine-to-isoleucine substitution at position 279 of the Adcy3 protein (Adcy3M279I, henceforth referred to as Adcy3Jll). The mutant protein is hyperactive, possibly constitutively so, producing elevated levels of cyclic AMP in a cell-based assay. These mice demonstrate that increased Adcy3 activity robustly protect animals from diet-induced metabolic derangements.
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影响因子：
30.8
作者：
通讯作者：
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Sec61alpha1中的一个点突变导致小鼠糖尿病和肝脏tososisosis。
影响因子：
7.7
作者：
Lloyd DJ;Wheeler MC;Gekakis N
通讯作者：
Gekakis N
影响因子：
30.8
作者：
Monda, Keri L.;Chen, Gary K.;Taylor, Kira C.;Palmer, Cameron;Edwards, Todd L.;Lange, Leslie A.;Ng, Maggie C. Y.;Adeyemo, Adebowale A.;Allison, Matthew A.;Bielak, Lawrence F.;Chen, Guanjie;Graff, Mariaelisa;Irvin, Marguerite R.;Rhie, Suhn K.;Li, Guo;Liu, Yongmei;Liu, Youfang;Lu, Yingchang;Nalls, Michael A.;Sun, Yan V.;Wojczynski, Mary K.;Yanek, Lisa R.;Aldrich, Melinda C.;Ademola, Adeyinka;Amos, Christopher I.;Bandera, Elisa V.;Bock, Cathryn H.;Britton, Angela;Broeckel, Ulrich;Cai, Quiyin;Caporaso, Neil E.;Carlson, Chris S.;Carpten, John;Casey, Graham;Chen, Wei-Min;Chen, Fang;Chen, Yii-Der I.;Chiang, Charleston W. K.;Coetzee, Gerhard A.;Demerath, Ellen;Deming-Halverson, Sandra L.;Driver, Ryan W.;Dubbert, Patricia;Feitosa, Mary F.;Feng, Ye;Freedman, Barry I.;Gillanders, Elizabeth M.;Gottesman, Omri;Guo, Xiuqing;Haritunians, Talin;Harris, Tamara;Harris, Curtis C.;Hennis, Anselm J. M.;Hernandez, Dena G.;McNeill, Lorna H.;Howard, Timothy D.;Howard, Barbara V.;Howard, Virginia J.;Johnson, Karen C.;Kang, Sun J.;Keating, Brendan J.;Kolb, Suzanne;Kuller, Lewis H.;Kutlar, Abdullah;Langefeld, Carl D.;Lettre, Guillaume;Lohman, Kurt;Lotay, Vaneet;Lyon, Helen;Manson, Joann E.;Maixner, William;Meng, Yan A.;Monroe, Kristine R.;Morhason-Bello, Imran;Murphy, Adam B.;Mychaleckyj, Josyf C.;Nadukuru, Rajiv;Nathanson, Katherine L.;Nayak, Uma;N'Diaye, Amidou;Nemesure, Barbara;Wu, Suh-Yuh;Leske, M. Cristina;Neslund-Dudas, Christine;Neuhouser, Marian;Nyante, Sarah;Ochs-Balcom, Heather;Ogunniyi, Adesola;Ogundiran, Temidayo O.;Ojengbede, Oladosu;Olopade, Olufunmilayo I.;Palmer, Julie R.;Ruiz-Narvaez, Edward A.;Palmer, Nicholette D.;Press, Michael F.;Rampersaud, Evandine;Rasmussen-Torvik, Laura J.;Rodriguez-Gil, Jorge L.;Salako, Babatunde;Schadt, Eric E.;Schwartz, Ann G.;Shriner, Daniel A.;Siscovick, David;Smith, Shad B.;Wassertheil-Smoller, Sylvia;Speliotes, Elizabeth K.;Spitz, Margaret R.;Sucheston, Lara;Taylor, Herman;Tayo, Bamidele O.;Tucker, Margaret A.;Van Den Berg, David J.;Edwards, Digna R. Velez;Wang, Zhaoming;Wiencke, John K.;Winkler, Thomas W.;Witte, John S.;Wrensch, Margaret;Wu, Xifeng;Yang, James J.;Levin, Albert M.;Young, Taylor R.;Zakai, Neil A.;Cushman, Mary;Zanetti, Krista A.;Zhao, Jing Hua;Zhao, Wei;Zheng, Yonglan;Zhou, Jie;Ziegler, Regina G.;Zmuda, Joseph M.;Fernandes, Jyotika K.;Gilkeson, Gary S.;Kamen, Diane L.;Hunt, Kelly J.;Spruill, Ida J.;Ambrosone, Christine B.;Ambs, Stefan;Arnett, Donna K.;Atwood, Larry;Becker, Diane M.;Berndt, Sonja I.;Bernstein, Leslie;Blot, William J.;Borecki, Ingrid B.;Bottinger, Erwin P.;Bowden, Donald W.;Burke, Gregory;Chanock, Stephen J.;Cooper, Richard S.;Ding, Jingzhong;Duggan, David;Evans, Michele K.;Fox, Caroline;Garvey, W. Timothy;Bradfield, Jonathan P.;Hakonarson, Hakon;Grant, Struan F. A.;Hsing, Ann;Chu, Lisa;Hu, Jennifer J.;Huo, Dezheng;Ingles, Sue A.;John, Esther M.;Jordan, Joanne M.;Kabagambe, Edmond K.;Kardia, Sharon L. R.;Kittles, Rick A.;Goodman, Phyllis J.;Klein, Eric A.;Kolonel, Laurence N.;Le Marchand, Loic;Liu, Simin;McKnight, Barbara;Millikan, Robert C.;Mosley, Thomas H.;Padhukasahasram, Badri;Williams, L. Keoki;Patel, Sanjay R.;Peters, Ulrike;Pettaway, Curtis A.;Peyser, Patricia A.;Psaty, Bruce M.;Redline, Susan;Rotimi, Charles N.;Rybicki, Benjamin A.;Sale, Michele M.;Schreiner, Pamela J.;Signorello, Lisa B.;Singleton, Andrew B.;Stanford, Janet L.;Strom, Sara S.;Thun, Michael J.;Vitolins, Mara;Zheng, Wei;Moore, Jason H.;Williams, Scott M.;Ketkar, Shamika;Zhu, Xiaofeng;Zonderman, Alan B.;Kooperberg, Charles;Papanicolaou, George J.;Henderson, Brian E.;Reiner, Alex P.;Hirschhorn, Joel N.;Loos, Ruth J. F.;North, Kari E.;Haiman, Christopher A.
通讯作者：
Haiman, Christopher A.
影响因子：
82.9
作者：
Altarejos, Judith Y.;Goebel, Naomi;Conkright, Michael D.;Inotiel, Hiroshi;Xie, Jianxin;Arias, Carlos M.;Sawchenko, Paul E.;Montminy, Marc
通讯作者：
Montminy, Marc
影响因子：
64.8
作者：
通讯作者：
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