MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis.
MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis.
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DOI：
10.1016/j.jlr.2023.100349
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发表时间：
2023-04
影响因子：
6.5
通讯作者：
Brown, J. Mark
中科院分区：
文献类型：
--
作者：
Massey, William J.;Varadharajan, Venkateshwari;Banerjee, Rakhee;Brown, Amanda L.;Horak, Anthony J.;Hohe, Rachel C.;Jung, Bryan M.;Qiu, Yunguang;Chan, E. Ricky;Pan, Calvin;Zhang, Renliang;Allende, Daniela S.;Willard, Belinda;Cheng, Feixiong;Lusis, Aldons J.;Brown, J. Mark
我们之前已经证明，反义寡核苷酸介导的Mboat7（编码膜结合o -酰基转移酶7的基因）在小鼠肝脏和脂肪组织中的敲低可促进高脂肪饮食诱导的肝脂肪变性、高胰岛素血症和全身胰岛素抵抗。此后，其他研究小组发现，肝细胞特异性基因缺失Mboat7促进了小鼠显著脂肪肝和NAFLD的进展，但不改变胰岛素敏感性，提示细胞自主作用的潜力。在这里，我们发现MBOAT7在脂肪细胞中的功能有助于饮食诱导的代谢紊乱，包括高胰岛素血症和全身胰岛素抵抗。在白蛋白启动子和脂联素启动子的控制下，我们分别使用Cre-recombinase小鼠产生Mboat7基因敲除小鼠和肝细胞特异性Mboat7基因敲除小鼠。在这里，我们发现MBOAT7在脂肪细胞中的功能有助于饮食诱导的代谢紊乱，包括高胰岛素血症和全身胰岛素抵抗。Mboat7在白色脂肪组织中的表达与饮食诱导的肥胖密切相关，研究人员对约100只饲喂高脂肪/高蔗糖饮食的近交系小鼠进行了研究。此外，我们发现脂肪细胞特异性Mboat7基因缺失足以促进高胰岛素血症、全身性胰岛素抵抗和轻度脂肪肝。与肝脏不同，Mboat7在维持含有花生四烯酸的PI池中发挥相对较小的作用，而Mboat7是脂肪组织中含有花生四烯酸的PI池的主要来源。我们的数据表明，MBOAT7是脂肪组织PI稳态的关键调节因子，脂肪细胞MBOAT7驱动的PI生物合成与小鼠高胰岛素血症和胰岛素抵抗密切相关。
We previously demonstrated that antisense oligonucleotide-mediated knockdown of Mboat7, the gene encoding membrane bound O-acyltransferase 7, in the liver and adipose tissue of mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance. Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression in mice but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. We generated Mboat7 floxed mice and created hepatocyte- and adipocyte-specific Mboat7 knockout mice using Cre-recombinase mice under the control of the albumin and adiponectin promoter, respectively. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ∼100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, we found that adipocyte-specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid-containing PI pools, Mboat7 is the major source of arachidonic acid-containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice.
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影响因子：
3.3
作者：
Lee HC;Inoue T;Sasaki J;Kubo T;Matsuda S;Nakasaki Y;Hattori M;Tanaka F;Udagawa O;Kono N;Itoh T;Ogiso H;Taguchi R;Arita M;Sasaki T;Arai H
通讯作者：
Arai H
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
在四种常用的近交小鼠菌株中的体内葡萄糖代谢。
影响因子：
7.7
作者：
Berglund, Eric D.;Li, Candice Y.;Poffenberger, Greg;Ayala, Julio E.;Fueger, Patrick T.;Willis, Shannon E.;Jewell, Marybeth M.;Powers, Alvin C.;Wasserman, David H.
通讯作者：
Wasserman, David H.
影响因子：
6.5
作者：
Brown, J. Mark;Betters, Jenna L.;Yu, Liqing
通讯作者：
Yu, Liqing
影响因子：
4.8
作者：
Gijon, Miguel A.;Riekhof, Wayne R.;Voelker, Dennis R.
通讯作者：
Voelker, Dennis R.