Involvement of SIK3 in glucose and lipid homeostasis in mice.
Involvement of SIK3 in glucose and lipid homeostasis in mice.
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DOI：
10.1371/journal.pone.0037803
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Takemori H
中科院分区：
文献类型：
--
作者：
Uebi T;Itoh Y;Hatano O;Kumagai A;Sanosaka M;Sasaki T;Sasagawa S;Doi J;Tatsumi K;Mitamura K;Morii E;Aozasa K;Kawamura T;Okumura M;Nakae J;Takikawa H;Fukusato T;Koura M;Nish M;Hamsten A;Silveira A;Bertorello AM;Kitagawa K;Nagaoka Y;Kawahara H;Tomonaga T;Naka T;Ikegawa S;Tsumaki N;Matsuda J;Takemori H
盐诱导蛋白激酶3(SIK3)是一种AMP激活的蛋白激酶相关蛋白，在摄入了富含脂肪、蔗糖和胆固醇的饮食后，在小鼠的肝脏中被诱导。为了研究SIK3是否可以调节肝脏中的葡萄糖和脂肪代谢，我们分析了SIK3缺陷小鼠的表型。SIK3−/−小鼠具有营养不良的表型(即脂营养不良、低脂血症、低血糖和高胰岛素敏感性)，并伴有胆汁淤积和胆石症。低血糖和高胰岛素敏感的表型可能是由于能量储存的减少，这表现为肝脏中脂肪酸合成途径部分的低表达水平。SIK3−/−小鼠的胆道疾病与基因表达程序的失调有关，该程序对营养压力做出反应，并可能受到核受体的调节。维甲酸在胆固醇和胆汁酸的动态平衡中起作用，而产生维甲酸的ALDH1a在SIK3−/−小鼠中低水平表达。9-顺式维甲酸治疗可改善SIK3-−/−小鼠的脂代谢紊乱。总之，SIK3是一种新的能量调节剂，通过与维甲酸代谢偶联来调节胆固醇和胆汁酸代谢，并可能改变小鼠的能量储存大小。
Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3 −/− mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3 −/− mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3 −/− mice. Lipid metabolism disorders in Sik3 −/− mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice.
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DOI：
10.1073/pnas.1008859107
发表时间：
2010-12-14
影响因子：
11.1
作者：
Kane, Maureen A.;Folias, Alexandra E.;Napoli, Joseph L.
通讯作者：
Napoli, Joseph L.
影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
DOI：
10.1038/nrm3072
发表时间：
2011-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.1932773100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Iourgenko, V;Zhang, WJ;Labow, MA
通讯作者：
Labow, MA
影响因子：
4.1
作者：
Kok, T;Bloks, VW;Kuipers, F
通讯作者：
Kuipers, F