An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice
An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice
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DOI：
10.1152/ajpendo.00075.2010
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发表时间：
2010-11-01
影响因子：
5.1
通讯作者：
Araki, Eiichi
中科院分区：
文献类型：
--
作者：
Adachi, Hironori;Kondo, Tatsuya;Araki, Eiichi
阿达奇H，近藤T，小川R，Sasaki K，Morino-Koga S，Sakakida M，Kawashima J，Motoshima H，Furukawa N，Tsuruzoe K，Miyamura N，Kai H，荒木E.一种非环聚类异戊二烯衍生物，香叶基香叶基丙酮可防止高脂喂养小鼠内脏肥胖和胰岛素抵抗。Am J Physiol Endocrinol Metab 299：E764-E771，2010年。首次发表于2010年8月17日; doi：10.1152/ajpendo.00075.2010.-诱导热休克蛋白（HSP）72改善糖尿病动物模型的胰岛素抵抗和肥胖。香叶基香叶基丙酮（GGA），被称为抗溃疡药物，诱导HSP 72和保护器官免受几种细胞应激。本研究探讨了GGA给药是否会诱导小鼠肝脏中的HSP 72，并对高脂喂养产生生理保护作用。在喂食高脂饲料（HFD）的小鼠中进行单次口服200 mg/kg GGA，为期4周。评估了与胰岛素信号传导相关的代谢参数、细胞因子和基因表达。单次给药GGA可诱导正常饲料喂养和HFD喂养小鼠肝脏中的HSP 72。HFD后胰岛素抵抗略有改善。四周的GGA给药也增加了肝脏中的HSP 72，并显着改善胰岛素抵抗和葡萄糖稳态葡萄糖挑战。在HFD小鼠的肝脏中，c-jun NH 2-末端激酶（JNK）的活化被减弱，胰岛素信号被改善。内脏脂肪减少GGA治疗的小鼠，伴随着减少瘦素和增加脂联素水平。GGA可以通过改善胰岛素信号传导和减少肥胖而成为治疗代谢综合征以及2型糖尿病的新治疗方法。GGA的这些有益作用可以通过诱导肝脏中的HSP 72和JNK失活来介导。
Adachi H, Kondo T, Ogawa R, Sasaki K, Morino-Koga S, Sakakida M, Kawashima J, Motoshima H, Furukawa N, Tsuruzoe K, Miyamura N, Kai H, Araki E. An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice. Am J Physiol Endocrinol Metab 299: E764-E771, 2010. First published August 17, 2010; doi: 10.1152/ajpendo.00075.2010.-Induction of heat shock protein (HSP) 72 improves insulin resistance and obesity in diabetic animal models. Geranylgeranylacetone (GGA), known as an antiulcer drug, induces HSP72 and protects organs against several cellular stresses. This study investigated whether GGA administration would induce HSP72 in liver and render physiological protection against high-fat feeding in mice. A single and 4-wk oral administration of 200 mg/kg GGA was performed in high-fat diet (HFD)-fed mice. Metabolic parameters, cytokines, and gene expressions related to insulin signaling were evaluated. A single administration of GGA induced HSP72 in liver of normal chow-fed and HFD-fed mice. Insulin resistance after HFD was slightly ameliorated. Four weeks of GGA administration also increased HSP72 in liver and significantly improved insulin resistance and glucose homeostasis upon glucose challenge. Activation of c-jun NH2-terminal kinase (JNK) was attenuated, and insulin signaling was improved in the liver of HFD mice. Visceral adiposity was decreased in GGA-treated mice, accompanied by reduced leptin and increased adiponectin levels. GGA can be a novel therapeutic approach to treat metabolic syndrome as well as type 2 diabetes by improving insulin signaling and reducing adiposity. These beneficial effects of GGA could be mediated through HSP72 induction and JNK inactivation in the liver.