Temporal relationship between diet-induced steatosis and onset of insulin/leptin resistance in male Wistar rats.
Temporal relationship between diet-induced steatosis and onset of insulin/leptin resistance in male Wistar rats.
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DOI：
10.1371/journal.pone.0117008
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yao Z
中科院分区：
文献类型：
--
作者：
Zhang L;Song H;Ge Y;Ji G;Yao Z
已知喂食高脂高糖（HFHS）饮食的大鼠会出现代谢综合征，包括高胰岛素血症、高瘦素血症、高血糖症、糖尿病血脂异常和肝脏脂肪变性。本研究的目的是确定雄性Wistar大鼠（6周龄）喂食食物或HFHS饮食长达8周后，肝脂肪变性的发展与下丘脑和肝脏中胰岛素和瘦素抵抗的发生之间的时间关系。定量空腹血糖、脂质/脂蛋白、胰岛素和瘦素水平，评估肝脂肪变性和炎症的组织病理学评分，并分析负责脂肪生成和脂肪生成的胰岛素和瘦素信号传导的常见检查点的反应。此外，在HFHS节食的不同阶段进行急性胰岛素或瘦素给药，以确定相应信号通路的响应性。高胰岛素血症、高血糖症、血脂异常和基础胰岛素抵抗的稳态模型评估增加发生在HFHS饮食后1周，与下丘脑和肝脏中细胞因子信号传导抑制因子3的上调一致。然而，脂肪肝，伴随着增加的表达固醇调节元件结合蛋白1c和磷酸烯醇丙酮酸羧激酶，没有表现出，直到4- 8周后HFHS饮食。在肝脏和下丘脑中，胰岛素敏感性降低（表现为胰岛素受体底物1和蛋白激酶B磷酸化降低）发生在瘦素抵抗（表现为信号转导和转录激活因子3活化受损）之前约2周。急性胰岛素/瘦素给药也表现出受损的胰岛素或瘦素信号转导。这些数据表明，在喂食HFHS饮食的大鼠中，胰岛素敏感性和瘦素抵抗的降低至少比肝脂肪变性的表现早2-3周发生。
Rats fed with high-fat-high-sucrose (HFHS) diet are known to manifest metabolic syndrome including hyperinsulinemia, hyperleptinemia, hyperglycemia, diabetic dyslipidemia, and hepatic steatosis. The aim of the current study is to determine the temporal relationships between the development of hepatic steatosis and the onset of insulin and leptin resistance in hypothalamus and liver in male Wistar rats (six weeks of age) fed chow or HFHS diet for up to 8 weeks. Fasting plasma glucose, lipids/lipoproteins, insulin and leptin levels were quantified, histopathologic score of hepatic steatosis and inflammation were assessed, and the responses of common checkpoints of insulin and leptin signalling responsible for lipogenesis and gluconeogenesis were analyzed. In addition, acute insulin or leptin administration was performed at different stages of HFHS dieting to determine the responsiveness of the respective signalling pathways. Hyperinsulinemia, hyperglycemia, dyslipidemia, and increased homeostasis model assessment of basal insulin resistance occurred 1-week after HFHS dieting, coinciding with upregulation of suppressor of cytokine signalling 3 in both hypothalamus and liver. However, hepatosteatosis, accompanied with increased expression of sterol regulatory element binding protein 1c and phosphoenolpyruvate carboxykinase, did not manifest until 4- to 8-week after HFHS dieting. Lowered insulin sensitivity (shown by decreased insulin receptor substrate 1 and protein kinase B phosphorylation) occurred approximately 2 weeks prior to leptin resistance (shown by impaired signal transducer and activator of transcription 3 activation) in both the liver and hypothalamus. Acute insulin/leptin administration also demonstrated the impaired insulin or leptin signalling transduction. These data suggest that lowered insulin sensitivity and leptin resistance occurred at least 2–3 weeks earlier than the manifestation of hepatosteatosis in rats fed HFHS diet.
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影响因子：
3.7
作者：
Guo J;Jou W;Gavrilova O;Hall KD
通讯作者：
Hall KD
影响因子：
7.7
作者：
Huynh FK;Levi J;Denroche HC;Gray SL;Voshol PJ;Neumann UH;Speck M;Chua SC;Covey SD;Kieffer TJ
通讯作者：
Kieffer TJ
影响因子：
5.3
作者：
Hübschle, T;Thom, E;Meyerhof, W
通讯作者：
Meyerhof, W
影响因子：
3.9
作者：
Kim, In Kyoung;Kim, Jihye;Song, Jihyun
通讯作者：
Song, Jihyun
DOI：
10.1155/2014/409547
发表时间：
2014
期刊：
ISRN veterinary science
影响因子：
--
作者：
Lacombe VA
通讯作者：
Lacombe VA