The carbohydrate-insulin model does not explain the impact of varying dietary macronutrients on the body weight and adiposity of mice
The carbohydrate-insulin model does not explain the impact of varying dietary macronutrients on the body weight and adiposity of mice
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DOI：
10.1016/j.molmet.2019.11.010
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发表时间：
2020-02-01
影响因子：
8.1
通讯作者：
Speakman, John R.
中科院分区：
文献类型：
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作者：
Hu, Sumei;Wang, Lu;Speakman, John R.
目的：碳水化合物-胰岛素模型(CIM)预测，由于膳食碳水化合物的增加，空腹和餐后胰岛素会刺激能量摄入，降低能量消耗，导致能量正平衡和体重增加。本研究的目的是用C57BL/6小鼠直接验证CIM的预测。方法：通过改变饮食中固定蛋白质或脂肪含量的碳水化合物来设计饮食，并急性或长期给予C57BL/6小鼠12周。测量小鼠的体重、体成分、食物摄入量和能量消耗。他们的空腹和餐后血糖和胰岛素水平也被测量。对下丘脑和皮下白色脂肪组织的RNA进行RNA-SEQ。使用IPA进行通径分析。结果：只有餐后胰岛素和空腹血糖水平符合CIM的预测。SWAT中的脂解和瘦素信号通路受到抑制，与空腹胰岛素升高有关，支持CIM预测的高胰岛素影响。然而，由于较高的空腹胰岛素与碳水化合物摄入量无关，总体模式不支持该模型。此外，随着空腹胰岛素的增加，下丘脑饥饿通路受到抑制，能量摄入没有增加。在较高的胰岛素水平下，SWAT中的褐变途径被抑制，但每日能量消耗没有改变。结论：其中两个预测部分支持(因此也部分不支持)，其他三个预测不支持。我们的结论是，CIM没有解释饮食中大量营养素对小鼠肥胖的影响。(C)2019年提交人。由Elsevier GmbH出版。
Objectives: The carbohydrate-insulin model (CIM) predicts that increases in fasting and post-prandial insulin in response to dietary carbohydrates stimulate energy intake and lower energy expenditures, leading to positive energy balance and weight gain. The objective of the present study was to directly test the CIM's predictions using C57BL/6 mice.Methods: Diets were designed by altering dietary carbohydrates with either fixed protein or fat content and were fed to C57BL/6 mice acutely or chronically for 12 weeks. The body weight, body composition, food intake, and energy expenditures of the mice were measured. Their fasting and post-prandial glucose and insulin levels were also measured. RNA-seq was performed on RNA from the hypothalamus and subcutaneous white adipose tissue. Pathway analysis was conducted using IPA.Results: Only the post-prandial insulin and fasting glucose levels followed the CIM's predictions. The lipolysis and leptin signaling pathways in the sWAT were inhibited in relation to the elevated fasting insulin, supporting the CIM's predicted impact of high insulin. However, because higher fasting insulin was unrelated to carbohydrate intake, the overall pattern did not support the model. Moreover, the hypothalamic hunger pathways were inhibited in relation to the increased fasting insulin, and the energy intake was not increased. The browning pathway in the sWAT was inhibited at higher insulin levels, but the daily energy expenditure was not altered.Conclusions: Two of the predictions were partially supported (and hence also partially not supported) and the other three predictions were not supported. We conclude that the CIM does not explain the impact of dietary macronutrients on adiposity in mice. (C) 2019 The Authors. Published by Elsevier GmbH.