Tirzepatide suppresses palatable food intake by selectively reducing preference for fat in rodents.
Tirzepatide suppresses palatable food intake by selectively reducing preference for fat in rodents.
复制标题
替泽帕肽通过选择性降低啮齿动物对脂肪的偏好来抑制可口食物的摄入。
DOI：
10.1111/dom.14843
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Hayes,MatthewR
中科院分区：
文献类型：
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作者：
Geisler,CarolineE;Antonellis,MeghanP;Trumbauer,Wolfgang;Martin,JenniferA;Coskun,Tamer;Samms,RicardoJ;Hayes,MatthewR
目的研究葡萄糖依赖性促胰岛素多肽受体（GIPR）激动剂单独或与胰高血糖素样肽-1受体（GLP-1 R）激动剂联合使用对适口性食物摄入的调节作用，以及特定常量营养素在这些偏好中的作用。我们对小鼠和大鼠进行了几种选择的饮食模式的食物和可口的食物选择与单独或双重GIPR和GLP-1 R激动剂。在小鼠中，双重激动剂替瑞帕肽抑制总热量摄入，同时促进食物摄入超过高脂肪/蔗糖饮食。令人惊讶的是，单独的GIPR激动并没有改变食物的选择。在GLP-1 R敲除小鼠中，在野生型小鼠中观察到的替扎帕肽的摄食量变化完全不存在，表明GIPR信号传导不调节食物偏好。在大鼠两种饮食选择模型中，替泽帕肽还选择性抑制可口食物的摄入，但不抑制食物的摄入。这种抑制作用对脂质具有特异性，因为在评估个体适口性大量营养素的选择范例中，GLP-1 R激动剂和双重激动剂处理可显著抑制Crisco（脂质）的摄入，而不减少蔗糖的摄入结论降低对高热量、高脂肪食物的偏好是GLP-1 R和双重GIPR/GLP-1 R激动剂治疗的强大作用，这可能有助于这些药物的减肥成功。
AimTo investigate the role of glucose‐dependent insulinotropic polypeptide receptor (GIPR) agonists alone or combined with glucagon‐like peptide‐1 receptor (GLP‐1R) agonists to regulate palatable food intake and the role of specific macronutrients in these preferences.MethodsTo understand this regulation, we treated mice and rats on several choice diet paradigms of chow and a palatable food option with individual or dual GIPR and GLP‐1R agonists.ResultsIn mice, the dual agonist tirzepatide suppressed total caloric intake, while promoting the intake of chow over a high fat/sucrose diet. Surprisingly, GIPR agonism alone did not alter food choice. The food intake shift observed with tirzepatide in wild‐type mice was completely absent in GLP‐1R knockout mice, suggesting that GIPR signalling does not regulate food preference. Tirzepatide also selectively suppressed the intake of palatable food but not chow in a rat two‐diet choice model. This suppression was specific to lipids, as GLP‐1R agonist and dual agonist treatment in rats on a choice paradigm assessing individual palatable macronutrients robustly inhibited the intake of Crisco (lipid) without decreasing the intake of a sucrose (carbohydrate) solution.ConclusionsDecreasing preference for high‐caloric, high‐fat foods is a powerful action of GLP‐1R and dual GIPR/GLP‐1R agonist therapeutics, which may contribute to the weight loss success of these drugs.