Sleeve Gastrectomy Improves High-Fat Diet-Associated Hepatic Steatosis Independent of the Glucagon-like-Petpide-1 Receptor in Rats.
Sleeve Gastrectomy Improves High-Fat Diet-Associated Hepatic Steatosis Independent of the Glucagon-like-Petpide-1 Receptor in Rats.
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DOI：
10.1007/s11605-022-05361-6
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发表时间：
2022-08
影响因子：
3.2
通讯作者：
Kindel, Tammy L.
中科院分区：
文献类型：
--
作者：
Barron, Matthew;Hayes, Hailey;Fernando, Deemantha G.;Geurts, Aron M.;Kindel, Tammy L.
胃袖状切除术（SG）后胃肠激素胰高血糖素样肽-1（GLP-1）升高。大鼠和临床研究支持SG后GLP-1 R信号传导的作用，而小鼠研究反驳了这一点。因此，我们开发了一种全球GLP-1 R敲除（KO）大鼠，以检验功能性GLP-1 R对诱导SG后体重减轻和代谢疾病改善至关重要的假设。在刘易斯品系背景的GLP-1 R基因外显子2中创建4 bp缺失，以创建全局GLP-1 R KO大鼠。对KO和刘易斯大鼠给予高脂或低脂饲料，进行表型分析，然后进行SG或假手术，并评估GLP-1 R KO对手术和代谢疗效的影响。GLP-1 R的缺失产生了一种肥胖倾向的啮齿动物，而能量消耗没有变化。与刘易斯大鼠相比，尽管葡萄糖浓度相似，但经口灌胃葡萄糖后，通过高脂饮食增强的雄性和雌性KO大鼠的胰岛素浓度均显著更高。与刘易斯大鼠相比，GLP-1 R KO导致肝肿大和甘油三酯沉积增加。当考虑对体重、葡萄糖耐量的疗效和脂肪肝疾病的稳健改善时，我们发现SG GLP-1 R KO组和刘易斯组之间无差异。大鼠中GLP-1 R的缺失导致肥胖、胰岛素抵抗和重度脂肪变性增加。与小鼠研究相似，功能性GLP-1 R对SG在刘易斯大鼠中的代谢疗效并不重要，但重要的是包括脂肪变性，支持SG后脂肪肝疾病改善的GLP-1 R非依赖性机制。
The gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is increased after sleeve gastrectomy (SG). Rat and clinical studies support, while mouse studies refute, a role for GLP-1R signaling after SG. Therefore, we developed a global GLP-1R knockout (KO) rat to test the hypothesis that a functional GLP-1R is critical to induce weight loss and metabolic disease improvement after SG. A 4bp deletion was created in exon 2 of the GLP-1R gene on a Lewis strain background to create a global GLP-1R KO rat. KO and Lewis rats were placed on a high-fat or low-fat diet and phenotyped followed by SG or Sham surgery and assessed for the effect of GLP-1R KO on surgical and metabolic efficacy. Loss of the GLP-1R created an obesity-prone rodent without changes in energy expenditure. Both male and female KO rats had significantly greater insulin concentrations after an oral glucose gavage, augmented by a high-fat diet, compared to Lewis rats despite similar glucose concentrations. GLP-1R KO caused hepatomegaly and increased triglyceride deposition compared to Lewis rats. We found no difference between SG GLP-1R KO and Lewis groups when considering efficacy on body weight, glucose tolerance, and a robustly preserved improvement in fatty liver disease. Loss of the GLP-1R in rats resulted in increased adiposity, insulin resistance, and severe steatosis. A functional GLP-1R is not critical to the metabolic efficacy of SG in Lewis rats, similar to mouse studies, but importantly including steatosis, supporting a GLP-1R independent mechanism for the improvement in fatty liver disease after SG.
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影响因子：
16.6
作者：
Bozadjieva-Kramer N;Shin JH;Shao Y;Gutierrez-Aguilar R;Li Z;Heppner KM;Chiang S;Vargo SG;Granger K;Sandoval DA;MacDougald OA;Seeley RJ
通讯作者：
Seeley RJ
影响因子：
82.9
作者：
Scrocchi, LA;Brown, TJ;Drucker, DJ
通讯作者：
Drucker, DJ
影响因子：
5
作者：
Huang, Jing;Liu, Yunhan;Zhang, Huinan
通讯作者：
Zhang, Huinan
影响因子：
120.7
作者：
Salminen, Paulina;Helmio, Mika;Victorzon, Mikael
通讯作者：
Victorzon, Mikael
影响因子：
4.8
作者：
Garibay, Darline;McGavigan, Anne K.;Cummings, Bethany P.
通讯作者：
Cummings, Bethany P.