Daily transient coating of the intestine leads to weight loss and improved glucose tolerance.
Daily transient coating of the intestine leads to weight loss and improved glucose tolerance.
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DOI：
10.1016/j.metabol.2021.154917
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Tavakkoli A
中科院分区：
文献类型：
--
作者：
Lo T;Lee Y;Tseng CY;Hu Y;Connelly MA;Mantzoros CS;Karp JM;Tavakkoli A
Roux-en-Y胃旁路手术（RYGB）已被证明是肥胖相关2型糖尿病（T2 D）的金标准治疗，但由于其潜在风险和GI解剖结构的永久性变化，许多T2 D患者不符合条件或不愿意进行手术。我们之前已经描述了一种新的口服制剂LuCI，其提供近端肠的瞬时涂层并模拟RYGB的作用。在此，我们的目的是研究长期给予LuCI对体重和葡萄糖稳态的影响。高脂肪饮食的Sprague-Dawley大鼠获得饮食诱导的肥胖（DIO），每天接受5周LuCI或生理盐水作为对照（n = 8/组）。在整个实验过程中监测每日体重和葡萄糖耐量。在5周时，通过手术放置的颈静脉导管，在肠内葡萄糖推注之前和期间采集全身血液，以研究参与葡萄糖代谢的关键激素的变化。为了阐明LuCI对营养吸收的影响，同时测量粪便排出量和食物摄入量，并使用弹式量热法分析均质化粪便样品。在5周时，LuCI动物的体重比对照组低8.3%，并且具有较低的空腹葡萄糖水平（77.6 ± 3.8 mg/dl对99.1 ± 2.7 mg/dl，P<0.001）。LuCI治疗组动物的基线胰岛素和HOMA-IR较低。餐后，LuCI组在葡萄糖激发后GLP-1和GIP分泌增加。血清脂质分析显示低密度脂蛋白水平降低，突出了不仅改善血糖控制而且改变心血管风险的潜力。然后，我们研究了LuCI对近端肠阻断的影响是否可能在能量平衡中发挥作用。弹式量热分析表明LuCI减少了热量吸收，但热量消耗没有差异。我们证明LuCI重现了RYGB后观察到的身体和激素变化，并可以改善DIO大鼠模型中的体重增加和改善胰岛素敏感性。由于LuCI的作用是短暂的，没有全身吸收，LuCI有可能成为超重或肥胖T2 D患者的新疗法。
Roux-en-Y gastric bypass surgery (RYGB) has been shown to be the gold standard treatment for obesity associated type-2-diabetes (T2D), however many T2D patients do not qualify or are reluctant to proceed with surgery due to its potential risks and permanent changes to GI anatomy. We have previously described a novel oral formulation, LuCI, that provides a transient coating of the proximal bowel and mimics the effects of RYGB. Herein, we aim to investigate outcome of chronic LuCI administration on weight and glucose homeostasis. Sprague-Dawley rats on a high fat diet achieving diet-induced obesity (DIO) received 5 weeks of daily LuCI or normal saline as control (n = 8/group). Daily weights and glucose tolerance were monitored throughout the experiment. At 5 weeks, systemic blood was sampled through a surgically placed jugular vein catheter, before and during an intestinal glucose bolus, to investigate changes in key hormones involved in glucose metabolism. To elucidate the effects of LuCI on nutrient absorption, fecal output and food intake were measured simultaneously with the analysis of homogenized stool samples performed using bomb calorimetry. At 5 weeks, LuCI animals weighted 8.3% less and had lower fasting glucose levels than Controls (77.6 ± 3.8 mg/dl vs. 99.1 ± 2.7 mg/dl, P<0.001). LuCI-treated animals had lower baseline insulin and HOMA-IR. Post-prandially, LuCI group had increased GLP-1 and GIP secretion following a glucose challenge. Serum lipid analysis revealed lowered LDL levels highlighting the potential to not only improve glucose control but also modify cardiovascular risk. We then investigated whether LuCI’s effect on proximal bowel exclusion may play a role in energy balance. Bomb calorimetry analysis suggested that LuCI reduced calorie absorption with no difference in caloric consumption. We demonstrated that LuCI recapitulates the physical and hormonal changes seen after RYGB and can ameliorate weight gain and improve insulin sensitivity in a DIO rat model. Since LuCI’s effect is transient and without systemic absorption, LuCI has the potential to be a novel therapy for overweight or obese T2D patients.
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影响因子：
3.9
作者：
Bedi S;Garcia E;Jeyarajah EJ;Shalaurova I;Perez-Matos MC;Jiang ZG;Dullaart RPF;Matyus SP;Kirk WJ;Otvos JD;Davidson WS;Connelly MA
通讯作者：
Connelly MA
DOI：
10.1056/nejmsa2032271
发表时间：
2021-06-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fang M;Wang D;Coresh J;Selvin E
通讯作者：
Selvin E
影响因子：
4.9
作者：
Cummings, D. E.
通讯作者：
Cummings, D. E.
影响因子：
39.2
作者：
COLDITZ, GA;WILLETT, WC;MANSON, JE
通讯作者：
MANSON, JE
影响因子：
16.9
作者：
Courcoulas AP;Belle SH;Neiberg RH;Pierson SK;Eagleton JK;Kalarchian MA;DeLany JP;Lang W;Jakicic JM
通讯作者：
Jakicic JM