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Effects of Totum-63 on glucose homeostasis and post-prandial glycemia: a translational study
American Journal of Physiology-Endocrinology and Metabolism ( IF 5.1 ) Pub Date : 2021-05-03 , DOI: 10.1152/ajpendo.00629.2020
Vivien Chavanelle 1 , Yolanda F Otero 1 , Florian Le Joubioux 2 , Doriane Ripoche 1 , Maxime Bargetto 2 , Aurore Vluggens 1 , Christophe Montaurier 3 , Gisèle Pickering 4, 5 , Gilles Ducheix 4, 5 , Claude Dubray 4, 5 , Christian Dualé 4, 5 , Sylvia Boulliau 4, 5 , Nicolas Macian 4, 5 , Geoffroy Marceau 6 , Vincent Sapin 6 , Frédéric Dutheil 7 , Bruno Guigas 8 , Thierry Maugard 9 , Nathalie Boisseau 10 , Murielle Cazaubiel 2 , Sébastien L Peltier 2 , Pascal Sirvent 1
Affiliation  

Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 weeks, and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men (mean age 51.5 years, BMI 27.6 kg.m-2) for 4 weeks. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain while lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63 supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by PCoA analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an OGTT was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5g.day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multi-targeted action on different metabolic organs.

中文翻译:

Totum-63 对葡萄糖稳态和餐后血糖的影响:一项转化研究

2 型糖尿病 (T2D) 的全球患病率正在上升,到 2045 年可能影响 7 亿人。Totum-63 是一种富含多酚的天然成分,旨在降低 T2D 的风险。我们首先在 14 名超重男性(平均年龄51.5岁,BMI 27.6 kg.m -2) 4 周。在喂食 HFD 的小鼠中,Totum-63 减少了体重和脂肪量的增加,而瘦体重没有变化。此外,补充 Totum-63 的小鼠的粪便能量排泄更高,这表明消化道中的卡路里吸收减少。在肠道中,粪便微生物群的宏基因组分析揭示了 HFD 诱导的微生物失衡的部分恢复,如微生物群组成的 PCoA 分析所示。HFD 诱导的 HOMA-IR 评分增加在补充小鼠中被延迟,并且对 OGTT 的胰岛素反应显着降低,这表明 Totum-63 可以预防 HFD 相关的葡萄糖稳态损伤。有趣的是,这些改善可能与皮下脂肪组织和比目鱼肌中恢复的胰岛素信号传导有关。在肝脏中,HFD 诱导的脂肪变性减少了 40%(如甘油三酯含量所示)。在随后的男性研究中,Totum-63 (5g.day-1 ) 改善了对高碳水化合物早餐测试(84% kcal 碳水化合物)的葡萄糖和胰岛素反应。它具有良好的耐受性,没有报告有临床意义的不良事件。总的来说,这些数据表明 Totum-63 可以改善 HFD 喂养的小鼠和超重个体的葡萄糖稳态,可能是通过对不同代谢器官的多靶向作用。
更新日期:2021-05-04
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