Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation.
Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation.
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DOI：
10.3389/fnut.2021.675267
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发表时间：
2021
影响因子：
5
通讯作者：
Roopchand DE
中科院分区：
文献类型：
--
作者：
Mezhibovsky E;Knowles KA;He Q;Sui K;Tveter KM;Duran RM;Roopchand DE
低纤维但高脂肪和糖的西方饮食（WD）会导致肥胖和非酒精性脂肪肝（NAFLD）。补充富含B型原花青素（PAC）的葡萄多酚（GP）可以减轻心脏代谢疾病的症状，并改变肠道微生物群及其代谢产物。我们假设GP介导的代谢改善与微生物代谢物如短链脂肪酸（SCFAs）的改变相关。为了更接近地模拟WD，C57 BL/6 J雄性小鼠被喂食高蔗糖和乳脂的低纤维饮食以及20%蔗糖水（代表含糖饮料）沿着。该WD补充有1%GP（WD-GP）以研究GP对能量平衡、SCFA谱和肠道代谢的影响。与WD喂养的小鼠相比，WD-GP组具有较高的瘦体重沿着较低的脂肪量、体重和肝脂肪变性，尽管从蔗糖水中消耗更多的热量。间接和直接量热法显示，补充GP的小鼠的肥胖减少可能是由于它们的能量消耗更大，这导致与WD喂养的小鼠相比能量效率更低。补充GP的小鼠具有更高丰度的嗜粘蛋白阿克曼氏菌（Akkermansia muciniphila），这是一种据报道增加能量消耗的肠道微生物。结肠内容物中的短链脂肪酸测量结果显示，补充GP的小鼠具有较低浓度的丁酸盐（远端肠的主要能量底物）和减少的戊酸盐（腐败SCFA）。GP补充还导致乙酸盐：丙酸盐比率降低，表明肝脏脂肪生成减少。考虑到补充GP的小鼠中较高的蔗糖消耗和降低的丁酸水平，我们假设肠上皮细胞将代谢葡萄糖和果糖作为替代能源。回肠葡萄糖转运蛋白-2（GLUT 2，SLC 2A 2）的mRNA水平增加，表明葡萄糖和果糖摄取增加。回肠组织中己酮糖激酶（KHK）的表达增加，表明果糖分解增加。GP诱导的肠道碳水化合物氧化增加由以下因素支持：（1）十二指肠丙酮酸脱氢酶（PDH）基因表达增加，（2）空肠和结肠组织中乳酸脱氢酶a（LDHa）：LDHb比值降低，以及（3）十二指肠和结肠乳酸浓度降低。这些数据表明，GP通过减少由于肠道利用增加而产生脂肪的丁酸盐和糖的门静脉递送来防止WD诱导的肥胖和肝脂肪变性。
A Western Diet (WD) low in fiber but high in fats and sugars contributes to obesity and non-alcoholic fatty liver disease (NAFLD). Supplementation with grape polyphenols (GPs) rich in B-type proanthocyanidins (PACs) can attenuate symptoms of cardiometabolic disease and alter the gut microbiota and its metabolites. We hypothesized that GP-mediated metabolic improvements would correlate with altered microbial metabolites such as short chain fatty acids (SCFAs). To more closely mimic a WD, C57BL/6J male mice were fed a low-fiber diet high in sucrose and butterfat along with 20% sucrose water to represent sugary beverages. This WD was supplemented with 1% GPs (WD-GP) to investigate the impact of GPs on energy balance, SCFA profile, and intestinal metabolism. Compared to WD-fed mice, the WD-GP group had higher lean mass along with lower fat mass, body weight, and hepatic steatosis despite consuming more calories from sucrose water. Indirect and direct calorimetry revealed that reduced adiposity in GP-supplemented mice was likely due to their greater energy expenditure, which resulted in lower energy efficiency compared to WD-fed mice. GP-supplemented mice had higher abundance of Akkermansia muciniphila, a gut microbe reported to increase energy expenditure. Short chain fatty acid measurements in colon content revealed that GP-supplemented mice had lower concentrations of butyrate, a major energy substrate of the distal intestine, and reduced valerate, a putrefactive SCFA. GP-supplementation also resulted in a lower acetate:propionate ratio suggesting reduced hepatic lipogenesis. Considering the higher sucrose consumption and reduced butyrate levels in GP-supplemented mice, we hypothesized that enterocytes would metabolize glucose and fructose as a replacement energy source. Ileal mRNA levels of glucose transporter-2 (GLUT2, SLC2A2) were increased indicating higher glucose and fructose uptake. Expression of ketohexokinase (KHK) was increased in ileum tissue suggesting increased fructolysis. A GP-induced increase in intestinal carbohydrate oxidation was supported by: (1) increased gene expression of duodenal pyruvate dehydrogenase (PDH), (2) a decreased ratio of lactate dehydrogenase a (LDHa): LDHb in jejunum and colon tissues, and (3) decreased duodenal and colonic lactate concentrations. These data indicate that GPs protect against WD-induced obesity and hepatic steatosis by diminishing portal delivery of lipogenic butyrate and sugars due to their increased intestinal utilization.
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影响因子：
29
作者：
Jang C;Hui S;Lu W;Cowan AJ;Morscher RJ;Lee G;Liu W;Tesz GJ;Birnbaum MJ;Rabinowitz JD
通讯作者：
Rabinowitz JD
影响因子：
7.7
作者：
Butler AA;Kozak LP
通讯作者：
Kozak LP
影响因子：
24.5
作者：
Anhe, Fernando F.;Nachbar, Renato T.;Marette, Andre
通讯作者：
Marette, Andre
影响因子：
6.1
作者：
Casanova-Marti, Angela;Serrano, Joan;Pinent, Montserrat
通讯作者：
Pinent, Montserrat
影响因子：
5.8
作者：
Ejtahed, Hanieh-Sadat;Tito, Raul Y.;Larijani, Bagher
通讯作者：
Larijani, Bagher