Grape Polyphenols May Prevent High-Fat Diet-Induced Dampening of the Hypothalamic-Pituitary-Adrenal Axis in Male Mice.
Grape Polyphenols May Prevent High-Fat Diet-Induced Dampening of the Hypothalamic-Pituitary-Adrenal Axis in Male Mice.
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DOI：
10.1210/jendso/bvad095
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发表时间：
2023-08-01
影响因子：
4.1
通讯作者：
Roopchand, Diana E.
中科院分区：
文献类型：
--
作者：
Mezhibovsky, Esther;Tveter, Kevin M.;Villa-Rodriguez, Jose A.;Bacalia, Karen;Kshatriya, Dushyant;Desai, Nikhil;Cabales, Alrick;Wu, Yue;Sui, Ke;Duran, Rocio M.;Bello, Nicholas T.;Roopchand, Diana E.
关键词：
慢性高脂饮食（HFD）消耗导致与胆汁酸（BA）保留相关的肥胖，胆汁酸（BA）抑制重要的调节轴，如下丘脑-垂体-肾上腺轴（HPAA）。HFD由于HPAA的抑制和皮质酮（CORT）的产生和外周代谢的减少而损害营养感测和能量平衡。我们评估了富含原花青素的葡萄多酚（GP）提取物是否可以预防HFD诱导的能量失衡和HPAA失调。雄性C57 BL 6/J小鼠喂食HFD或补充有0.5%w/w GP的HFD（HFD-GP）17周。 GP补充减少体重增加和肝脏脂肪，同时增加能量消耗和HPAA调节激素、CORT、瘦素和PYY的昼夜节律。GP诱导的改善伴随着回肠或肝组织中IL 6、IL 1b和Tnfa的mRNA水平降低以及厚壁菌门（包括已知的BA代谢菌）盲肠丰度降低。补充GP的小鼠具有较低浓度的循环BA，包括疏水性和HPAA抑制BA，但盲肠水平较高的牛磺酸结合的BA拮抗法尼醇X受体（FXR）。与HFD喂养的小鼠相比，补充GP的小鼠肝脏Cyp 7a 1和Cyp 27 a1的mRNA水平增加，表明FXR活化减少，BA合成增加。补充GP的小鼠还具有降低的肝脏Abcc 3和回肠Ibabp和Ostβ，表明较少的BA转移到肠细胞和循环中。相对于HFD喂养的小鼠，CORT和BA代谢酶（Akr 1d 1和Srd 5a 1）增加，而Hsd 11b 1在GP补充小鼠中减少。GP可通过改善HPAA的激素控制并诱导具有较少细胞毒性和HPAA抑制但具有较大FXR拮抗作用的BA特征来减弱HFD诱导的体重增加。
Chronic high-fat diet (HFD) consumption causes obesity associated with retention of bile acids (BAs) that suppress important regulatory axes, such as the hypothalamic–pituitary–adrenal axis (HPAA). HFD impairs nutrient sensing and energy balance due to a dampening of the HPAA and reduced production and peripheral metabolism of corticosterone (CORT). We assessed whether proanthocyanidin-rich grape polyphenol (GP) extract can prevent HFD-induced energy imbalance and HPAA dysregulation. Male C57BL6/J mice were fed HFD or HFD supplemented with 0.5% w/w GPs (HFD-GP) for 17 weeks. GP supplementation reduced body weight gain and liver fat while increasing circadian rhythms of energy expenditure and HPAA-regulating hormones, CORT, leptin, and PYY. GP-induced improvements were accompanied by reduced mRNA levels of Il6, Il1b, and Tnfa in ileal or hepatic tissues and lower cecal abundance of Firmicutes, including known BA metabolizers. GP-supplemented mice had lower concentrations of circulating BAs, including hydrophobic and HPAA-inhibiting BAs, but higher cecal levels of taurine-conjugated BAs antagonistic to farnesoid X receptor (FXR). Compared with HFD-fed mice, GP-supplemented mice had increased mRNA levels of hepatic Cyp7a1 and Cyp27a1, suggesting reduced FXR activation and more BA synthesis. GP-supplemented mice also had reduced hepatic Abcc3 and ileal Ibabp and Ostβ, indicative of less BA transfer into enterocytes and circulation. Relative to HFD-fed mice, CORT and BA metabolizing enzymes (Akr1d1 and Srd5a1) were increased, and Hsd11b1 was decreased in GP supplemented mice. GPs may attenuate HFD-induced weight gain by improving hormonal control of the HPAA and inducing a BA profile with less cytotoxicity and HPAA inhibition, but greater FXR antagonism.
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影响因子：
5.6
作者：
Garcia M;Thirouard L;Sedès L;Monrose M;Holota H;Caira F;Volle DH;Beaudoin C
通讯作者：
Beaudoin C
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
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：
5.9
作者：
FAITH, DP
通讯作者：
FAITH, DP
DOI：
10.1073/pnas.1219451110
发表时间：
2013-05-28
影响因子：
11.1
作者：
Everard, Amandine;Belzer, Clara;Cani, Patrice D.
通讯作者：
Cani, Patrice D.