Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Nutrients. 2022 Oct 14;14(20):4306. doi: 10.3390/nu14204306.
The role of short-chain fatty acids (SCFAs) in the brain on the developmental programming of hypertension is poorly understood. The present study explored dysregulated tissue levels of SCFAs and expression of SCFA-sensing receptors in the hypothalamic paraventricular nucleus (PVN), a key forebrain region engaged in neural regulation of blood pressure of offspring to maternal high fructose diet (HFD) exposure. We further investigated the engagement of SCFA-sensing receptors in PVN in the beneficial effects of -biotics (prebiotic, probiotic, synbiotic, and postbiotic) on programmed hypertension. Maternal HFD during gestation and lactation significantly reduced circulating butyrate, along with decreased tissue level of butyrate and increased expression of SCFA-sensing receptors, GPR41 and olfr78, and tissue oxidative stress and neuroinflammation in PVN of HFD offspring that were rectified by oral supplement with -biotics. Gene silencing of or mRNA in PVN also protected adult HFD offspring from programmed hypertension and alleviated the induced oxidative stress and inflammation in PVN. In addition, oral supplement with postbiotic butyrate restored tissue butyrate levels, rectified expressions of GPR41 and olfr78 in PVN, and protected against programmed hypertension in adult HFD offspring. These data suggest that alterations in tissue butyrate level, expression of GPR41 and olfr78, and activation of SCFA-sensing receptor-dependent tissue oxidative stress and neuroinflammation in PVN could be novel mechanisms that underlie hypertension programmed by maternal HFD exposure in adult offspring. Furthermore, oral -biotics supplementation may exert beneficial effects on hypertension of developmental origin by targeting dysfunctional SCFA-sensing receptors in PVN to exert antioxidant and anti-inflammatory actions in the brain.
短链脂肪酸（SCFAs）在大脑中对高血压发育编程的作用知之甚少。本研究探讨了下丘脑室旁核（PVN）中 SCFA 感应受体的失调组织水平和表达，PVN 是参与调节后代血压的关键前脑区域，该区域受到母体高果糖饮食（HFD）暴露的影响。我们进一步研究了 SCFA 感应受体在 PVN 中的参与情况，以及益生菌（益生元、益生菌、合生菌和后生元）对程序化高血压的有益作用。妊娠和哺乳期的母体 HFD 显著降低了循环中的丁酸盐水平，同时降低了组织中的丁酸盐水平，增加了 SCFA 感应受体 GPR41 和 olfr78 的表达，以及组织氧化应激和神经炎症在 HFD 后代的 PVN 中，这些都可以通过口服补充益生菌来纠正。PVN 中的 或 mRNA 基因沉默也保护了成年 HFD 后代免受程序化高血压的影响，并减轻了诱导的 PVN 氧化应激和炎症。此外，口服后生元丁酸盐可恢复组织丁酸盐水平，纠正 PVN 中 GPR41 和 olfr78 的表达，并预防成年 HFD 后代的程序化高血压。这些数据表明，组织丁酸盐水平、GPR41 和 olfr78 的表达以及 PVN 中 SCFA 感应受体依赖性组织氧化应激和神经炎症的激活可能是母体 HFD 暴露导致成年后代高血压的新机制。此外，口服益生菌补充剂可能通过靶向 PVN 中功能失调的 SCFA 感应受体发挥抗氧化和抗炎作用，对发育起源的高血压产生有益影响。
