Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus
Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims...
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China Science Publishing & Media Ltd.
2024-06-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024092 |
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| author | Liu Chang Yu Hao Xia Hongyi Wang Ziwei Li Bolin Xue Hongmei Jin Sheng Xiao Lin Wu Yuming Guo Qi |
| author_facet | Liu Chang Yu Hao Xia Hongyi Wang Ziwei Li Bolin Xue Hongmei Jin Sheng Xiao Lin Wu Yuming Guo Qi |
| author_sort | Liu Chang |
| collection | DOAJ |
| description | Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats <sc>(220‒250 g)</sc> are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, <sc>10 g/L</sc> in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow. Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%; P<0.05), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%; P<0.05) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1 and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin. In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB. |
| format | Article |
| id | doaj-art-4b242814950e450d8330babf8bfd5142 |
| institution | Kabale University |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | China Science Publishing & Media Ltd. |
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| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-4b242814950e450d8330babf8bfd51422025-01-17T05:58:26ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-06-01561823183210.3724/abbs.202409220d259ccButyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleusLiu Chang0Yu Hao1Xia Hongyi2Wang Ziwei3Li Bolin4Xue Hongmei5Jin Sheng6Xiao Lin7Wu Yuming8Guo Qi9["Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Reproduction, the Second Hospital of Hebei Medical University, Shijiazhuang 050017, China"]["Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China","Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang 050017, China","The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China","Hebei Key Laboratory of Cardiovascular Homeostasis and Aging, Shijiazhuang 050017, China"]["Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China","Experimental Center for Teaching, Hebei Medical University, Shijiazhuang 050017, China","Hebei Key Laboratory of Cardiovascular Homeostasis and Aging, Shijiazhuang 050017, China"]Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats <sc>(220‒250 g)</sc> are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, <sc>10 g/L</sc> in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow. Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%; P<0.05), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%; P<0.05) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1 and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin. In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB.https://www.sciengine.com/doi/10.3724/abbs.2024092heart failureparaventricular nucleussympathetic nerve activitymicrogliainflammation |
| spellingShingle | Liu Chang Yu Hao Xia Hongyi Wang Ziwei Li Bolin Xue Hongmei Jin Sheng Xiao Lin Wu Yuming Guo Qi Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus Acta Biochimica et Biophysica Sinica heart failure paraventricular nucleus sympathetic nerve activity microglia inflammation |
| title | Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus |
| title_full | Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus |
| title_fullStr | Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus |
| title_full_unstemmed | Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus |
| title_short | Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus |
| title_sort | butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus |
| topic | heart failure paraventricular nucleus sympathetic nerve activity microglia inflammation |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024092 |
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