Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, Gansu 730000, People's Republic of China.
Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, Gansu 730000, People's Republic of China.
Sci Total Environ. 2024 Sep 15;943:173835. doi: 10.1016/j.scitotenv.2024.173835. Epub 2024 Jun 6.
Chronic exposure to cold temperature is known to elevate blood pressure, leading to a condition known as cold-induced hypertension (CIH). Our previous research suggested correlations between alterations in gut microbiota, decrease in butyrate level, and the onset and progression of CIH. However, the role of butyrate in CIH and the underlying mechanisms need further investigation.
We exposed Specific Pathogen Free (SPF) rats to continuous cold temperature (4 ± 1 °C) for 6 weeks to establish a CIH rat model. Rats were divided into different groups by dose and duration, and the rats under cold were administered with butyrate (0.5 or 1 g/kg/day) daily. We assessed hypertension-associated phenotypes, pathological morphological changes, and endocrine-related phenotypes of brown adipose tissue (BAT). The effects of butyrate on gut microbiota and intestinal content metabolism were evaluated by 16s RNA sequencing and non-targeted metabolomics, respectively.
The systolic blood pressure (SBP) of rats exposed to cold after supplemented with butyrate were significantly lower than that of the Cold group. Butyrate may increase the species, abundance, and diversity of gut microbiota in rats. Specifically, butyrate intervention enriched beneficial bacterial genera, such as Lactobacillaceae, and decreased the levels of harmful bacteria genera, such as Actinobacteriota and Erysipeiotrichaceae. Cold exposure significantly increased BAT cells and the number of mitochondria. After butyrate supplementation, the levels of peroxisome proliferator-activated receptor gamma coactivator 1a and fibroblast growth factor 21 in BAT were significantly elevated (P < 0.05), and the volume and number of lipid droplets increased. The levels of ANG II and high-density lipoprotein were elevated in the Cold group but decreased after butyrate supplementation.
Butyrate may attenuate blood pressure in CIH by promoting the growth of beneficial bacteria and the secretion of beneficial derived factors produced by BAT, thus alleviating the elevation of blood pressure induced by cold. This study demonstrates the anti-hypertensive effects of butyrate and its potential therapeutic mechanisms, offering novel insights to the prevention and treatment of CIH in populations living or working in cold environments.
已知慢性暴露于寒冷温度会导致血压升高，从而引发冷诱导高血压（CIH）。我们之前的研究表明，肠道微生物群的改变、丁酸盐水平降低与 CIH 的发生和进展之间存在相关性。然而，丁酸盐在 CIH 中的作用及其潜在机制仍需进一步研究。
我们将 SPF 大鼠暴露于持续的寒冷温度（4±1°C）下 6 周，以建立 CIH 大鼠模型。大鼠按剂量和时间长短分为不同组，寒冷组大鼠每天给予丁酸盐（0.5 或 1g/kg/天）。我们评估了与高血压相关的表型、棕色脂肪组织（BAT）的病理形态变化和与内分泌相关的表型。通过 16s RNA 测序和非靶向代谢组学分别评估丁酸盐对肠道微生物群和肠道内容物代谢的影响。
补充丁酸盐后，暴露于寒冷环境的大鼠的收缩压（SBP）明显低于寒冷组。丁酸盐可能会增加大鼠肠道微生物群的种类、丰度和多样性。具体来说，丁酸盐干预增加了有益细菌属，如乳杆菌科的丰度，降低了有害细菌属，如放线菌门和红螺菌科的水平。寒冷暴露显著增加了 BAT 细胞和线粒体的数量。补充丁酸盐后，BAT 中过氧化物酶体增殖物激活受体γ共激活因子 1a 和成纤维细胞生长因子 21 的水平显著升高（P<0.05），并且脂质滴的体积和数量增加。ANG II 和高密度脂蛋白的水平在寒冷组中升高，但在补充丁酸盐后降低。
丁酸盐通过促进有益细菌的生长和 BAT 分泌有益的衍生因子，可能减轻寒冷引起的血压升高，从而减轻 CIH 中的血压升高。本研究表明了丁酸盐的降压作用及其潜在的治疗机制，为生活或工作在寒冷环境中的人群预防和治疗 CIH 提供了新的思路。
