靶向肠道微生物群衍生的丁酸盐通过 cAMP-PKA-GCN5 通路改善晚期妊娠母猪的肝脏糖异生,Food & Function

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靶向肠道微生物群衍生的丁酸盐通过 cAMP-PKA-GCN5 通路改善晚期妊娠母猪的肝脏糖异生
Food & Function ( IF 5.1 ) Pub Date : 2022-03-14 , DOI: 10.1039/d2fo00094f
Longshan Qin ₁ , Weilei Yao ₁ , Tongxin Wang ₁ , Taimin Jin ₁ , Baoyin Guo ₁ , Shu Wen ₁ , Feiruo Huang ₁

Affiliation

肠道菌群产生的短链脂肪酸（SCFAs）通过肠-肝轴影响肝脏葡萄糖代谢。本研究旨在探讨肠道微生物群产生的丁酸盐对妊娠晚期母猪肝脏糖异生的影响。240头妊娠晚期初产母猪在饲喂前使用血糖仪进行血糖检测，按照血糖水平分组如下：0~3.0 mmol·L ^-1（低血糖组，LG组）和3.1~ 5.0 毫摩尔 L ^-1（正常血糖组，NG组）。分析了结肠 SCFA 和微生物群、门静脉和肝脏中的 SCFA，以及肝脏样本中的乙酰化和磷酸化水平。检查来自怀孕母猪的肝细胞中丁酸盐对肝葡萄糖糖异生的影响。体内实验表明，与NG组相比，LG组的生殖性能、血清葡萄糖代谢指数、结肠丁酸和产丁酸菌均降低。相关性分析发现结肠丁酸盐、丁酸盐产生菌与血清葡萄糖代谢指数呈正相关。此外，与NG组相比，LG组肝脏cAMP浓度、PKA活性、GCN5磷酸化、G6P和PEPCK表达降低，PGC1-α乙酰化增加。在体外，丁酸钠显着刺激晚期妊娠母猪肝细胞LG组的cAMP浓度、PKA活性、GCN5磷酸化、G6P和PEPCK的表达，并抑制PGC-1α乙酰化。有趣的是，另一个体内实验表明，日粮 1-酮糖是肠道细菌的天然调节剂，可显着增加孕晚期母猪的丁酸盐和产丁酸盐细菌，并改善繁殖性能和血清葡萄糖代谢指标。总之，我们发现靶向肠道微生物群衍生的丁酸盐可以通过 cAMP-PKA-GCN5 通路改善妊娠晚期母猪的肝脏糖异生。

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Targeting gut microbiota-derived butyrate improves hepatic gluconeogenesis through the cAMP-PKA-GCN5 pathway in late pregnant sows

Short chain fatty acids (SCFAs) produced by gut microbiota affected hepatic glucose metabolism via the gut–liver axis. The present study aimed to investigate the effects of butyrate produced by gut microbiota on hepatic gluconeogenesis in late-pregnancy sows. A total of 240 primiparous sows in late pregnancy were tested for blood glucose using a glucose meter before feeding and grouped according to their blood glucose level as follows: 0–3.0 mmol L⁻¹ (low blood glucose group, LG group) and 3.1–5.0 mmol L⁻¹ (normal blood glucose group, NG group). Colonic SCFAs and microbiota, SCFAs in the portal vein and liver, and acetylation and phosphorylation levels in the liver samples were analyzed. Hepatocytes from pregnant sows were examined for the effect of butyrate on hepatic glucose gluconeogenesis. In vivo experiments showed that the reproductive performance, serum glucose metabolism index, colonic butyrate and butyrate-producing bacteria decreased in the LG group compared with the NG group. Correlation analysis found a positive correlation among colonic butyrate, butyrate-producing bacteria and the serum glucose metabolism index. Moreover, the hepatic cAMP concentration, PKA activity, GCN5 phosphorylation, and the expression of G6P and PEPCK were decreased and PGC1-α acetylation was increased in the LG group compared with the NG group. In vitro, sodium butyrate significantly stimulated the cAMP concentration, PKA activity, GCN5 phosphorylation, and the expression of G6P and PEPCK and inhibited PGC-1α acetylation in the LG group of hepatocytes from late-pregnancy sows. Interestingly, another in vivo experiment showed that dietary 1-kestose, a natural regulator of gut bacteria, significantly increased butyrate and butyrate-producing bacteria, and improved the reproductive performance and serum glucose metabolism index in late-pregnancy sows. Taken together, we found that targeting gut microbiota-derived butyrate could improve hepatic gluconeogenesis through the cAMP-PKA-GCN5 pathway in late-pregnancy sows.

更新日期：2022-03-14

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