Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
J Endocrinol. 2020 Apr;245(1):155-164. doi: 10.1530/JOE-20-0011.
The known crosstalk between short-chain fatty acids (SCFAs) and the circadian clock is tightly intertwined with feeding time. We aimed to investigate the role of the core clock gene Bmal1 and feeding time in the diurnal rhythms in plasma and caecal SCFA levels and in their effect on the release of the hunger hormone ghrelin in the stomach and colon. WT, Bmal1-/- (ad libitum fed) and night-time-restricted-fed (RF)-Bmal1-/- littermates were killed at zeitgeber time (ZT) 4 and 16. SCFA concentrations were measured by gas chromatography. To investigate the effect of SCFAs on ghrelin release, stomach and colonic full-thickness strips were incubated with Krebs or a SCFA mix mimicking plasma or caecal concentrations, after which octanoyl ghrelin release was measured by RIA. Diurnal rhythms in caecal and plasma SCFAs oscillated in phase but rhythmic changes were abolished in Bmal1-/- mice. RF of Bmal1-/- mice restored fluctuations in caecal SCFAs. Plasma SCFA concentrations failed to affect gastric ghrelin release. The effect of caecal SCFA concentrations on colonic ghrelin release was rhythmic (inhibition at ZT 4, no effect at ZT 16). In Bmal1-/- mice, the inhibitory effect of SCFAs at ZT 4 was abolished. RF Bmal1-/- mice restored the inhibitory effect and increased colonic Clock expression. To conclude, diurnal fluctuations in caecal SCFAs and the effect of SCFAs on colonic ghrelin release are regulated by feeding time, independent of the core clock gene Bmal1. However, local entrainment of other clock genes might contribute to the observed effects.
短链脂肪酸 (SCFA) 与生物钟的已知串扰与进食时间紧密交织。我们旨在研究核心时钟基因 Bmal1 和进食时间在血浆和盲肠 SCFA 水平昼夜节律中的作用，以及它们对胃和结肠饥饿激素 ghrelin 释放的影响。WT、Bmal1-/-（自由进食）和夜间限制喂养 (RF)-Bmal1-/-同窝仔在 Zeitgeber 时间 (ZT) 4 和 16 时被处死。通过气相色谱法测量 SCFA 浓度。为了研究 SCFAs 对 ghrelin 释放的影响，用 Krebs 或模拟血浆或盲肠浓度的 SCFA 混合物孵育胃和结肠全层条带，然后通过 RIA 测量辛酰 ghrelin 释放。盲肠和血浆 SCFA 的昼夜节律波动相位一致，但在 Bmal1-/- 小鼠中节律变化被消除。RF-Bmal1-/- 小鼠恢复了盲肠 SCFA 的波动。血浆 SCFA 浓度未能影响胃 ghrelin 释放。结肠 ghrelin 释放的 caecal SCFA 浓度的影响呈节律性（ZT 4 时抑制，ZT 16 时无影响）。在 Bmal1-/- 小鼠中，SCFAs 在 ZT 4 时的抑制作用被消除。RF-Bmal1-/- 小鼠恢复了抑制作用并增加了结肠 Clock 表达。总之，盲肠 SCFAs 的昼夜波动和 SCFAs 对结肠 ghrelin 释放的影响受进食时间调节，与核心时钟基因 Bmal1 无关。然而，其他时钟基因的局部驯化可能有助于观察到的效果。
