Frost Gary, Sleeth Michelle L, Sahuri-Arisoylu Meliz, Lizarbe Blanca, Cerdan Sebastian, Brody Leigh, Anastasovska Jelena, Ghourab Samar, Hankir Mohammed, Zhang Shuai, Carling David, Swann Jonathan R, Gibson Glenn, Viardot Alexander, Morrison Douglas, Louise Thomas E, Bell Jimmy D
Faculty of Medicine, Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
Nat Commun. 2014 Apr 29;5:3611. doi: 10.1038/ncomms4611.
Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo(11)C-acetate and PET-CT scanning to show that colonic acetate crosses the blood-brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through (13)C high-resolution magic-angle-spinning that (13)C acetate from fermentation of (13)C-labelled carbohydrate in the colon increases hypothalamic (13)C acetate above baseline levels. Hypothalamic (13)C acetate regionally increases the (13)C labelling of the glutamate-glutamine and GABA neuroglial cycles, with hypothalamic (13)C lactate reaching higher levels than the 'remaining brain'. These observations suggest that acetate has a direct role in central appetite regulation.
据报道，饮食中可被微生物群在结肠中发酵的碳水化合物摄入量增加会降低体重，但其机制尚不清楚。在这里，我们使用体内¹¹C-醋酸盐和PET-CT扫描来表明结肠中的醋酸盐穿过血脑屏障并被大脑摄取。腹腔注射醋酸盐会导致食欲抑制和下丘脑神经元激活模式。我们还表明，给予醋酸盐与乙酰辅酶A羧化酶的激活以及有利于食欲抑制的调节性神经肽表达谱的变化有关。此外，我们通过¹³C高分辨率魔角旋转证明，结肠中¹³C标记的碳水化合物发酵产生的¹³C醋酸盐会使下丘脑¹³C醋酸盐高于基线水平。下丘脑¹³C醋酸盐局部增加了谷氨酸-谷氨酰胺和GABA神经胶质循环的¹³C标记，下丘脑¹³C乳酸盐水平高于“其余大脑”。这些观察结果表明，醋酸盐在中枢食欲调节中具有直接作用。
