期刊
NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms4611
关键词
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资金
- Medical Research Council (MRC) UK
- Biotechnology and Biological Sciences Research Council (BBSRC) UK
- National Institute for Health Research (NIHR) UK
- Integrative Mammalian Biology (IMB) Capacity Building Award
- NIHR Imperial Biomedical Research Centre Funding Scheme
- EurOCHIP [FP7-HEALTH-2009-241592]
- NIHR senior investigator award
- NHMRC overseas-based clinical research fellowship [535976]
- [FP7-People-2009-256365]
- [SAF2011-23622]
- [S/BMD 23492010]
- [IPT-2012-1331-060000]
- [BES-2009-027615]
- BBSRC [BB/H004815/1, BB/H004971/1] Funding Source: UKRI
- MRC [MC_U120027537, MC_U120061305] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/H004815/1, BB/H004971/1] Funding Source: researchfish
- Medical Research Council [MC_U120061305, MC_U120027537] Funding Source: researchfish
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 C-11-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 C-13 high-resolution magic-angle-spinning that C-13 acetate from fermentation of C-13-labelled carbohydrate in the colon increases hypothalamic C-13 acetate above baseline levels. Hypothalamic C-13 acetate regionally increases the C-13 labelling of the glutamate-glutamine and GABA neuroglial cycles, with hypothalamic C-13 lactate reaching higher levels than the 'remaining brain'. These observations suggest that acetate has a direct role in central appetite regulation.
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