The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism

Nature Communications

Volumn 5, Issue , 2014, Pages

  Frost, Gary ^a   Sleeth, Michelle L ^a   Sahuri Arisoylu, Meliz ^a   Lizarbe, Blanca ^b   Cerdan, Sebastian ^b   Brody, Leigh ^a   Anastasovska, Jelena ^a   Ghourab, Samar ^a   Hankir, Mohammed ^a   Zhang, Shuai ^a   Carling, David ^a   Swann, Jonathan R ^c   Gibson, Glenn ^c   Viardot, Alexander ^a   Morrison, Douglas ^d   Thomas, E Louise ^a   Bell, Jimmy D ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b INSTITUTO DE INVESTIGACIONES BIOMÉDICAS ALBERTO SOLS   (Spain)

^c UNIVERSITY OF READING   (United Kingdom)

^d SCOTTISH UNIVERSITIES ENVIRONMENTAL RESEARCH CENTRE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACETIC ACID; ACETIC ACID C 11; ACETYL COENZYME A CARBOXYLASE; CARBOHYDRATE; GLUTAMIC ACID; NEUROPEPTIDE; NEUROTRANSMITTER; ACETIC ACID DERIVATIVE; CARBON; LACTIC ACID;

ANIMAL EXPERIMENT; ANIMAL TISSUE; APPETITE; ARTICLE; BLOOD BRAIN BARRIER; COLON FLORA; COMPUTER ASSISTED EMISSION TOMOGRAPHY; CONTROLLED STUDY; FOOD INTAKE; HOMEOSTASIS; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; OBESITY; OBSERVATIONAL STUDY; PROTEIN EXPRESSION; RAT; ANIMAL; BRAIN; C57BL MOUSE; CATALYSIS; EATING; HYPOTHALAMUS; METABOLISM; PHYSIOLOGY;

ACETATES; ANIMALS; APPETITE; BRAIN; CARBON ISOTOPES; CATALYSIS; EATING; HOMEOSTASIS; HYPOTHALAMUS; LACTIC ACID; MICE; MICE, INBRED C57BL;

EID: 84899892790     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms4611     Document Type: Article

References (48)

1. Swinburn, B. A. et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet 378, 804-814 (2011).
2. Prentice, A. M. & Jebb, S. A. Obesity in Britain: gluttony or sloth? BMJ 311, 437-439 (1995).
3. Prentice, A. M. & Jebb, S. A. Fast foods, energy density and obesity: a possible mechanistic link. Obes. Rev. 4, 187-194 (2003).
4. Eaton, S. B. The ancestral human diet: what was it and should it be a paradigm for contemporary nutrition? Proc. Nutr. Soc. 65, 1-6 (2006).
5. Sleeth, M. L., Thompson, E. L., Ford, H. E., Zac-Varghese, S. E. & Frost, G. Free fatty acid receptor 2 and nutrient sensing: a proposed role for fibre, fermentable carbohydrates and short-chain fatty acids in appetite regulation. Nutr. Res. Rev. 23, 135-145 (2010).
6. Cani, P. D., Dewever, C. & Delzenne, N. M. Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide- 1 and ghrelin) in rats. Br. J. Nutr. 92, 521-526 (2004).
7. Tolhurst, G. et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364-371 (2012).
8. Bodinham, C. L., Hitchen, K. L., Youngman, P. J., Frost, G. S. & Robertson, M. D. Short-term effects of whole-grain wheat on appetite and food intake in healthy adults: a pilot study. Br. J. Nutr. 106, 327-330 (2011).
9. Anastasovska, J. et al. Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment. Obesity 20, 1016-1023 (2012).
10. Parkinson, J. R. et al. Differential patterns of neuronal activation in the brainstem and hypothalamus following peripheral injection of GLP-1, oxyntomodulin and lithium chloride in mice detected by manganese-enhanced magnetic resonance imaging (MEMRI). Neuro Image 44, 1022-1031 (2009).
11. Pouteau, E., Nguyen, P., Ballevre, O. & Krempf, M. Production rates and metabolism of short-chain fatty acids in the colon and whole body using stable isotopes. Proc. Nutr. Soc. 62, 87-93 (2003).
12. Nagashima, H. et al. High-resolution nuclear magnetic resonance spectroscopic study of metabolites in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy. Eur. Spine J. 19, 1363-1368 (2010).
13. Wyss, M. T., Magistretti, P. J., Buck, A. & Weber, B. Labeled acetate as a marker of astrocytic metabolism. J. Cereb. Blood Flow Metab. 31, 1668-1674 (2011).
14. Ge, H. et al. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology 149, 4519-4526 (2008).
15. Kenny, G. D. et al. Novel multifunctional nanoparticle mediates siRNA tumour delivery, visualisation and therapeutic tumour reduction in vivo. J. Control. Release 149, 111-116 (2011).
16. Lin, Y. J. & Koretsky, A. P. Manganese ion enhances T1-weighted MRI during brain activation: an approach to direct imaging of brain function. Magn. Reson. Med. 38, 378-388 (1997).
17. Shen, L. et al. Dietary resistant starch increases hypothalamic POMC expression in rats. Obesity (Silver Spring) 17, 40-45 (2009).
18. Claret, M. et al. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J. Clin. Invest. 117, 2325-2336 (2007).
19. Hu, Z., Cha, S. H., Chohnan, S. & Lane, M. D. Hypothalamic malonyl-CoA as a mediator of feeding behavior. Proc. Natl Acad. Sci. USA 100, 12624-12629 (2003).
20. Violante, I. R. et al. Cerebral activation by fasting induces lactate accumulation in the hypothalamus. Magn. Reson. Med. 62, 279-283 (2009).
21. Delgado, T. C., Violante, I. R., Nieto-Charques, L. & Cerdan, S. Neuroglial metabolic compartmentation underlying leptin deficiency in the obese ob/ob mice as detected by magnetic resonance imaging and spectroscopy methods. J. Cereb. Blood Flow Metab. 31, 2257-2266 (2011).
22. Cerdan, S., Kunnecke, B. & Seelig, J. Cerebral metabolism of [1,2-13C2]acetate as detected by in vivo and in vitro 13C NMR. J. Biol. Chem. 265, 12916-12926 (1990).
23. Lei, H., Poitry-Yamate, C., Preitner, F., Thorens, B. & Gruetter, R. Neurochemical profile of the mouse hypothalamus using in vivo 1H MRS at 14.1T. NMR Biomed. 23, 578-583 (2010).
24. So, P. W. et al. Impact of resistant starch on body fat patterning and central appetite regulation. PLoS ONE 2, e1309 (2007).
25. Pawlak, D. B., Kushner, J. A. & Ludwig, D. S. Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animals. Lancet 364, 778-785 (2004).
26. Darzi, J., Frost, G. S. & Robertson, M. D. Do SCFA have a role in appetite regulation? Proc. Nutr. Soc. 70, 119-128 (2011).
27. Parkinson, J. R., Chaudhri, O. B. & Bell, J. D. Imaging appetite-regulating pathways in the central nervous system using manganese-enhanced magnetic resonance imaging. Neuroendocrinology 89, 121-130 (2009).
28. Deelchand, D. K., Shestov, A. A., Koski, D. M., Ugurbil, K. & Henry, P. G. Acetate transport and utilization in the rat brain. J. Neurochem. 109(Suppl 1): 46-54 (2009).
29. Waniewski, R. A. & Martin, D. L. Preferential utilization of acetate by astrocytes is attributable to transport. J. Neurosci. 18, 5225-5233 (1998).
30. Jiang, L. et al. Increased brain uptake and oxidation of acetate in heavy drinkers. J. Clin. Invest. 123, 1605-1614 (2013).
31. Hankir, M. K., Parkinson, J. R., Bloom, S. R. & Bell, J. D. The effects of glutamate receptor agonists and antagonists on mouse hypothalamic and hippocampal neuronal activity shown through manganese enhanced MRI. Neuro Image 59, 968-978 (2012).
32. Woo, D. H. et al. TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. Cell 151, 25-40 (2012).
33. Dicken, M. S., Tooker, R. E. & Hentges, S. T. Regulation of GABA and glutamate release from proopiomelanocortin neuron terminals in intact hypothalamic networks. J. Neurosci. 32, 4042-4048 (2012).
34. Robertson, M. D., Bickerton, A. S., Dennis, A. L., Vidal, H. & Frayn, K. N. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am. J. Clin. Nutr. 82, 559-567 (2005).
35. Richardson, H. Volatile substance abuse: evaluation and treatment. Hum. Toxicol. 8, 319-322 (1989).
36. O'Shea, D. et al. NEuropeptide Y induced feeding in the rat is mediated by a novel receptor. Endocrinology 138, 196-202 (1997).
37. Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Academic Press, 2007).
38. Oliver, M. et al. MAGfect: a novel liposome formulation for MRI labelling and visualization of cells. Org. Biomol. Chem. 4, 3489-3497 (2006).
39. Bhalerao, S. S. & Raje Harshal, A. Preparation, optimization, characterization, and stability studies of salicylic acid liposomes. Drug Dev. Ind. Pharm. 29, 451-467 (2003).
40. Chatham, J. C. & Forder, J. R. Lactic acid and protein interactions: implications for the NMR visibility of lactate in biological systems. Biochim. Biophys. Acta 1426, 177-184 (1999).
41. Hulsey, M. G., Lu, H., Wang, T., Martin, R. J. & Baile, C. A. Intracerebroventricular (i.c.v.) administration of mouse leptin in rats: behavioral specificity and effects on meal patterns. Physiol. Behav. 65, 445-455 (1998).
42. Fray, P. J., Sahakian, B. J., Robbins, T. W., Koob, G. F. & Iversen, S. D. An observational method for quantifying the behavioural effects of dopamine agonists: contrasting effects of d-amphetamine and apomorphine. Psychopharmacology (Berl) 69, 253-259 (1980).
43. Adrian, T. E. et al. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 89, 1070-1077 (1985).
44. Kreymann, B. et al. Isolation and characterisation of GLP-1 7-36 amide from rat intestine. Elevated levels in diabetic rats. FEBS Lett. 242, 167-170 (1988).
45. Bewick, G. A. et al. Mice with hyperghrelinemia are hyperphagic and glucose intolerant and have reduced leptin sensitivity. Diabetes 58, 840-846 (2009).
46. Chaudhri, O. B. et al. Differential hypothalamic neuronal activation following peripheral injection of GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance imaging. Biochem. Biophys. Res. Commun. 350, 298-306 (2006).
47. Cerdan, S., Parrilla, R., Santoro, J. & Rico, M. 1H NMR detection of cerebral myo-inositol. FEBS Lett. 187, 167-172 (1985).
48. Provencher, S. W. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn. Reson. Med. 30, 672-679 (1993).