Enterostatin is a pentapeptide[1] derived from a proenzyme in the gastrointestinal tract called procolipase. It reduces food intake, in particular fat intake,[2] when given peripherally or into the brain.[3]
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| IUPAC name
(2S)-2-[[(2S)-1-[2-[[(2S)-1-[(2S)-2-aminopropanoyl]pyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid
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| Other names
Procolipase activation peptide; APGPR; L-Alanyl-L-prolylglycyl-L-prolyl-L-arginine
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3D model (JSmol)
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PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C21H36N8O6 | |
| Molar mass | 496.569 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Chemical structure
editEnterostatin has the sequence Val-Pro-Asp-Pro-Arg in most mammals, but Val-Pro-Gly-Pro-Arg or Val-Pro-Asp-Pro-Arg in rodents and Ala-Pro-Gly-Pro-Arg in humans.[4] The sequence that it necessary for its anorexic effects is X-pro-Y-pro-arg and conserved among several vertebrate species.[5][6]
Function
editEnterostatin has been detected in gut endocrine cells.[7] It is created in the intestine by pancreatic procolipase, the other colipase serving as an obligatory cofactor for pancreatic lipase during fat digestion. Enterostatin can be created in the gastric mucosa and the mucosal epithelia in the small intestine. A high fat diet will cause the procolipase gene transcription and enterostatin to release into the gastrointestinal lumen. Enterostatin appears in the lymph and circulation after a meal. Enterostatin has been shown to selectively reduce fat intake during a normal meal. The testing has been successful with different species.[8]
Signaling pathway
editThe signaling pathway of the peripheral mechanism uses afferent vagal to hypothalamic centers. The central responses are mediated through a pathway including serotonergic and opioidergic components.[9] Enterostatin cuts fat intake, bodyweight, and body fat. This reaction may involve multiple metabolic effects of enterostatin, which include a decrease of insulin secretion,[10] a growth in sympathetic drive to brown adipose tissue, and the stimulation of adrenal corticosteroid secretion. It has been demonstrated that enterostatin stimulates neurons in the amygdala, the arcuate nucleus, the lateral and the ventromedial hypothalamus that have anatomic and functional projections to the paraventricular nucleus (PVN) of the hypothalamus.[11] Additionally, enterostatin regulates the expression of Agouti-related peptide (AgRP) in a complex manner.[12]
A possible pathophysiological role is indicated by studies that have associated low enterostatin output and/or responsiveness to breeds of rat that become obese and prefer dietary fat. Humans with obesity also exhibit a lower secretion from pancreatic procolipase after a test meal, compared with persons of normal weight.[3]
Effects
editIts effects include a reduction of insulin secretion, an increase in sympathetic drive to brown adipose tissue, and the stimulation of adrenal corticosteroid secretion. At the end level, it initiates a sensation of fullness of stomach which could be the reason for its role in regulation of fat intake and reduction of body weight. For enterostatin to be utilized it needs the presence of CCK A receptors. Studies based on rats who lack these receptors have found them to be un-responsive to enterostatin.[13]
When rats have been injected with high doses of enterostatin into the brain the rats ate progressively less food as the dose was increased.[14]: 969 In rats, examination of experiments involving the effects of peripheral or intracerebroventricular administration of enterostatin show this selectively slows down fat consumption.[15]: 8
Medical trials
editAlthough enterostatin-like immunoreactivities exist in blood, brain, and gut, and exogenous enterostatins decrease fat appetite and insulin secretion in rats, the roles of these peptides in human obesity remain to be examined.[16] It has been hypothesized that resistance to enterostatin impairs its effects in obesity.[16]
References
edit- ^ York DA, Teng L, Park-York M (June 2010). "Effects of dietary fat and enterostatin on dopamine and 5-hydroxytrytamine release from rat striatal slices". Brain Res. 1349: 48–55. doi:10.1016/j.brainres.2010.06.036. PMID 20599830. S2CID 7112000.
- ^ Fernstrom, etc; John D. Fernstrom; Ricardo Uauy; Pedro Arroyo (2000). Nutrition and Brain: 5th Nestle Nutrition Workshop, Mexico City. Karger Publishers. p. 76. ISBN 978-3-8055-7166-1.
- ^ a b Erlanson-Albertsson, C; York, D (July 1997). "Enterostatin--a peptide regulating fat intake". Obesity Research. 5 (4). Nature Publishing Group: 360–72. doi:10.1002/j.1550-8528.1997.tb00565.x. ISSN 1930-7381. PMID 9285845.
- ^ Erlanson-Albertsson, C (October 1992). "Enterostatin: the pancreatic procolipase activation peptide--a signal for regulation of fat intake". Nutrition Reviews. 50 (10): 307–10. doi:10.1111/j.1753-4887.1992.tb02473.x. PMID 1436769.
- ^ Lin, L; Okada, S; York, DA; Bray, GA (1994). "Structural requirements for the biological activity of enterostatin". Peptides. 15 (5): 849–54. doi:10.1016/0196-9781(94)90041-8. PMID 7984504.
- ^ Lin, L; York, DA (16 November 2005). "5-HT1B receptors modulate the feeding inhibitory effects of enterostatin". Brain Research. 1062 (1–2): 26–31. doi:10.1016/j.brainres.2005.09.029. PMC 2526559. PMID 16256085.
- ^ Sörhede, M; Erlanson-Albertsson, C; Mei, J; Nevalainen, T; Aho, A; Sundler, F (1996). "Enterostatin in gut endocrine cells--immunocytochemical evidence". Peptides. 17 (4): 609–14. doi:10.1016/0196-9781(96)00017-4. PMID 8804069.
- ^ Jonaidi, H; Rasooli, R (15 January 2013). "Effect of central enterostatin on fat intake in neonatal chicks". Neuroscience Letters. 533: 60–4. doi:10.1016/j.neulet.2012.11.021. PMID 23178475.
- ^ Berger, K; Winzell, MS; Mei, J; Erlanson-Albertsson, C (30 December 2004). "Enterostatin and its target mechanisms during regulation of fat intake". Physiology & Behavior. 83 (4): 623–30. doi:10.1016/j.physbeh.2004.08.040. PMID 15621068.
- ^ Park M, Farrell J, Lemmon K, York DA (October 2009). "Enterostatin alters protein trafficking to inhibit insulin secretion in Beta-TC6 cells". Peptides. 30 (10): 1866–73. doi:10.1016/j.peptides.2009.06.021. PMC 2755607. PMID 19563849.
- ^ Lin, L; York, DA (10 September 2004). "Amygdala enterostatin induces c-Fos expression in regions of hypothalamus that innervate the PVN". Brain Research. 1020 (1–2): 147–53. doi:10.1016/j.brainres.2004.06.029. PMID 15312796.
- ^ Park, M; Oh, H; York, DA (February 2009). "Enterostatin affects cyclic AMP and ERK signaling pathways to regulate Agouti-related protein (AgRP) expression". Peptides. 30 (2): 181–90. doi:10.1016/j.peptides.2008.11.005. PMID 19059445.
- ^ Jean-Pierre Montmayeur; Johannes le Coutre (September 14, 2009). Fat Detection: Taste, Texture, and Post Ingestive Effects. CRC Press; 1 edition. p. 359. ISBN 978-1-4200-6775-0.
- ^ Handbook of biologically active peptides. Londan: Academic Press. 2006. ISBN 978-0-12-369442-3.
- ^ George A. Bray; Donna H. Ryan (2006). Overweight and the Metabolic Syndrome: From Bench to Bedside. Springer; 1 edition. ISBN 978-0-387-32163-9.
- ^ a b Prasad, C; Imamura, M; Debata, C; Svec, F; Sumar, N; Hermon-Taylor, J (March 1999). "Hyperenterostatinemia in premenopausal obese women". The Journal of Clinical Endocrinology and Metabolism. 84 (3): 937–41. doi:10.1210/jcem.84.3.5562. PMID 10084574.