Abstract
Context:
Recent studies have shown that xenin can act in the hypothalamus, reducing food intake through a leptin- and melanocortin system-independent mechanism.
Objective:
To evaluate the impact of body mass reduction on the blood and cerebrospinal fluid (CSF) levels of xenin.
Design and setting:
Thirteen obese patients (11 women) selected for roux-in-Y gastric bypass surgery were evaluated before and approximately 8 months after surgery. Xenin was determined in serum and CSF by radioimmunoassay.
Results:
As compared with lean subjects, obese patients have increased blood levels of xenin, which reduce after surgery. There are significant correlations between blood xenin and blood leptin and insulin levels. CSF concentration of xenin is ∼10-fold lower than blood levels, and is significantly higher in obese subjects as compared with lean ones, returning to normal levels after body mass reduction. There is a significant linear correlation between CSF and blood levels of xenin.
Conclusion:
Xenin is present in the human CSF in a concentration ∼10-fold lower than the blood. Both blood and CSF xenin are correlated with blood levels of important markers of adiposity, leptin and insulin. The levels of CSF xenin are linearly correlated with blood xenin, independently of patient body mass, suggesting that either its transport across the blood–brain barrier is not saturated in the concentration range detected in this study or that there is a coordinated release of xenin from the periphery and the CNS.
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References
Feurle GE, Hamscher G, Kusiek R, Meyer HE, Metzger JW . Identification of xenin, a xenopsin-related peptide, in the human gastric mucosa and its effect on exocrine pancreatic secretion. J Biol Chem 1992; 267: 22305–22309.
Hamscher G, Meyer HE, Metzger JW, Feurle GE . Distribution, formation, and molecular forms of the peptide xenin in various mammals. Peptides 1995; 16: 791–797.
Alexiou C, Zimmermann JP, Schick RR, Schusdziarra V . Xenin—a novel suppressor of food intake in rats. Brain Res 1998; 800: 294–299.
Cline MA, Nandar W, Rogers JO . Xenin reduces feed intake by activating the ventromedial hypothalamus and influences gastrointestinal transit rate in chicks. Behav. Brain Res 2007; 179: 28–32.
Leckstrom A, Kim ER, Wong D, Mizuno TM . Xenin a gastrointestinal peptide, regulates feeding independent of the melanocortin signaling pathway. Diabetes 2009; 58: 87–94.
Cooke JH, Patterson M, Patel SR, Smith KL, Ghatei MA, Bloom SR et al. Peripheral and central administration of xenin and neurotensin suppress food intake in rodents. Obesity (Silver Spring) 2009; 17: 1135–1143.
Velloso LA, Schwartz MW . Altered hypothalamic function in diet-induced obesity. Int J Obes 2011; 35: 1455–1465.
Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 282: 1568–1575.
Hukshorn CJ, Saris WH, Westerterp-Plantenga MS, Farid AR, Smith FJ, Campfield LA . Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J Clin Endocrinol Metab 2000; 85: 4003–4009.
Banks WA, DiPalma CR, Farrell CL . Impaired transport of leptin across the blood-brain barrier in obesity. Peptides 1999; 20: 1341–1345.
Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996; 348: 159–161.
El-Haschimi K, Pierroz DD, Hileman SM, Bjørbaek C, Flier JS . Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest 2000; 105: 1827–1832.
Gastrointestinal surgery for severe obesity. National Institutes of Health Consensus Development Conference Statement. Am J Clin Nutr 1992; 55(2 Suppl): 615S–619S.
de Carvalho CP, Marin DM, de Souza AL, Pareja JC, Chaim EA, de Barros Mazon S et al. GLP-1 and adiponectin: effect of weight loss after dietary restriction and gastric bypass in morbidly obese patients with normal and abnormal glucose metabolism. Obes Surg 2009; 19: 313–320.
Field BCT, Chaudhri OB, Bloom SR . Bowels control brain: gut hormones and obesity. Nat Rev Endocrinol 2010; 6: 444–453.
Woods SC, D’Alessio DA . Central control of body weight and appetite. J Clin Endocrinol Metab 2008; 93(11 Suppl 1): S37–S50.
Neumiller JJ. . Clinical pharmacology of incretin therapies for type 2 diabetes mellitus: implications for treatment. Clin Ther 2011; 33: 528–576.
Coll AP, Farooqi IS, Challis BG, Yeo GSH, O’Rahilly S . Proopiomelanocortin and energy balance: insights from human and murine genetics. J Clin Endocrinol Metab 2004; 89: 2557–2562.
Kim ER, Mizuno TM . Xenin delays gastric emptying rate and activates the brainstem in mice. Neurosci Lett 2010; 481: 59–63.
Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003; 349: 941–948.
Adam TCM, Westerterp-Plantenga MS . Glucagon-like peptide-1 release and satiety after a nutrient challenge in normal-weight and obese subjects. Br J Nutr 2005; 93: 845–851.
le Roux CW, Aylwin SJB, Batterham RL, Borg CM, Coyle F, Prasad V et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg 2006; 243: 108–114.
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Grants for this work were provided by Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo.
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van de Sande-Lee, S., Cardoso, A., Garlipp, C. et al. Cerebrospinal fluid xenin levels during body mass reduction: no evidence for obesity-associated defective transport across the blood–brain barrier. Int J Obes 37, 416–419 (2013). https://doi.org/10.1038/ijo.2012.70
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DOI: https://doi.org/10.1038/ijo.2012.70
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