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Diurnal rhythms of plasma GLP-1 levels in normal and overweight/obese subjects: lack of effect of weight loss

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Abstract

Food intake is regulated by not only neurohormonal, but also social, educational, and even cultural factors. Within the former, there is a complex interaction between orexigenic (ghrelin) and anorexigenic (glucagon-like peptide-1 (GLP-1)) factors in order to adjust the food intake to caloric expenditure; however, the number of subjects that are unable to properly balance appetite and body weight is increasing continuously. A loss of circadian or diurnal coordination of any of these factors may be implied in this situation. Special attention has retrieved GLP-1 due to its usefulness as a therapeutic agent against obesity and related alterations. Thus, the objective of the present study was to compare GLP-1 diurnal synthesis between normal weight and overweight/obese subjects, and to evaluate whether weight loss can restore the synthesis rhythms of GLP-1. Three groups of 25 subjects were divided attending to their body mass index (BMI) in normal weight, overweight, or obese subjects. Diurnal (5 points) GLP-1 levels were analyzed. Secondly, an intervention (behavioral-dietary treatment) study was conducted to analyze the effect of weight loss on plasma GLP-1 concentrations. Our results showed that baseline GLP-1 level was significantly lower in normal weight subjects (p = 0.003); furthermore, our cosinor analysis revealed a higher amplitude (p = 0.040) and daily GLP-1 variation (47 %) in these subjects. In fact, our ANOVA data showed a lack of rhythmicity in overweight/obese patients. Weight loss was not able to restore a diurnal rhythm of plasma GLP-1 levels. In summary, the present work shows a disruption of diurnal GLP-1 levels in overweight/obese subjects, which worsen as body fat progresses. The attenuation of the GLP-1 synthesis rhythms may be important to understand the impairment of food intake regulation in overweight/obese subjects.

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Abbreviations

OCDE:

Organisation for Economic Co-operation and Development

CCK:

Cholecystokinin

GLP-1:

Glucagon-like peptide-1

NPY:

Neuropeptide Y

AgRP:

Agouti-related protein

SEEDO:

Spanish Society for the Study of Obesity

MetS:

Metabolic syndrome

References

  1. Adam TC, Jocken J, Westerterp-Plantenga MS (2005) Decreased glucagon-like peptide 1 release after weight loss in overweight/obese subjects. Obes Res 13:710–716

    Article  CAS  PubMed  Google Scholar 

  2. Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med 23:469–480

    Article  CAS  PubMed  Google Scholar 

  3. Ando H, Yanagihara H, Hayashi Y, Obi Y, Tsuruoka S, Takamura T, Kaneko S, Fujimura A (2005) Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology 146:5631–5636

    Article  CAS  PubMed  Google Scholar 

  4. Baillie-Hamilton PF (2002) Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med 8:185–192

    Article  PubMed  Google Scholar 

  5. Bose M, Teixeira J, Olivan B, Bawa B, Arias S, Machineni S, Pi-Sunyer X, Scherer PE, Laferrere B (2010) Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery. J Diabetes 2:47–55

    Article  CAS  PubMed  Google Scholar 

  6. Byberg S, Hansen AL, Christensen DL, Vistisen D, Aadahl M, Linneberg A, Witte DR (2012) Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis. Diabet Med 29:e354–e360

    Article  CAS  PubMed  Google Scholar 

  7. Carr RD, Larsen MO, Jelic K, Lindgren O, Vikman J, Holst JJ, Deacon CF, Ahrén B (2010) Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, nondiabetic men. J Clin Endocrinol Metab 95:872–878

    Article  CAS  PubMed  Google Scholar 

  8. Carter S, Caron A, Richard D, Picard F (2013) Role of leptin resistance in the development of obesity in older patients. Clin Interv Aging 8:829–844

    PubMed Central  CAS  PubMed  Google Scholar 

  9. Duffey KJ, Popkin BM (2011) Energy density, portion size, and eating occasions: contributions to increased energy intake in the United States, 1977–2006. PLoS Med 8:e1001050

    Article  PubMed Central  PubMed  Google Scholar 

  10. Elliot RM, Morgan LM, Tredger JA, Deacon S, Wright J, Marks V (1993) Glucagon-like peptide-1(7–36) amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man—acute postprandial and 24-h secretion patterns. J Endocrinol 138:159–166

    Article  Google Scholar 

  11. Foster GD, Makris AP, Bailer BA (2005) Behavioral treatment of obesity. Am J Clin Nutr 82(1 Suppl):230S–235S

    CAS  PubMed  Google Scholar 

  12. García-Prieto MD, Tébar FJ, Nicolás F, Larqué E, Zamora S, Garaulet M (2007) Cortisol secretary pattern and glucocorticoid feedback sensitivity in women from a Mediterranean area: relationship with anthropometric characteristics, dietary intake and plasma fatty acid profile. Clin Endocrinol (Oxf) 66:185–191

    Article  Google Scholar 

  13. Gargallo Fernández MM, Breton Lesmes I, Basulto Marset J, Quiles Izquierdo J, Formiguera Sala X, Salas-Salvadó J; FESNAD-SEEDO consensus group (2012) Evidence-based nutritional recommendations for the prevention and treatment of overweight and obesity in adults (FESNAD-SEEDO consensus document). The role of diet in obesity treatment (III/III). Nutr Hosp 27:833–864

    Google Scholar 

  14. Hernandez-Morante JJ, Gomez-Santos C, Margareto J, Formiguera X, Martínez CM, González R, Martínez-Augustín O, Madrid JA, Ordovas JM, Garaulet M (2012) Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women. Age (Dordr) 34:1369–1380

    Article  CAS  Google Scholar 

  15. Hernandez-Morante JJ, Gomez-Santos C, Milagro F, Campión J, Martínez JA, Zamora S, Garaulet M (2009) Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue. Int J Obes 33:473–480

    Article  CAS  Google Scholar 

  16. Lionetti L, Mollica MP, Lombardi A, Cavaliere G, Gifuni G, Barletta A (2009) From chronic overnutrition to insulin resistance: the role of fat-storing capacity and inflammation. Nutr Metab Cardiovasc Dis 19:146–152

    Article  CAS  PubMed  Google Scholar 

  17. Cuervo-Zapatel M, Muñoz-Hornillos M, Astiasarán-Anchía I, Martínez-Hernández JA (2004) Alimentación Hospitalaria. Díaz de Santos, Madrid

    Google Scholar 

  18. Mayr S, Erdfelder E, Buchner A, Faul F (2007) A short tutorial of GPower. Tutor Quant Methods Psychol 3:51–59

    Google Scholar 

  19. Meyer-Gerspach AC, Wölnerhanssen B, Beglinger B, Nessenius F, Napitupulu M, Schulte FH, Steinert RE, Beglinger C (2014) Gastric and intestinal satiation in obese and normal weight healthy people. Physiol Behav 129:265–271

    Article  CAS  PubMed  Google Scholar 

  20. Mingrone G, Nolfe G, Gissey GC, Iaconelli A, Leccesi L, Guidone C, Nanni G, Holst JJ (2009) Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion. Diabetologia 52:873–881

    Article  CAS  PubMed  Google Scholar 

  21. Mul JD, Begg DP, Barrera JG, Li B, Matter EK, D’Alessio DA, Woods SC, Seeley RJ, Sandoval DA (2013) High-fat diet changes the temporal profile of GLP-1 receptor-mediated hypophagia in rats. Am J Physiol Regul Integr Comp Physiol 305:R68–R77

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Myers MG Jr, Leibel RL, Seeley RJ, Schwartz MW (2010) Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metab 21:643–651

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. OCDE (Organisation for Economic Co-operation and Development) (2010) In: Obesity and the economics of fat: fit not fat. París, France. http://www.oecd.org/els/health-systems/46068529.pdf. Accessed 23 Sept 2014

  24. Patton DF, Mistlberger RE (2013) Circadian adaptations to meal timing: neuroendocrine mechanisms. Front Neurosci 7:185

    Article  PubMed Central  PubMed  Google Scholar 

  25. Peterli R, Steinert RE, Woelnerhanssen B, Peters T, Christoffel-Courtin C, Gass M, Kern B, von Fluee M, Beglinger C (2012) Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg 22:740–748

    Article  PubMed Central  PubMed  Google Scholar 

  26. Quilliot D, Böhme P, Zannad F, Ziegler O (2008) Sympathetic-leptin relationship in obesity: effect of weight loss. Metabolism 57:555–562

    Article  CAS  PubMed  Google Scholar 

  27. Rocca AS, Brubaker PL (1999) Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology 140:1687–1694

    CAS  PubMed  Google Scholar 

  28. Salas-Salvadó J, Rubio MA, Barbany M, Moreno B (2007) Grupo Colaborativo de la SEEDO 2007 consensus for the evaluation of overweight and obesity and the establishment of therapeutic intervention criteria. Med Clin (Barc) 128:184–196

    Article  Google Scholar 

  29. Sohn JW, Elmquist JK, Williams KW (2013) Neuronal circuits that regulate feeding behavior and metabolism. Trends Neurosci 36:504–512

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J (2011) Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 365:1597–1604

    Article  CAS  PubMed  Google Scholar 

  31. Tchernof A, Després JP (2013) Pathophysiology of human visceral obesity: an update. Physiol Rev 93:359–404

    Article  CAS  PubMed  Google Scholar 

  32. Valassi E, Scacchi M, Cavagnini F (2008) Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis 18:158–168

    Article  CAS  PubMed  Google Scholar 

  33. Varela-Moreiras G, Ruiz E, Valero T, Avila JM, del Pozo S (2013) The Spanish diet: an update. Nutr Hosp 28:13–20

    PubMed  Google Scholar 

  34. Willett WC (1998) Is dietary fat a major determinant of body fat? Am J Clin Nutr 67:556S–562S

    CAS  PubMed  Google Scholar 

  35. Yamaoka-Tojo M, Tojo T, Takahira N, Matsunaga A, Aoyama N, Masuda T, Izumi T (2010) Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease. Cardiovasc Diabetol 9:17

    Article  PubMed Central  PubMed  Google Scholar 

  36. Zhao L (2013) The gut microbiota and obesity: from correlation to causality. Nat Rev Microbiol 11:639–647

    Article  CAS  PubMed  Google Scholar 

  37. Zuther P, Gorbey S, Lemmer B (2009) Chronos-Fit 1.06. http://www.ma.uni-heidelberg.de/inst/phar/lehre/chrono.html. Accessed 23 Sept 2014

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Acknowledgments

We would like to thank the psychologists Magdalena Gomez and Rosario Gomez for their assistance in the psychological and behavioral treatment of overweight and obese patients of the present study. We also want to thank Rubén Cañavate for his assistance in the language editing of the manuscript. The authors have no conflicts of interest to declare. The present work was funded by PMAFI/14/12 project, from the Support for Research Help Program of the Catholic University of Murcia.

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Authors and Affiliations

  1. Department of Nursing. Faculty of Nursing, Catholic University of Murcia, Campus de Guadalupe, s/n, 30107, Murcia, Spain

    Joaquín Santiago Galindo Muñoz, Diana Jiménez Rodríguez & Juan José Hernández Morante

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  1. Joaquín Santiago Galindo Muñoz
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  2. Diana Jiménez Rodríguez
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  3. Juan José Hernández Morante
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Correspondence to Juan José Hernández Morante.

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Muñoz, J.S.G., Rodríguez, D.J. & Morante, J.J.H. Diurnal rhythms of plasma GLP-1 levels in normal and overweight/obese subjects: lack of effect of weight loss. J Physiol Biochem 71, 17–28 (2015). https://doi.org/10.1007/s13105-014-0375-7

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