Associations of Circulating PYY3-36 Concentrations with Metabolic Syndrome in Extremely Obese Subjects.

BACKGROUND The gut hormone peptide YY3-36 (PYY3-36) plays major roles in regulation of appetite and energy metabolism, mediates beneficial effects of bariatric surgery, and may be a potential weight-reducing and glucose-modulating therapy. Obesity may influence the metabolic expression of circulating PYY3-36 and metabolic markers. We studied the relationship of PYY3-36 concentrations with metabolic syndrome (MetSyn) components, lipids, insulin resistance, and inflammatory biomarkers in subjects with extreme obesity. METHODS We measured MetSyn components and PYY3-36, lipids, hormones, homeostasis model assessment (HOMA) index, and inflammatory biomarkers in consecutively referred patients (180 women and 111 men) aged 18-78 years with body mass index (BMI) ≥40 kg/m2. Associations of PYY3-36 to components, insulin resistance, and biomarkers were examined with partial correlations and linear regression. RESULTS PYY3-36 concentrations were not related to MetSyn components, HOMA index, or to inflammatory biomarker or leptin concentrations. PYY3-36 concentrations correlated with systolic blood pressure (r = 0.21; P < 0.0001) after adjustment for age and gender. In linear regression analysis, PYY3-36 concentrations were associated with systolic blood pressure after adjustment for age, gender, and central obesity in the entire sample (Beta 0.21; 95% CI 0.09-0.34) as well as in subjects not taking blood pressure-lowering medication (Beta 0.19; 95% CI 0.04-0.36). These associations were not statistically significant in the small subset of participants (22%) with type 2 diabetes. CONCLUSIONS In extremely obese patients, fasting PYY3-36 concentrations were linked to systolic blood pressure, but not to other components of MetSyn, suggesting divergence between pathways of blood pressure and glucose/body weight regulation. However, this finding will need to be further investigated.

[1]  K. Bibbins-Domingo,et al.  Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease. , 2015, Archives of medical research.

[2]  P. Kruzliak,et al.  Role of Peptide YY in blood vessel function and atherosclerosis in a rabbit model , 2015, Clinical and experimental pharmacology & physiology.

[3]  R. Wong,et al.  Prevalence of the metabolic syndrome in the United States, 2003-2012. , 2015, JAMA.

[4]  F. Tinahones,et al.  GLP‐1 and peptide YY secretory response after fat load is impaired by insulin resistance, impaired fasting glucose and type 2 diabetes in morbidly obese subjects , 2014, Clinical endocrinology.

[5]  W. Gulliver,et al.  The Association of Serum Total Peptide YY (PYY) with Obesity and Body Fat Measures in the CODING Study , 2014, PloS one.

[6]  R. Batterham,et al.  The role of gut hormone peptide YY in energy and glucose homeostasis: twelve years on. , 2014, Annual review of physiology.

[7]  S. Bloom,et al.  Protein PYY and its role in metabolism. , 2014, Frontiers of hormone research.

[8]  R. Batterham,et al.  Peripheral activation of the Y2-receptor promotes secretion of GLP-1 and improves glucose tolerance. , 2013, Molecular metabolism.

[9]  R. Sturm,et al.  Morbid obesity rates continue to rise rapidly in the United States , 2013, International Journal of Obesity.

[10]  S. Bloom,et al.  The regulation of food intake by the gut-brain axis: implications for obesity , 2013, International Journal of Obesity.

[11]  F. Tinahones,et al.  Particular characteristics of the metabolic syndrome in patients with morbid obesity. , 2013, Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion.

[12]  R. Vigneri,et al.  Very severely obese patients have a high prevalence of type 2 diabetes mellitus and cardiovascular disease , 2013, Acta Diabetologica.

[13]  S. Bloom,et al.  Translational studies on PYY as a novel target in obesity. , 2011, Current opinion in pharmacology.

[14]  H. Huikuri,et al.  High serum fasting peptide YY (3–36) is associated with obesity-associated insulin resistance and type 2 diabetes , 2011, Regulatory Peptides.

[15]  J. Després,et al.  Treatment of lipid disorders in obesity , 2011, Expert review of cardiovascular therapy.

[16]  S. Msika,et al.  Traditional Anthropometric Parameters Still Predict Metabolic Disorders in Women With Severe Obesity , 2010, Obesity.

[17]  C. Nievergelt,et al.  Peptide YY (PYY) gene polymorphisms in the 3'-untranslated and proximal promoter regions regulate cellular gene expression and PYY secretion and metabolic syndrome traits in vivo. , 2009, The Journal of clinical endocrinology and metabolism.

[18]  G. Di Salvo,et al.  Y2 receptor gene variants reduce the risk of hypertension in obese children and adolescents , 2008, Journal of hypertension.

[19]  J. Rehfeld,et al.  Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome. , 2007, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[20]  L. Heilbronn,et al.  Low serum PYY is linked to insulin resistance in first-degree relatives of subjects with type 2 diabetes , 2006, Neuropeptides.

[21]  J. Levy,et al.  Use and abuse of HOMA modeling. , 2004, Diabetes care.

[22]  Mohammad A Ghatei,et al.  Inhibition of food intake in obese subjects by peptide YY3-36. , 2003, The New England journal of medicine.

[23]  T. Adrian,et al.  Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man. , 1986, The Journal of clinical endocrinology and metabolism.