Guanylin and uroguanylin stimulate lipolysis in human visceral adipocytes.
Uroguanylin and guanylin are secreted by intestinal epithelial cells as prohormones postprandially and act on the hypothalamus to induce satiety. The impact of obesity and obesity-associated type 2 diabetes (T2D) on proguanylin and prouroguanylin expression/secretion as well as the potential role of guanylin and uroguanylin in the control of lipolysis in humans was evaluated.



Circulating and gastrointestinal expression of proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 134 subjects. In addition, plasma proguanylin and prouroguanylin were measured before and after weight loss achieved either by Roux-en-Y gastric bypass (RYGB) (n=24) or after a conventional diet (n=15). The effect of guanylin and uroguanylin (1-100 nmol l(-1)) on lipolysis was determined in vitro in omental adipocytes.



Circulating concentrations of prouroguanylin, but not proguanylin, were decreased in obesity in relation to adiposity. Weight loss achieved by RYGB increased plasma proguanylin and prouroguanylin. Obese T2D individuals showed higher expression of intestinal GUCA2A as well as of the receptors of the guanylin system, GUCY2C and GUCY2D, in omental adipocytes. The incubation with guanylin and uroguanylin significantly stimulated lipolysis in differentiated omental adipocytes, as evidenced by hormone-sensitive lipase phosphorylation at Ser563, an increase in fatty acids and glycerol release together with an upregulation of several lipolysis-related genes, including AQP3, AQP7, FATP1 or CD36.



Both guanylin and uroguanylin trigger lipolysis in human visceral adipocytes. Given the lipolytic action of the guanylin system on visceral adipocytes, the herein reported decrease of circulating prouroguanylin concentrations in obese patients may have a role in excessive fat accumulation in obesity.
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
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Rodríguez
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
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Gómez-Ambrosi
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
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Catalán
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
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Ezquerro
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
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Méndez-Giménez
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
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Becerril
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.|Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
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Ibáñez
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.|Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
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Vila
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.|Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
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Margall
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.|Department of Anesthesia, Clínica Universidad de Navarra, Pamplona, Spain.
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Moncada
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.|Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
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Valentí
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.|Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
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Silva
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
J
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Salvador
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.|Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
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Frühbeck
D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D002352:Carrier Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D004038:Diet, Reducing; D005260:Female; D015390:Gastric Bypass; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000473:pathology*; D008066:Lipolysis; D045265:Natriuretic Peptides / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D012527:Satiation; D015398:Signal Transduction; D002787:Sterol Esterase / Q000378:metabolism; D015431:Weight Loss
D002352:Carrier Proteins; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; C072685:guanylin; C084362:uroguanylin; D002787:Sterol Esterase