Silvia Barja-Fernandez1,2,3, José María Moreno-Navarrete3,4, Cintia Folgueira1,3,5, Gemma Xifra3,4, Mònica Sabater3,4, Cecilia Castelao1,3, Johan FernØ6, Rosaura Leis2,3, Carlos Diéguez3,5, Felipe F Casanueva3,7, Wifredo Ricart3,4, Luisa M Seoane1,3, José Manuel Fernandez-Real3,4, Rubén Nogueiras3,5. 1. Grupo Fisiopatología Endocrina, IDIS, Complejo Hospitalario Universitario de Santiago de Compostela, Spain. 2. Departamento de Pediatría, Universidad de Santiago de Compostela, Spain. 3. CIBER Fisiopatología Obesidad y Nutrición, Instituto Salud Carlos III, Spain. 4. Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona Hospital Dr. Josep Trueta, Girona, Spain. 5. Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain. 6. KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. 7. Departamento de Medicina, Universidad de Santiago de Compostela, Spain.
Abstract
SCOPE: Angiopoietin-like protein 4 (ANGPTL-4) regulates plasma lipoprotein levels, but its relevance in human obesity and type 2 diabetes (T2D) is largely unknown. We aim to investigate the regulation of circulating ANGPTL-4 levels in obesity, T2D, and after changes in body weight. METHODS AND RESULTS: Circulating ANGPTL-4 levels were measured in two different cohorts. First, in a cross-sectional study, we evaluated ANGPTL-4 levels in lean and obese patients with normoglycemia or with altered glucose tolerance (AGT; n = 282). Second, in a longitudinal intervention study, 51 obese participants were evaluated. A hypocaloric diet was prescribed, with follow-up 2 years later. ANGPTL-4 levels were significantly increased in obese patients with AGT compared to lean participants. Moreover, ANGPTL-4 was positively correlated with BMI, waist circumference, fat mass, HbA1c, HOMA-IR, fasting triglycerides, and with inflammatory markers. Participants gaining weight after the follow-up showed increased ANGPTL-4 levels in parallel to increased BMI, fat mass, and fasting glucose, while ANGPTL-4 levels were reduced in participants losing weight. CONCLUSION: Our data support a relevant role of ANGPTL-4 in human obesity and its involvement in long-term body weight changes.
SCOPE: Angiopoietin-like protein 4 (ANGPTL-4) regulates plasma lipoprotein levels, but its relevance in humanobesity and type 2 diabetes (T2D) is largely unknown. We aim to investigate the regulation of circulating ANGPTL-4 levels in obesity, T2D, and after changes in body weight. METHODS AND RESULTS: Circulating ANGPTL-4 levels were measured in two different cohorts. First, in a cross-sectional study, we evaluated ANGPTL-4 levels in lean and obesepatients with normoglycemia or with altered glucose tolerance (AGT; n = 282). Second, in a longitudinal intervention study, 51 obeseparticipants were evaluated. A hypocaloric diet was prescribed, with follow-up 2 years later. ANGPTL-4 levels were significantly increased in obesepatients with AGT compared to lean participants. Moreover, ANGPTL-4 was positively correlated with BMI, waist circumference, fat mass, HbA1c, HOMA-IR, fasting triglycerides, and with inflammatory markers. Participants gaining weight after the follow-up showed increased ANGPTL-4 levels in parallel to increased BMI, fat mass, and fasting glucose, while ANGPTL-4 levels were reduced in participants losing weight. CONCLUSION: Our data support a relevant role of ANGPTL-4 in humanobesity and its involvement in long-term body weight changes.