title: Antiobesity efficacy of GLP-1 receptor agonist liraglutide is associated with peripheral tissue-specific modulation of lipid metabolic regulators.
abstract: To investigate the role of glucagon-like-peptide-1 receptor (GLP-1R) in peripheral lipid metabolism. Both lean and high-fat diet (HFD)-induced obesity (DIO) rats were used to compare the peripheral effects of the subcutaneous and repeated administration of the GLP-1R agonist liraglutide on the expression of key regulators involved in lipid metabolism, β-oxidation and thermogenesis in liver, abdominal muscle, and epididymal white adipose tissue (eWAT). We observed that liraglutide reduced caloric intake, body weight, and plasma levels of triglycerides and VLDL in a diet-independent manner. However, changes in liver fat content and the expression of lipid metabolism regulators were produced in a diet and tissue-dependent manner. In lean rats, liraglutide increased the gene/protein expression of elements involved in lipogenesis (ChREBP, Acaca/ACC, Fasn/FAS, Scd1/SCD1, PPARα/γ), β-oxidation (CPT1b), and thermogenesis (Cox4i1, Ucp1/UCP1) in eWAT and muscle, which suggest an increase in fatty-acid flux and utilization to activate energy expenditure. Regarding DIO rats, the specific reduction of liver lipid content by liraglutide was associated with a decreased expression of main elements involved in lipogenesis (phospho-ACC), peroxisomal β-oxidation (ACOX1), and lipid flux/storage (Pparγ/PPARγ) in liver, which suggest a recovery of lipid homeostasis. Interestingly, the muscle of DIO rats treated with liraglutide showed a decreased expression of PPARγ and the thermogenic factor UCP1. These results help us to better understand the peripheral mechanisms regulating lipid metabolism that underlay the effectiveness of GLP-1 analogues for the treatment of diabetes and obesity. © 2016 BioFactors, 42(6):600-611, 2016.
authors.affiliation: UGC Salud Mental, Instituto De Investigación Biomédica De Málaga (IBIMA), Universidad De Málaga-Hospital Universitario Regional De Málaga, Avda. Carlos Haya 82, Pabellón De Gobierno, Málaga, Spain.|CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Decara
authors.affiliation: UGC Salud Mental, Instituto De Investigación Biomédica De Málaga (IBIMA), Universidad De Málaga-Hospital Universitario Regional De Málaga, Avda. Carlos Haya 82, Pabellón De Gobierno, Málaga, Spain.|CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Arrabal
authors.affiliation: CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.|Department of Physiology, School of Medicine-CIMUS, University of Santiago De Compostela-Instituto De Investigación Sanitaria, S. Francisco S/N, 15782 Santiago De Compostela, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Beiroa
authors.affiliation: UGC Salud Mental, Instituto De Investigación Biomédica De Málaga (IBIMA), Universidad De Málaga-Hospital Universitario Regional De Málaga, Avda. Carlos Haya 82, Pabellón De Gobierno, Málaga, Spain.|CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rivera
authors.affiliation: UGC Salud Mental, Instituto De Investigación Biomédica De Málaga (IBIMA), Universidad De Málaga-Hospital Universitario Regional De Málaga, Avda. Carlos Haya 82, Pabellón De Gobierno, Málaga, Spain.|CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vargas
authors.affiliation: UGC Salud Mental, Instituto De Investigación Biomédica De Málaga (IBIMA), Universidad De Málaga-Hospital Universitario Regional De Málaga, Avda. Carlos Haya 82, Pabellón De Gobierno, Málaga, Spain.|CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.affiliation: UGC Salud Mental, Instituto De Investigación Biomédica De Málaga (IBIMA), Universidad De Málaga-Hospital Universitario Regional De Málaga, Avda. Carlos Haya 82, Pabellón De Gobierno, Málaga, Spain.|CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Pavón
authors.affiliation: Parque Científico Madrid (PCM), VIVIA Biotech SL, 1 Calle Santiago Grisolia, Suite 205, Tres Cantos, 28760, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Ballesteros
authors.affiliation: CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.|Department of Physiology, School of Medicine-CIMUS, University of Santiago De Compostela-Instituto De Investigación Sanitaria, S. Francisco S/N, 15782 Santiago De Compostela, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Dieguez
authors.affiliation: CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.|Department of Physiology, School of Medicine-CIMUS, University of Santiago De Compostela-Instituto De Investigación Sanitaria, S. Francisco S/N, 15782 Santiago De Compostela, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Nogueiras
authors.affiliation: UGC Salud Mental, Instituto De Investigación Biomédica De Málaga (IBIMA), Universidad De Málaga-Hospital Universitario Regional De Málaga, Avda. Carlos Haya 82, Pabellón De Gobierno, Málaga, Spain.|CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez de Fonseca
authors.affiliation: UGC Salud Mental, Instituto De Investigación Biomédica De Málaga (IBIMA), Universidad De Málaga-Hospital Universitario Regional De Málaga, Avda. Carlos Haya 82, Pabellón De Gobierno, Málaga, Spain.|CIBER OBN, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D003576:Electron Transport Complex IV / Q000378:metabolism; D002149:Energy Intake / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D000069450:Liraglutide / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D053858:Metabolic Networks and Pathways; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D009928:Organ Specificity; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D022722:Thermogenesis / Q000187:drug effects; D000071256:Uncoupling Protein 1 / Q000378:metabolism; D000071246:Uncoupling Protein 2 / Q000378:metabolism; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D019440:Anti-Obesity Agents; D005227:Fatty Acids; D047493:PPAR alpha; D047495:PPAR gamma; C000604373:Ucp1 protein, rat; C000604391:Ucp2 protein, rat; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000069450:Liraglutide; D003576:Electron Transport Complex IV; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: GLP-1; adipose tissue; lipid metabolism; liver; obesity