title: Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice.
abstract: Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity.
authors.affiliation: 1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029, Madrid, Spain [3] Obesity &Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain.
authors.forename: Natalia R
authors.initials: NR
authors.lastname: Moreno
authors.affiliation: Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Balaguer
authors.affiliation: 1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029, Madrid, Spain [3] Obesity &Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: Leire
authors.initials: L
authors.lastname: Méndez-Giménez
authors.affiliation: 1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029, Madrid, Spain [3] Obesity &Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Becerril
authors.affiliation: 1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029, Madrid, Spain [3] Obesity &Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Catalán
authors.affiliation: 1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029, Madrid, Spain [3] Obesity &Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez-Ambrosi
authors.affiliation: Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology University of Bari Medical School, Policlinico Hospital, Bari, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Portincasa
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calamita
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Graça
authors.initials: G
authors.lastname: Soveral
authors.affiliation: 1] Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029, Madrid, Spain.
authors.forename: María M
authors.initials: MM
authors.lastname: Malagón
authors.affiliation: 1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] Department of Endocrinology &Nutrition, Clínica Universidad de Navarra, Pamplona, Spain [3] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029, Madrid, Spain [4] Obesity &Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D051397:Aquaglyceroporins / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051397:Aquaglyceroporins; D020738:Leptin