title: Obesity- and gender-dependent role of endogenous somatostatin and cortistatin in the regulation of endocrine and metabolic homeostasis in mice.
abstract: Somatostatin (SST) and cortistatin (CORT) regulate numerous endocrine secretions and their absence [knockout (KO)-models] causes important endocrine-metabolic alterations, including pituitary dysregulations. We have demonstrated that the metabolic phenotype of single or combined SST/CORT KO-models is not drastically altered under normal conditions. However, the biological actions of SST/CORT are conditioned by the metabolic-status (e.g. obesity). Therefore, we used male/female SST- and CORT-KO mice fed low-fat (LF) or high-fat (HF) diet to explore the interplay between SST/CORT and obesity in the control of relevant pituitary-axes and whole-body metabolism. Our results showed that the SST/CORT role in the control of GH/prolactin secretions is maintained under LF- and HF-diet conditions as SST-KOs presented higher GH/prolactin-levels, while CORT-KOs displayed higher GH- and lower prolactin-levels than controls under both diets. Moreover, the impact of lack of SST/CORT on the metabolic-function was gender- and diet-dependent. Particularly, SST-KOs were more sensitive to HF-diet, exhibiting altered growth and body-composition (fat/lean percentage) and impaired glucose/insulin-metabolism, especially in males. Conversely, only males CORT-KO under LF-diet conditions exhibited significant alterations, displaying higher glucose-levels and insulin-resistance. Altogether, these data demonstrate a tight interplay between SST/CORT-axis and the metabolic status in the control of endocrine/metabolic functions and unveil a clear dissociation of SST/CORT roles.
authors.affiliation: Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain.|Hospital Universitario Reina Sofía (HURS), Córdoba, Spain.|CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.|Campus de Excelencia Internacional Agroalimentario (ceiA3), Córdoba, Spain.
authors.forename: Raúl M
authors.initials: RM
authors.lastname: Luque
authors.affiliation: Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain.|Hospital Universitario Reina Sofía (HURS), Córdoba, Spain.|CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.|Campus de Excelencia Internacional Agroalimentario (ceiA3), Córdoba, Spain.|Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago and Jesse Brown Veteran Affairs Medical Center, Research and Development Division, Chicago, IL, USA.
authors.forename: José
authors.initials: J
authors.lastname: Cordoba-Chacon
authors.affiliation: Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain.|Hospital Universitario Reina Sofía (HURS), Córdoba, Spain.|CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.|Campus de Excelencia Internacional Agroalimentario (ceiA3), Córdoba, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Pozo-Salas
authors.affiliation: CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.|Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Porteiro
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: de Lecea
authors.affiliation: CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.|Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Nogueiras
authors.affiliation: Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain.|Hospital Universitario Reina Sofía (HURS), Córdoba, Spain.|CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.|Campus de Excelencia Internacional Agroalimentario (ceiA3), Córdoba, Spain.
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Gahete
authors.affiliation: Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain.|Hospital Universitario Reina Sofía (HURS), Córdoba, Spain.|CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.|Campus de Excelencia Internacional Agroalimentario (ceiA3), Córdoba, Spain.
authors.forename: Justo P
authors.initials: JP
authors.lastname: Castaño
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006706:Homeostasis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010902:Pituitary Gland / Q000378:metabolism* / Q000473:pathology; D012727:Sex Characteristics; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D009479:Neuropeptides; C099323:cortistatin; D013004:Somatostatin