title: Obesity and metabolic dysfunction severely influence prostate cell function: role of insulin and IGF1.
abstract: Obesity is a major health problem that courses with severe comorbidities and a drastic impairment of homeostasis and function of several organs, including the prostate gland (PG). The endocrine-metabolic regulatory axis comprising growth hormone (GH), insulin and IGF1, which is drastically altered under extreme metabolic conditions such as obesity, also plays relevant roles in the development, modulation and homeostasis of the PG. However, its implication in the pathophysiological interplay between obesity and prostate function is still to be elucidated. To explore this association, we used a high fat-diet obese mouse model, as well as in vitro primary cultures of normal-mouse PG cells and human prostate cancer cell lines. This approach revealed that most of the components of the GH/insulin/IGF1 regulatory axis are present in PGs, where their expression pattern is altered under obesity conditions and after an acute insulin treatment (e.g. Igfbp3), which might have some pathophysiological implications. Moreover, our results demonstrate, for the first time, that the PG becomes severely insulin resistant under diet-induced obesity in mice. Finally, use of in vitro approaches served to confirm and expand the conception that insulin and IGF1 play a direct, relevant role in the control of normal and pathological PG cell function. Altogether, these results uncover a fine, germane crosstalk between the endocrine-metabolic status and the development and homeostasis of the PG, wherein key components of the GH, insulin and IGF1 axes could play a relevant pathophysiological role.
authors.affiliation: Maimónides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofía University Hospital, Cordoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Cordoba, Spain.|International Campus of Excellence on Agrifood, CeiA3, Cordoba, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: L-López
authors.affiliation: Maimónides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofía University Hospital, Cordoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Cordoba, Spain.|International Campus of Excellence on Agrifood, CeiA3, Cordoba, Spain.
authors.forename: André
authors.initials: A
authors.lastname: Sarmento-Cabral
authors.affiliation: Maimónides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofía University Hospital, Cordoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Cordoba, Spain.|International Campus of Excellence on Agrifood, CeiA3, Cordoba, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Herrero-Aguayo
authors.affiliation: Maimónides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofía University Hospital, Cordoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Cordoba, Spain.|International Campus of Excellence on Agrifood, CeiA3, Cordoba, Spain.
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Gahete
authors.affiliation: Maimónides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofía University Hospital, Cordoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Cordoba, Spain.|International Campus of Excellence on Agrifood, CeiA3, Cordoba, Spain.
authors.forename: Justo P
authors.initials: JP
authors.lastname: Castaño
authors.affiliation: Maimónides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofía University Hospital, Cordoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Cordoba, Spain.|International Campus of Excellence on Agrifood, CeiA3, Cordoba, Spain.
authors.forename: Raúl M
authors.initials: RM
authors.lastname: Luque
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D059305:Diet, High-Fat; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
keywords: IGF1; insulin; obesity; prostate; prostate cancer