
Obesity and metabolic dysfunction severely influence prostate cell function: role of insulin and IGF 1
Author(s) -
LLópez Fernando,
SarmentoCabral André,
HerreroAguayo Vicente,
Gahete Manuel D.,
Castaño Justo P.,
Luque Raúl M.
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13109
Subject(s) - endocrinology , medicine , igfbp3 , insulin , glucose homeostasis , prostate cancer , homeostasis , insulin resistance , biology , hormone , obesity , endocrine system , crosstalk , prostate , growth factor , cancer , receptor , physics , optics
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 IGF 1, 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/ IGF 1 regulatory axis are present in PG s, 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 IGF 1 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 IGF 1 axes could play a relevant pathophysiological role.