title: Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements.
abstract: We recently demonstrated that testosterone dosing ameliorated the metabolic profile and reduced visceral adipose tissue (VAT) in a high-fat diet (HFD)-induced rabbit model of metabolic syndrome (MetS). We studied the effects of HFD and in vivo testosterone dosing on VAT function and the adipogenic capacity of rabbit preadipocytes isolated from VAT of regular diet (RD), HFD, and testosterone-treated HFD rabbits. VAT was studied by immunohistochemistry, western blot, and RT-PCR. Isolated rPADs were exposed to adipocyte differentiating mixture (DIM) to evaluate adipogenic potential. Adipocyte size was significantly increased in HFD VAT compared with RD, indicating adipocyte dysfunction, which was normalized by testosterone dosing. Accordingly, perilipin, an anti-lipolytic protein, was significantly increased in HFD VAT, when compared with other groups. HFD VAT was hypoxic, while testosterone dosing normalized VAT oxygenation. In VAT, androgen receptor expression was positively associated with mRNA expression of GLUT4 (SLC2A4) (insulin-regulated glucose transporter) and STAMP2 (STEAP4) (androgen-dependent gene required for insulin signaling). In testosterone-treated HFD VAT, STAMP2 mRNA was significantly increased when compared with the other groups. Moreover, GLUT4 membrane translocation was significantly reduced in HFD VAT, compared with RD, and increased by testosterone. In DIM-exposed preadipocytes from HFD, triglyceride accumulation, adipocyte-specific genes, insulin-stimulated triglyceride synthesis, glucose uptake, and GLUT4 membrane translocation were reduced compared with preadipocytes from RD and normalized by in vivo testosterone dosing. In conclusion, testosterone dosing in a MetS animal model positively affects VAT functions. This could reflect the ability of testosterone in restoring insulin sensitivity in VAT, thus counteracting metabolic alterations.
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini, 6, Florence 50139, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Maneschi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Morelli
authors.forename: Sandra
authors.initials: S
authors.lastname: Filippi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cellai
authors.forename: Paolo
authors.initials: P
authors.lastname: Comeglio
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzanti
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Calcagno
authors.forename: Erica
authors.initials: E
authors.lastname: Sarchielli
authors.forename: Linda
authors.initials: L
authors.lastname: Vignozzi
authors.forename: Farid
authors.initials: F
authors.lastname: Saad
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.forename: Gabriella B
authors.initials: GB
authors.lastname: Vannelli
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005434:Flow Cytometry; D007150:Immunohistochemistry; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000627:therapeutic use*
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone