title: Tadalafil reduces visceral adipose tissue accumulation by promoting preadipocytes differentiation towards a metabolically healthy phenotype: Studies in rabbits.
abstract: Development of metabolically healthy adipocytes within dysfunctional adipose tissue may represent an attractive way to counteract metabolic syndrome (MetS). In an experimental animal model of high fat diet (HFD)-induced MetS, in vivo, long- and short-term tadalafil treatments were able to reduce visceral adipose tissue (VAT) accumulation and hypertriglyceridemia, and to induce the expression in VAT of the brown fat-specific marker, uncoupling protein 1 (UCP1). VAT preadipocytes (PAD), isolated from the tadalafil-treated HFD rabbits, showed: i) a multilocular morphology; ii) an increased expression of brown fat-specific genes (such as UCP1 and CIDEA); iii) improved mitochondrial structure and dynamic and reduced superoxide production; iv) improved insulin sensitivity. Similar effects were obtained after in vitro tadalafil treatment in HFD rPAD. In conclusion, tadalafil counteracted HFD-associated VAT alterations, by restoring insulin-sensitivity and prompting preadipocytes differentiation towards a metabolically healthy phenotype.
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Maneschi
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Florence, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cellai
authors.affiliation: Department of Experimental Medicine, Medical Pathophysiology, Food Science and Endocrinology Section, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Aversa
authors.affiliation: Gastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mello
authors.affiliation: Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Neuroscience, Drug Research and Child Care, Viale Pieraccini 6, 50139 University of Florence, Florence, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Filippi
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Comeglio
authors.affiliation: Department of Experimental and Clinical Medicine, Largo Brambilla 3, 50134, University of Florence, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bani
authors.affiliation: Department of Experimental and Clinical Medicine, Largo Brambilla 3, 50134, University of Florence, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Guasti
authors.affiliation: Department of Experimental and Clinical Medicine, Largo Brambilla 3, 50134, University of Florence, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Sarchielli
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Salvatore
authors.affiliation: Department of Experimental and Clinical Medicine, Largo Brambilla 3, 50134, University of Florence, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Morelli
authors.affiliation: Department of Experimental and Clinical Medicine, Largo Brambilla 3, 50134, University of Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzanti
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Corcetto
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Corno
authors.affiliation: Department of Experimental Medicine, Medical Pathophysiology, Food Science and Endocrinology Section, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Francomano
authors.affiliation: Gastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Galli
authors.affiliation: Department of Experimental and Clinical Medicine, Largo Brambilla 3, 50134, University of Florence, Italy.
authors.forename: Gabriella Barbara
authors.initials: GB
authors.lastname: Vannelli
authors.affiliation: Department of Experimental Medicine, Medical Pathophysiology, Food Science and Endocrinology Section, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: Diabetes Section Geriatric Unit, Department of Critical Care, Careggi Hospital, Largo Brambilla 3, 50134, Florence, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Florence, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, Viale Morgagni 50, 50134, University of Florence, Florence, Italy. Electronic address: linda.vignozzi@unifi.it.
authors.forename: Linda
authors.initials: L
authors.lastname: Vignozzi
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D011817:Rabbits; D000068581:Tadalafil / Q000008:administration & dosage* / Q000494:pharmacology; D000071256:Uncoupling Protein 1 / Q000378:metabolism
chemical_list: D000071256:Uncoupling Protein 1; D000068581:Tadalafil
keywords: Insulin-resistance; Metabolic syndrome; PDE5; Tadalafil