title: Impact of diet-induced obesity in male mouse reproductive system: The role of advanced glycation end product-receptor for advanced glycation end product axis.
abstract: Obesity represents a route to broad physiological dysfunction affecting major organs including male urogenital system. Hyperglycemia, hyperlipidemia, and oxidative stress associated with obesity augment the formation of reactive metabolic by-products, namely advanced glycation end products (AGEs), leading to increased tissue deposition and damage. The exogenous intake and the endogenous accumulation of AGEs contribute to metabolic and reproductive abnormalities in both women and men. The present study assessed the effects of a diet high in saturated fatty acids (SAFA) on the lipid and metabolic profile (AGE levels, oxidative stress) as well as pathogenic (AGE, receptor for AGEs [RAGE] expression, apoptosis) and morphometric parameters of male reproductive system in vivo. Effects of switching to a diet rich in monounsaturated fatty acids (MUFA) or equal in the proportion MUFA to SAFA were further investigated. SAFA-fed animals were characterized by increased serum lipid concentrations (p < .05) compared to controls, but AGEs and peroxide levels were not significantly different across the different experimental groups. Elevated AGE deposition was detected for the first time in germ cells with a higher staining intensity in animals on the SAFA diet, compared to MUFA or MUFA-SAFA-fed animals or the control samples (p = .018). In Leydig cells, AGE localization was higher in the entire cohort of high-fat-fed animals compared to controls (p < .05). High-fat-fed mice displayed enhanced apoptosis compared to controls (p < .005). Furthermore, prostatic tissue demonstrated reduction in epithelial folding, an effect which was significantly reversed after MUFA diet administration. Our findings provide the basis for further investigation of AGE-RAGE axis in testicular and prostatic disturbances associated with diet-induced obesity. Simple dietetic intervention has beneficial effects on metabolic dysfunction of reproductive system before overt manifestations, indicating glycation as a promising therapeutic target.
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Moschonas
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, Athens 11527, Greece cpiperi@med.uoa.gr.
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.affiliation: 1 Department of Pathology, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.affiliation: 1 Department of Pathology, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Levidou
authors.affiliation: 1 Department of Pathology, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.affiliation: 1 Department of Pathology, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Eleni-Andriana
authors.initials: EA
authors.lastname: Trigka
authors.affiliation: Laboratory for Experimental Surgery and Surgical Research "N.S. Christeas," University of Athens Medical School, Athens 11527, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vlachos
authors.affiliation: Laboratory for Experimental Surgery and Surgical Research "N.S. Christeas," University of Athens Medical School, Athens 11527, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Arapostathi
authors.affiliation: Laboratory for Experimental Surgery and Surgical Research "N.S. Christeas," University of Athens Medical School, Athens 11527, Greece.
authors.forename: Despina
authors.initials: D
authors.lastname: Perrea
authors.affiliation: 1 Department of Urology, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Dionysios
authors.initials: D
authors.lastname: Mitropoulos
authors.affiliation: Endocrine Unit, Third Department of Internal Medicine, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Evanthia
authors.initials: E
authors.lastname: Diamanti-Kandarakis
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
keywords: Advanced glycation end products; apoptosis; obesity; prostate; receptor for advanced glycation end product; testes