Leptin Within the Subphysiological to Physiological Range Dose Dependently Improves Male Reproductive Function in an Obesity Mouse Model

• Published in: Endocrinology (Philadelphia) 2016-06, Vol.157 (6), p.2461-2468
• Main Authors: Hoffmann, Annett, Manjowk, Gloria-Maria, Wagner, Isabel Viola, Klöting, Nora, Ebert, Thomas, Jessnitzer, Beate, Lössner, Ulrike, Stukenborg, Jan-Bernd, Blüher, Matthias, Stumvoll, Michael, Söder, Olle, Svechnikov, Konstantin, Fasshauer, Mathias, Kralisch, Susan
• Format: Article
• Language: English
• Subjects: Animals; Body weight; Cytochrome P450; Cytochromes P450; Enzyme-Linked Immunosorbent Assay; Fertility; Follicle Stimulating Hormone - metabolism; Follicle-stimulating hormone; Gene expression; Leptin; Leptin - pharmacology; Leydig Cells - drug effects; Male; Males; Medicin och hälsovetenskap; Mice; Mice, Obese; mRNA; Obesity; Organ Size - drug effects; Physiological effects; Physiology; Real-Time Polymerase Chain Reaction; Seminiferous tubule; Seminiferous Tubules - drug effects; Spermatogenesis; Spermatogenesis - drug effects; Steroid 17-alpha-Hydroxylase - genetics; Steroid 17-alpha-Hydroxylase - metabolism; Testes; Testis - drug effects; Testosterone; Testosterone - metabolism; Tubules
• ISSN: 0013-7227; 1945-7170; 1945-7170
• DOI: 10.1210/en.2015-1966

Obesity has recently been linked with reduced fertility, and the mechanisms underpinning this effect are currently unknown. The adipokine leptin is dysregulated in obesity and affects reproductive tracts; therefore, we investigated the dose-dependent effects of leptin on Leydig cell function and spermatogenesis. Eight-week-old leptin-deficient obese (ob/ob) male mice were treated with subphysiological (0.1- or 0.5-mg/kg body weight [BW]/d) or physiological (3.0-mg/kg BW/d) doses of leptin or saline for 12 weeks (chronic treatment) or 72 hours (acute treatment). We then evaluated male reproductive function markers. Mean testis weight increased significantly in the 0.1- and 3.0-mg/kg BW/d groups compared with saline controls (both P < .05). Intratesticular testosterone levels relative to testis weight significantly increased in the 0.5-mg/kg BW/d group compared with saline controls (P < .05). FSH levels increased in a dose-dependent manner with leptin treatment, whereas LH levels did not change. Leptin treatment significantly up-regulated both mRNA and protein expression of the steroidogenic enzyme cytochrome P450 17A1. Spermatogenesis improved in leptin-treated animals. Significantly more seminiferous tubules were observed in stages I–VIII (P < .01), and there were fewer abnormal seminiferous tubule structures (P < .01). Acute treatment with physiological leptin doses partially improved male reproductive markers without changing BW. Administration of subphysiological to physiological doses of leptin improves Leydig cell function and spermatogenesis.