E Maseroli1, P Comeglio1, C Corno1, I Cellai1, S Filippi2, T Mello3, A Galli3, E Rapizzi4, L Presenti5, M C Truglia5, F Lotti1, E Facchiano5, B Beltrame5, M Lucchese5, F Saad6, G Rastrelli1, M Maggi4,7, L Vignozzi8,9. 1. Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, 50134, Florence, Italy. 2. Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, University of Florence, Viale Pieraccini 6, 50134, Florence, Italy. 3. Gastroenterology Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, 50134, Florence, Italy. 4. Endocrinology Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, 50134, Florence, Italy. 5. General, Bariatric and Metabolic Surgery Unit, Santa Maria Nuova Hospital, , Piazza Santa Maria Nuova, 1, 50122, Florence, Italy. 6. Medical Affairs, Bayer AG, Kaiser-Wilhelm-Allee 1, 51373, Leverkusen, Germany. 7. I.N.B.B. (Istituto Nazionale Biostrutture E Biosistemi), Viale delle Medaglie d'Oro 305, 00136, Rome, Italy. 8. Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, 50134, Florence, Italy. linda.vignozzi@unifi.it. 9. I.N.B.B. (Istituto Nazionale Biostrutture E Biosistemi), Viale delle Medaglie d'Oro 305, 00136, Rome, Italy. linda.vignozzi@unifi.it.
Abstract
PURPOSE: In both preclinical and clinical settings, testosterone treatment (TTh) of hypogonadism has shown beneficial effects on insulin sensitivity and visceral and liver fat accumulation. This prospective, observational study was aimed at assessing the change in markers of fat and liver functioning in obese men scheduled for bariatric surgery. METHODS: Hypogonadal patients with consistent symptoms (n = 15) undergoing 27.63 ± 3.64 weeks of TTh were compared to untreated eugonadal (n = 17) or asymptomatic hypogonadal (n = 46) men. A cross-sectional analysis among the different groups was also performed, especially for data derived from liver and fat biopsies. Preadipocytes isolated from adipose tissue biopsies were used to evaluate insulin sensitivity, adipogenic potential and mitochondrial function. NAFLD was evaluated by triglyceride assay and by calculating NAFLD activity score in liver biopsies. RESULTS: In TTh-hypogonadal men, histopathological NAFLD activity and steatosis scores, as well as liver triglyceride content were lower than in untreated-hypogonadal men and comparable to eugonadal ones. TTh was also associated with a favorable hepatic expression of lipid handling-related genes. In visceral adipose tissue and preadipocytes, TTh was associated with an increased expression of lipid catabolism and mitochondrial bio-functionality markers. Preadipocytes from TTh men also exhibited a healthier morpho-functional phenotype of mitochondria and higher insulin-sensitivity compared to untreated-hypogonadal ones. CONCLUSIONS: The present data suggest that TTh in severely obese, hypogonadal individuals induces metabolically healthier preadipocytes, improving insulin sensitivity, mitochondrial functioning and lipid handling. A potentially protective role for testosterone on the progression of NAFLD, improving hepatic steatosis and reducing intrahepatic triglyceride content, was also envisaged. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02248467, September 25th 2014.
PURPOSE: In both preclinical and clinical settings, testosterone treatment (TTh) of hypogonadism has shown beneficial effects on insulin sensitivity and visceral and liver fat accumulation. This prospective, observational study was aimed at assessing the change in markers of fat and liver functioning in obesemen scheduled for bariatric surgery. METHODS: Hypogonadal patients with consistent symptoms (n = 15) undergoing 27.63 ± 3.64 weeks of TTh were compared to untreated eugonadal (n = 17) or asymptomatic hypogonadal (n = 46) men. A cross-sectional analysis among the different groups was also performed, especially for data derived from liver and fat biopsies. Preadipocytes isolated from adipose tissue biopsies were used to evaluate insulin sensitivity, adipogenic potential and mitochondrial function. NAFLD was evaluated by triglyceride assay and by calculating NAFLD activity score in liver biopsies. RESULTS: In TTh-hypogonadal men, histopathological NAFLD activity and steatosis scores, as well as liver triglyceride content were lower than in untreated-hypogonadal men and comparable to eugonadal ones. TTh was also associated with a favorable hepatic expression of lipid handling-related genes. In visceral adipose tissue and preadipocytes, TTh was associated with an increased expression of lipid catabolism and mitochondrial bio-functionality markers. Preadipocytes from TThmen also exhibited a healthier morpho-functional phenotype of mitochondria and higher insulin-sensitivity compared to untreated-hypogonadal ones. CONCLUSIONS: The present data suggest that TTh in severely obese, hypogonadal individuals induces metabolically healthier preadipocytes, improving insulin sensitivity, mitochondrial functioning and lipid handling. A potentially protective role for testosterone on the progression of NAFLD, improving hepatic steatosis and reducing intrahepatic triglyceride content, was also envisaged. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02248467, September 25th 2014.
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