1. Testosterone treatment is associated with reduced adipose tissue dysfunction and nonalcoholic fatty liver disease in obese hypogonadal men.
- Author
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Maseroli E, Comeglio P, Corno C, Cellai I, Filippi S, Mello T, Galli A, Rapizzi E, Presenti L, Truglia MC, Lotti F, Facchiano E, Beltrame B, Lucchese M, Saad F, Rastrelli G, Maggi M, and Vignozzi L
- Subjects
- Adult, Biopsy methods, Cross-Sectional Studies, Humans, Insulin Resistance, Italy epidemiology, Male, Middle Aged, Mitochondria drug effects, Mitochondria metabolism, Protective Agents administration & dosage, Protective Agents pharmacokinetics, Treatment Outcome, Hypogonadism diagnosis, Hypogonadism drug therapy, Hypogonadism epidemiology, Intra-Abdominal Fat drug effects, Intra-Abdominal Fat metabolism, Intra-Abdominal Fat pathology, Lipid Metabolism drug effects, Liver drug effects, Liver metabolism, Liver pathology, Non-alcoholic Fatty Liver Disease drug therapy, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Obesity diagnosis, Obesity drug therapy, Obesity metabolism, Testosterone administration & dosage, Testosterone pharmacokinetics
- 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.
- Published
- 2021
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