PO-01-077 The effects of testosterone treatment on fat tissue dysfunction and nonalcoholic fatty liver disease in obese men undergoing bariatric surgery

Abstract

Substitution treatment of hypogonadism in clinical and experimental models has shown beneficial effects on insulin sensitivity and accumulation of visceral and liver fat. Aim of the study was to analyze the effects of testosterone replacement therapy on benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) clinical parameters, adipose tissue dysfunction and nonalcoholic fatty liver disease (NAFLD) in obese patients candidates for bariatric surgery. Patients were divided into three groups: eugonadal, untreated hypogonadal and symptomatic hypogonadal treated for 6-8 months with testosterone. BPH/LUTS parameters were assessed by IPSS (International Prostate Symptom Score) and prostate ultrasound. Preadipocyte cells (hPADs) isolated from adipose tissue biopsies were used to evaluate insulin sensitivity, adipogenic potential and mitochondrial function. NAFLD was evaluated by triglycerides (TG) assay and histological examination of liver biopsies. Clinically, notwithstanding a prostate volume increase, testosterone treatment improved the IPSS score and hyperemia. Liver TG levels correlated positively with both steatosis and NAS scores, and resulted significantly higher in hypogonadal patients when compared to eugonadal patients, with testosterone treatment significantly reducing TG levels. In the liver, testosterone treatment induced an increased mRNA expression of lipid metabolism markers, whereas in visceral adipose tissue it induced an increased mRNA expression of lipid catabolism and mitochondrial biofunctionality markers. In hPADs testosterone treatment induced an increased mRNA expression of brown adipogenesis and mitochondrial biofunctionality markers. Testosterone treatment normalized hPADs ability to respond to increasing concentrations of insulin. Accordingly, glucose uptake AUCs showed a positive correlation with testosterone levels. Hypogonadal hPADs mitochondria displayed a lower average length and a superoxide generation increase, compared to eugonadal, with testosterone treatment normalizing both parameters.