Testosterone supplementation improves adipose tissue function in an animal model of metabolic syndrome

A Morelli; E Maneschi; L Vignozzi; S Filippi; M Marchetta; B Mazzanti; A Calcagno; P Comeglio; I Cellai; G B Vannelli; M Maggi

Introduction: Adipose tissue dysfunction is associated to metabolic syndrome (MetS), a clustering of cardio-metaboilic risk factors, including hypogonadism. We recently demonstrated that T supplementation was able to ameliorate the metabolic profile and reduce visceral fat accumulation in high-fat diet (HFD)-induced rabbit model of MetS.

Methods: We evaluated the differentiation capacity of preadipocytes (rPAD) obtained from visceral fat of the following rabbit groups: HFD (rPAD-HFD), T-supplemented HFD-rabbits (rPAD-T), standard diet (rPADcontrol) and HFD treated with INT-747 (rPAD-I), an agonist of the nuclear receptor FXR which previously showed the ability to reduce visceral fat accumulation in HFD-rabbits. rPAD were exposed to differentiating mixture (DIM) for 10 days and adipogenic potential was evaluated by quantitative analysis of trygliceride content and expression of adipocyte-specific genes.

Results: Histomorphometric analysis of visceral fat sections from all groups evidenced that adipocyte size was significantly increased in HFD-rabbit compared to control, indicating adipocyte dysfunction. Accordingly, rPAD-HFD showed a reduced capacity to accumulate triglyceride when exposed to DIM (84% over untreated cells) in comparison with rPADcontrol (318%). Moreover, glucose uptake in response to insulin was also reduced in rPAD-HFD. Interestingly, visceral adipocyte size was normalized in both T-and INT747-treated HFD rabbits. Functionally, rPAD-T and rPAD-I showed a triglyceride accumulation capacity after DIM (247 and 129%, respectively) and a glucose uptake ability comparable to that of rPADcontrol.

These findings were confirmed in terms of mRNA expression of adipocyte-specific genes (DKK1, FABP4, adiponectin and leptin), which were significantly induced in rPADcontrol, rPAD-T and rPAD-I, while remained unchanged in rPAD-HFD after exposure to DIM.

Conclusion: Overall, our results indicate that T-supplementation in the animal model of MetS may positively affect adipose tissue functions through the restoration of adipocyte commitment. This could reflect the ability of T in counteracting metabolic alterations most likely restoring adiponectin and insulin sensitivity in experimental MetS.

Endocrine Abstracts

P350