Endocrine Abstracts

Visceral adipose tissue (VAT) dysfunction is closely associated with the rising incidence of cardiovascular diseases (CVD) and type 2 diabetes mellitus. Two distinct types of adipose tissue, white (WAT) and brown (BAT), are present in mammals. Development of ‘brown-like’ adipocytes within white adipose tissue has potential antiobesity and insulin-sensitizing effects. Genetic manipulation of cGMP formation suggests a new role for this pathway in preadipocytes commitment. We have recently demonstrated that the selective phosphodiesterase type 5 (PDE5) inhibitor, tadalafil, by increasing cGMP signaling, reduced visceral adiposity (VAT) and triglycerides level in a high-fat diet (HFD)-induced rabbit model of metabolic syndrome (MetS). Herein, we investigated the effects of in vivo tadalafil dosing (2 mg/kg per day, for 1 week) on liver, VAT, and the adipogenic capacity on isolated VAT preadipocytes (rPADs) from rabbits fed a HFD (with or w/o tadalafil) or regular diet (RD). Results: Adipocyte size, tissue hypoxia, and the expression of cytosolic insulin-regulated glucose transporter GLUT4 were significantly increased in VAT isolated from the HFD rabbits, and normalized by in vivo tadalafil dosing. The circulating level and liver expression of TNFα was also increased in HFD rabbits and decreased by in vivo tadalafil dosing. rPADs isolated from the HFD rabbits were less sensitive to insulin, as demonstrated by the decreased insulin-induced glucose uptake, triglyceride synthesis, and adipogenic capacity, as well as by the impaired fusion of lipid droplets. In vivo tadalafil dosing preserved all the aforementioned metabolic alterations. Expression of UCP-1 was in vivo (VAT) and in vitr (rPAD) increased by tadalafil, which partially stimulates preadipocyte differentiation towards a brown-like phenotype.

In conclusion, Tadalafil dosing in a MetS rabbit model ameliorates liver and VAT MetS-induced alterations. This could reflect the ability of tadalafil to restore insulin sensitivity in VAT unable to finalize its storage function, counteracting MetS-induced liver alterations.