sildenafil-citrate and Overweight

To investigate that short-term treatment of sildenafil can induce browning of subcutaneous white adipose tissue (sWAT) in human adults.. A randomized, double-blinded, placebo-controlled, parallel group trial.. Sixteen eligibility overweight male subjects were recruited, comparing 100mg/day sildenafil versus an identical placebo therapy for 7days. sWAT samples were collected from subjects before and after 7-day sildenafil or placebo interventions.. The results showed that multilocular UCP1-positive adipocytes existed in sWAT samples from subjects after sildenafil treatment. Compared to before treatment in both group as well as after treatment in placebo, sildenafil significantly decreased adipocyte size, increased the expressions of UCP1 protein and mRNA, mitochondrial density, and leak respiratory capacity in sWAT (p<0.05). Sildenafil also increased plasma cyclic guanosine-3',5'-monophosphate (cGMP) and catecholamine concentrations (p<0.05), and consequently activated the expressions of vasodilator-stimulated phosphoprotein (VASP) and p70 ribosomal S6 kinase 1 (S6K1) (p<0.05). Sildenafil did not activate typical brown fat.. The current findings demonstrate that sildenafil can induce browning of sWAT in human, and this action may be through cGMP-dependent protein kinase I and mechanistic/mammalian target of rapamycin (mTOR) signaling pathways. Sldenafil may be a promising treatment for metabolic disease.

Topics: Adipocytes; Adipose Tissue, Brown; Adipose Tissue, White; Adult; Animals; Catecholamines; Cell Adhesion Molecules; Cyclic GMP-Dependent Protein Kinase Type I; Double-Blind Method; Humans; Male; Mice; Mice, Inbred C57BL; Microfilament Proteins; Mitochondria; Mitochondrial Proteins; Obesity; Overweight; Phosphoproteins; Signal Transduction; Sildenafil Citrate; Subcutaneous Fat; Uncoupling Protein 1; Young Adult

Sildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance.. The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function.. This was a randomized, double-blind, placebo-controlled study.. This trial was conducted at Vanderbilt Clinical Research Center.. Participants included overweight individuals with prediabetes.. Subjects were randomized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months. Subjects underwent a hyperglycemic clamp prior to and at the end of treatment.. The primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion.. Twenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per μU/mL*100 (95% confidence interval, 0.01 to 3.67 mg/kg/min per μU/mL*100; P = .049), after adjusting for baseline insulin sensitivity index and body mass index. In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion (P > .30). Sildenafil decreased plasminogen activator inhibitor-1 (P = .01), without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 μg/mg Cr. This effect persisted 3 months after sildenafil discontinuation.. Three-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function.

Topics: Adult; Albuminuria; Double-Blind Method; Endothelium, Vascular; Female; Fibrinolysis; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Hemodynamics; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Overweight; Phosphodiesterase 5 Inhibitors; Plasminogen Activator Inhibitor 1; Prediabetic State; Sildenafil Citrate

To evaluate the body mass index (BMI) and lower urinary tract symptom (LUTS) severity on treatment response to sildenafil in men with erectile dysfunction (ED) and moderate to severe LUTS associated with benign prostatic hyperplasia.. A post hoc analysis of data from a 12-week, double-blind, placebo-controlled study of sildenafil (50 mg once daily titrated to 100 mg once daily) was conducted. The BMI categories were obese (> or = 30 kg/m(2)), overweight (> or = 25 to < 30 kg/m(2)), and normal weight (< 25 kg/m(2)). ED was defined as a score of < or = 25 on the erectile function domain of the International Index of Erectile Function, and LUTS was defined by an International Prostate Symptom Score of > or = 12. The maximal urinary flow rate was determined by uroflowmetry.. Patients receiving sildenafil (n = 189) had a significant improvement in the erectile function domain scores of the International Index of Erectile Function (P < .0001 vs placebo, n = 180), which did not vary across BMI groups. A greater improvement in LUTS score was observed with sildenafil compared with placebo for men with severe LUTS (-8.6 vs -2.4, P < .0001) than in men with moderate LUTS (-3.6 vs -1.7, P = .06). Also, the improvement in LUTS scores was significant (P < or = .02) for men taking sildenafil independent of BMI (obese, -8.9 vs -5.4; overweight, -7.3 vs -3.2; normal weight, -7.1 vs -0.84). No difference was found among the treatment groups in the change from baseline maximal urinary flow rate across all LUTS and BMI categories (range 4.5 to -4.2 mL/s).. The results of our study have shown that daily dosing with sildenafil improved ED and LUTS independent of baseline LUTS severity or BMI.

Topics: Aged; Body Mass Index; Body Weight; Double-Blind Method; Erectile Dysfunction; Humans; Male; Middle Aged; Obesity; Overweight; Penile Erection; Piperazines; Placebos; Purines; Sildenafil Citrate; Sulfones; Urologic Diseases; Vasodilator Agents