Tadalafil reduces visceral adipose tissue accumulation by promoting preadipocytes differentiation towards a metabolically healthy phenotype: Studies in rabbits

Maneschi, Elena; Cellai, Ilaria; Aversa, Antônio; Mello, Tommaso; Filippi, Sandra; Comeglio, Paolo; Bani, Danièle; Guasti, Daniele; Sarchielli, Erica; Salvatore, Giulia; Morelli, Annamaria; Mazzanti, Benedetta; Corcetto, Francesca; Corno, C.; Francomano, Davide; Galli, Andrea; Vannelli, Gabriella Barbara; Lenzi, Andrea; Mannucci, Edoardo; Maggi, Mario; Vignozzi, Linda

doi:10.1016/j.mce.2016.01.015

Cited by 25 publications

(39 citation statements)

References 71 publications

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“…In men with erectile dysfunction (ED) chronic PDE 5 i improves insulin secretion, [6] endothelial function, [7] and in vitro it regulates aromatase (ARO) expression both in adipocyte [8] and osteoblast cell models. [9] Interestingly, data from experimental rabbit model of high fat diet-induced metabolic syndrome (MetS) confirms that tadalafil (TAD) administration not only after long-term (12 weeks), but even after a short-term exposure (1 week), in vivo and in vitro, was able to restore a correct pre-adipocyte commitment, through a positive effect on insulin sensitivity, and to upregulate, via PKG activation, the genes related to mitochondrial biogenesis and brown adipogenesis, including UCP 1 [10]. Studies in men with type-2 diabetes (T 2 D) confirmed that chronic sildenafil administration was able to reduce epicardial adipose tissue and in a murine diabetic model regulated visceral adiposity by shifting adipose tissue cell composition toward a less inflamed profile [11].…”

Section: Introductionmentioning

confidence: 85%

Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization

et al. 2017

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Section: Introductionmentioning

confidence: 85%

Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization

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“…PDE5 inhibitors are widely prescribed for erectile dysfunction, pulmonary hypertension, and low urinary trait syndrome (102). Of interest, PDE5 inhibitors have been recently shown to determine brownconversionofWATinpreclinicalstudies,andtheir potential BAT-inducing actions await demonstration in human studies (101,103).…”

Section: Pharmacologic Control Of Browningmentioning

confidence: 99%

Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte

et al. 2017

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The metabolic syndrome (MetS) is defined as a cluster of 3 or more metabolic and cardiovascular risk factors and represents a serious problem for public health. Altered function of adipose tissue has a significant impact on whole-body metabolism and represents a key driver for the development of these metabolic derangements, collectively referred as to MetS. In particular, increased visceral and ectopic fat deposition play a major role in the development of insulin resistance and MetS. A large body of evidence demonstrates that aging and MetS share several metabolic alterations. Of importance, molecular pathways that regulate lifespan affect key processes of adipose tissue physiology, and transgenic mouse models with adipose-specific alterations in these pathways show derangements of adipose tissue and other metabolic features of MetS, which highlights a causal link between dysfunctional adipose tissue and deleterious effects on whole-body homeostasis. This review analyzes adipose tissue-specific dysfunctions, including metabolic alterations that are related to aging, that have a significant impact on the development of MetS.-Armani, A., Berry, A., Cirulli, F., Caprio, M. Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte.

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“…This study provides further evidence of the involvement of PDE5 inhibition in preserving the quality of AT by limiting AT inflammation and promoting healthier fat deposits, and expands our understanding of the relationship between inflammatory signaling pathways and adipose tissue function.APs are functionally plastic cells that are influenced by their physiologic context. Recently, a study on a high-fat diet rabbit model demonstrated that the PDE5i, tadalafil, promoted preadipocyte differentiation, improving AT(Maneschi et al, 2016). Correlation between VAT (g) (a) and SAT (g) (b) with body weight change from baseline (g) in vehicle-treated (black) or sildenafiltreated mice (gray); db/db + vehicle, n = 9; db/db + sildenafil, n = 9.…”

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confidence: 99%

Chronic phosphodiesterase type 5 inhibition has beneficial effects on subcutaneous adipose tissue plasticity in type 2 diabetic mice

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Gianfrilli

Cardarelli

et al. 2018

Journal Cellular Physiology

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Different adipose tissue (AT) depots are associated with multiple metabolic risks. Phosphodiesterase type 5 (PDE5) is involved in adipocyte physiology and PDE5 inhibition may affect adipogenesis and ameliorate white AT quality. The aim of this study is to investigate the distribution of AT and the composition of the stroma-vascular fraction (SVF) of subcutaneous AT (SAT) in type 2 diabetic mice after prolonged treatment with a PDE5 inhibitor, Sildenafil. 18 db/db mice were treated with Sildenafil or vehicle for 12 weeks. AT distribution was monitored and SAT was processed for isolation of SVF by flow cytometry. Sildenafil induced an overall reduction in AT, mainly in visceral AT (VAT), compared with SAT. In Sildenafil-treated mice, the mean change in body weight from baseline positively correlated with VAT, but not with SAT. Characterization of SVF of SAT showed an increase in the frequency of M2 macrophages and endothelial cells in treated mice. Sildenafil improved the maintenance of SAT homeostasis and distribution.

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Tadalafil reduces visceral adipose tissue accumulation by promoting preadipocytes differentiation towards a metabolically healthy phenotype: Studies in rabbits

Cited by 25 publications

References 71 publications

Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization

Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization

Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte

Chronic phosphodiesterase type 5 inhibition has beneficial effects on subcutaneous adipose tissue plasticity in type 2 diabetic mice

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