Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome

2012 ◽  
Vol 132 (1-2) ◽  
pp. 80-92 ◽  
Author(s):  
Annamaria Morelli ◽  
Paolo Comeglio ◽  
Sandra Filippi ◽  
Erica Sarchielli ◽  
Ilaria Cellai ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Receptor Agonist ◽  
Rabbit Model ◽  
Farnesoid X Receptor ◽  
High Fat

scholarly journals Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit

2011 ◽  
Vol 212 (1) ◽  
pp. 71-84 ◽  
Author(s):  
Linda Vignozzi ◽  
Annamaria Morelli ◽  
Erica Sarchielli ◽  
Paolo Comeglio ◽  
Sandra Filippi ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Visceral Obesity ◽  
Immunohistochemical Analysis ◽  
Farnesoid X Receptor ◽  
Standard Diet ◽  
High Fat ◽  
Prostate Inflammation ◽  
Urinary Tract Symptoms ◽  
Lower Urinary

Metabolic syndrome (MetS) and benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) are often associated. One of their common denominators is hypogonadism. However, testosterone supplementation is limited by concerns for potential prostatic side effects. The objective was to determine whether MetS-associated prostate alterations are prevented by testosterone supplementation. We used a previously described animal model of MetS, obtained by feeding male rabbits a high-fat diet (HFD) for 12 weeks. Subsets of HFD rabbits were treated with testosterone or with the farnesoid X receptor agonist INT-747. Rabbits fed a standard diet were used as controls. HFD-animals develop hypogonadism and all the MetS features: hyperglycemia, glucose intolerance, dyslipidemia, hypertension, and visceral obesity. In addition, HFD-animals show a prostate inflammation. Immunohistochemical analysis demonstrated that HFD-induced prostate fibrosis, hypoxia, and inflammation. The mRNA expression of several proinflammatory (IL8, IL6, IL1β, and TNFα), T lymphocyte (CD4, CD8, Tbet, Gata3, and ROR γt), macrophage (TLR2, TLR4, and STAMP2), neutrophil (lactoferrin), inflammation (COX2 and RAGE), and fibrosis/myofibroblast activation (TGFβ, SM22α, αSMA, RhoA, and ROCK1/ROCK2) markers was significantly increased in HFD prostate. Testosterone, as well as INT-747, treatment prevented some MetS features, although only testosterone normalized all the HFD-induced prostate alterations. Interestingly, the ratio between testosterone and estradiol plasma level retains a significant, negative, association with all the fibrosis and the majority of inflammatory markers analyzed. These data highlight that testosterone protects rabbit prostate from MetS-induced prostatic hypoxia, fibrosis, and inflammation, which can play a role toward the development/progression of BPH/LUTS.

scholarly journals Prosopis alba seed flour improves vascular function in a rabbit model of high fat diet-induced metabolic syndrome

Heliyon ◽  
2019 ◽  
Vol 5 (8) ◽  
pp. e01967 ◽  
Author(s):  
Florencia Cattaneo ◽  
Julieta Roco ◽  
Gabriela Alarcón ◽  
María Inés Isla ◽  
Susana Jeréz
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Vascular Function ◽  
Rabbit Model ◽  
High Fat ◽  
Prosopis Alba ◽  
Seed Flour

scholarly journals The dual FXR/TGR5 agonist INT-767 counteracts nonalcoholic steatohepatitis in a rabbit model of high fat diet-induced metabolic syndrome

2016 ◽  
Author(s):  
Linda Vignozzi ◽  
Ilaria Cellai ◽  
Sandra Filippi ◽  
Paolo Comeglio ◽  
Erica Sarchielli ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Rabbit Model ◽  
High Fat

Effects of dietary n-3 PUFA levels in early life on susceptibility to high-fat-diet-induced metabolic syndrome in adult mice

2020 ◽  
pp. 108578
Author(s):  
Dan-Dan Wang ◽  
Fang Wu ◽  
Ling-Yu Zhang ◽  
Ying-Cai Zhao ◽  
Cheng-Cheng Wang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Early Life ◽  
High Fat ◽  
Adult Mice

scholarly journals Treatment potential of LPCN 1144 on liver health and metabolic regulation in a non-genomic, high fat diet induced NASH rabbit model

2021 ◽  
Author(s):  
P. Comeglio ◽  
E. Sarchielli ◽  
S. Filippi ◽  
I. Cellai ◽  
G. Guarnieri ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
High Fat Diet ◽  
Metabolic Regulation ◽  
Therapeutic Potential ◽  
Rabbit Model ◽  
Free Testosterone ◽  
Preclinical Model ◽  
High Fat ◽  
Liver Health ◽  
Metabolic Dysfunctions

Abstract Purpose Low free testosterone (T) level in men is independently associated with presence and severity of Non-Alcoholic Steatohepatitis (NASH). The histological and molecular effects of oral testosterone prodrug LPCN 1144 treatment on hepatic fibrosis and NASH features are unknown. A metabolic syndrome-induced NASH model in rabbits consuming high fat diet (HFD) has been previously used to assess treatment effects of injectable T on hepatic fibrosis and NASH features. Here we present results on LPCN 1144 in this HFD-induced, NASH preclinical model. Methods Male rabbits were randomly assigned to five groups: regular diet (RD), HFD, HFD + 1144 vehicle (HFD + Veh), HFD + 1144 (1144), and HFD + 1144 + α-tocopherol (1144 + ALPHA). Rabbits were sacrificed after 12 weeks for liver histological, biochemical and genetic analyses. Histological scores were obtained through Giemsa (inflammation), Masson’s trichrome (steatosis and ballooning), and Picrosirius Red (fibrosis) staining. Results Compared to RD, HFD and HFD + Veh significantly worsened NASH features and hepatic fibrosis. Considering HFD and HFD + Veh arms, histological and biomarker features were not significantly different. Both 1144 and 1144 + ALPHA arms improved mean histological scores of NASH as compared to HFD arm. Importantly, percentage of fibrosis was improved in both 1144 (p < 0.05) and 1144 + ALPHA (p = 0.05) treatment arms vs. HFD. Both treatment arms also reduced HFD-induced inflammation and fibrosis mRNA markers. Furthermore, 1144 treatments significantly improved HFD-induced metabolic dysfunctions. Conclusions Histological and biomarker analyses demonstrate that LPCN 1144 improved HFD-induced hepatic fibrosis and NASH biochemical, biomolecular and histochemical features. These preclinical findings support a therapeutic potential of LPCN 1144 in the treatment of NASH and of hepatic fibrosis.

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