Characterization of liver changes in ZSF1 rats, an animal model of metabolic syndrome

Borges‐Canha, Marta; Portela-Cidade, José Pedro; Conceição, Glória; Sousa-Mendes, Cláudia; Leite, Sara; Fontoura, Dulce; Moreira-Gonçalves, Daniel; Falcão-Pires, Inês; Lourenço, André P.; Leite‐Moreira, Adelino F.; Pimentel‐Nunes, Pedro

doi:10.17235/reed.2017.4575/2016

Cited by 11 publications

(8 citation statements)

References 41 publications

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“…For each bacterial group in the PCA biplot diagram (Figure D), the length of the line is directly proportional to contribution and the direction of the line indicates the time point that bacterial group contributed to. At the level of family, GTL significantly increased the SCFA‐producing Lachinospiraceae and Ruminococcaceae , elevated Erysipelotrichaceae and Bifidobacteriaceae and Coriobacteriaceae and decreased Prevotellaceae (Figure I–O) . Notably, the GTL effect on Ruminococcaceae and Bifidobacteriaceae were irreversible (Figure K,M).…”

Section: Resultsmentioning

confidence: 97%

Green Tea Liquid Consumption Alters the Human Intestinal and Oral Microbiome

Yuan

Long

et al. 2018

Molecular Nutrition Food Res

110

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ScopeGTPs (green tea polyphenols) exert anti‐CRC (colorectal cancer) activity. The intestinal microbiota and intestinal colonization by bacteria of oral origin has been implicated in colorectal carcinogenesis. GT modulates the composition of mouse gut microbiota harmonious with anticancer activity. Therefore, the effect of green tea liquid (GTL) consumption on the gut and oral microbiome is investigated in healthy volunteers (n = 12).Methods and results16S sequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis of both fecal and saliva samples (collected before intervention, after 2 weeks of GTL (400 mL per day) and after a washout period of one week) in healthy volunteers show changes in microbial diversity and core microbiota and difference in clear classification (partial least squares‐discriminant analysis [PLS‐DA]). An irreversible, increased FIR:BAC (Firmicutes to Bacteroidetes ratio), elevated SCFA producing genera, and reduction of bacterial LPS synthesis in feces are discovered in response to GTL. GTL alters the salivary microbiota and reduces the functional pathways abundance relevance to carcinogenesis. Similar bacterial networks in fecal and salivary microbiota datasets comprising putative oral bacteria are found and GTL reduces the fecal levels of Fusobacterium. Interestingly, both Lachnospiraceae and B/E (Bifidobacterium to Enterobacteriacea ratio—markers of colonization resistance [CR]) are negatively associated with the presence of oral‐like bacterial networks in the feces.ConclusionThese results suggest that GTL consumption causes both oral and gut microbiome alterations.

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Section: Resultsmentioning

confidence: 97%

Green Tea Liquid Consumption Alters the Human Intestinal and Oral Microbiome

Yuan

Long

et al. 2018

Molecular Nutrition Food Res

110

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“…Although the obese ZSF1 rat is not a model of liver disease per se, this model is known to develop steatosis with age, typically beginning around 20-24 weeks (Zambad et al, 2011;Borges Canha et al, 2017). As a model of diabetes, disease progression may reflect that seen in humans with type 2 diabetes who develop increasingly severe comorbidities.…”

Section: Olinciguat Treatment Affected Cardiometabolic Risk Factors Amentioning

confidence: 99%

Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

et al. 2020

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Nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic 3',5' GMP (cGMP) signaling plays a central role in regulation of diverse processes including smooth muscle relaxation, inflammation, and fibrosis. sGC is activated by the short-lived physiologic mediator NO. sGC stimulators are small-molecule compounds that directly bind to sGC to enhance NOmediated cGMP signaling. Olinciguat, (R)-3,3,3-trifluoro-2-(((5-fluoro-2-(1-(2fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyrimidin-4-yl)amino)methyl)-2hydroxypropanamide, is a new sGC stimulator currently in Phase 2 clinical development. To understand the potential clinical utility of olinciguat, we studied its pharmacokinetics, tissue distribution, and pharmacologic effects in preclinical models. Olinciguat relaxed human vascular smooth muscle and was a potent inhibitor of vascular smooth muscle proliferation in vitro. These antiproliferative effects were potentiated by the phosphodiesterase 5 inhibitor tadalafil, which did not inhibit vascular smooth muscle proliferation on its own. Olinciguat was orally bioavailable and predominantly cleared by the liver in rats. In a rat whole body autoradiography study, olinciguat-derived radioactivity in most tissues was comparable to plasma levels, indicating a balanced distribution between vascular and extravascular compartments. Olinciguat was explored in rodent models to study its effects on the vasculature, the heart, the kidneys, metabolism, and inflammation. Olinciguat reduced blood pressure in normotensive and hypertensive rats. Olinciguat was cardioprotective in the Dahl rat salt-sensitive hypertensive heart failure model. In the rat ZSF1 model of diabetic nephropathy and metabolic syndrome, olinciguat was renoprotective and associated with lower circulating glucose, cholesterol, and triglycerides. In a mouse TNFa-induced inflammation model, olinciguat treatment was associated with lower levels of endothelial and leukocyte-derived soluble adhesion

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“…This suggests that the general bifidogenic effect observed upon inulin consumption can also be observed upon the consumption of inulin incorporated into a processed meat product. Earlier findings have revealed that bifidobacteria reduced azoxymethane‐induced colon carcinogenesis in rats and studies have indicated associations between colorectal cancer and diminished levels of bifidobacteria in the gut . At the genus level, an increased relative abundance of an unclassified Lachnospiraceae was found after the consumption of inulin‐enriched sausages compared to control sausages.…”

Section: Discussionmentioning

confidence: 91%