RESUMO
OBJECTIVE: Previous studies have reported that polyphenol-rich extracts from various sources can prevent obesity and associated gastro-hepatic and metabolic disorders in diet-induced obese (DIO) mice. However, whether such extracts can reverse obesity-linked metabolic alterations remains unknown. In the present study, we aimed to investigate the potential of a polyphenol-rich extract from cranberry (CE) to reverse obesity and associated metabolic disorders in DIO-mice. METHODS: Mice were pre-fed either a Chow or a High Fat-High Sucrose (HFHS) diet for 13 weeks to induce obesity and then treated either with CE (200â¯mg/kg, Chowâ¯+â¯CE, HFHSâ¯+â¯CE) or vehicle (Chow, HFHS) for 8 additional weeks. RESULTS: CE did not reverse weight gain or fat mass accretion in Chow- or HFHS-fed mice. However, HFHSâ¯+â¯CE fully reversed hepatic steatosis and this was linked to upregulation of genes involved in lipid catabolism (e.g., PPARα) and downregulation of several pro-inflammatory genes (eg, COX2, TNFα) in the liver. These findings were associated with improved glucose tolerance and normalization of insulin sensitivity in HFHSâ¯+â¯CE mice. The gut microbiota of HFHSâ¯+â¯CE mice was characterized by lower Firmicutes to Bacteroidetes ratio and a drastic expansion of Akkermansia muciniphila and, to a lesser extent, of Barnesiella spp, as compared to HFHS controls. CONCLUSIONS: Taken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols.
Assuntos
Fígado Gorduroso/tratamento farmacológico , Resistência à Insulina , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Vaccinium macrocarpon/química , Aumento de Peso/efeitos dos fármacos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Polifenóis/análise , Polifenóis/uso terapêuticoRESUMO
We studied the nature and antimicrobial activity of ozonolysis transformation products (OTPs) of levofloxacin (LEV), a frequently detected fluoroquinolone antimicrobial in environmental waters. Two bioassays, the Kirby-Bauer test and the broth microdilution assay, were used to measure changes in the antimicrobial activity of solutions at low LEV to O3 molar ratios (2:1, 2:3 and 1:3) compared to solutions without added O3 (LEV:O3 1:0). The Kirby-Bauer test was not sensitive enough to detect significant differences in the growth inhibition zones in samples LEV:O3 2:1 and LEV:O3 1:0; however, the broth microdilution assay showed that bacterial growth inhibition was significantly lower (P<0.001) in the solutions exposed to O3. Loss of antimicrobial activity in LEV:O3 2:1 solutions of (48±16)% was in agreement with the concentration decrease of LEV of (36±3)% in those same samples. A method of identification of OTPs using XCMS Online was applied to LEV:O3 2:1 and 1:0 samples and indicated the presence of an OTP of LEV of formula C18H20O5N3F, which was identified as LEV-N-oxide. The molecular structure of this compound was partially confirmed by tandem mass spectrometry experiments. This study showed that even at sub-optimal ozone doses, OTPs of higher antimicrobial activity than LEV were not formed.