6 research outputs found
Gut Microbiota Modulation Attenuated the Hypolipidemic Effect of Simvastatin in High-Fat/Cholesterol-Diet Fed Mice
The hypolipidemic effect of simvastatin
varies greatly among patients.
In the current study, we investigated the gut microbial-involved mechanisms
underlying the different responses to simvastatin. Male C57BL/6J mice
were divided into control (Con), high-fat/cholesterol diet (HFD),
antibiotic (AB), simvastatin (SV) and antibiotic_simvastatin (AB_SV)
groups, respectively. At the end of the experiment, serum samples
were collected for lipids and metabolomic analysis, and liver tissues
for histology, gene and protein expression analysis. The results showed
that antibiotic treatment not only altered the composition of gut
microbiota, but attenuated the hypolipidemic effect of SV. A total
of 16 differential metabolites between SV and HFD groups were identified
with metabolomics, while most of them showed no statistical differences
between AB_SV and HFD groups, and similar changes were also observed
in bile acids profile. The expressions of several genes and proteins
involved in regulating bile acids synthesis were significantly reversed
by SV, but not AB_SV in HFD fed mice. In summary, our current study
indicated that the hypolipidemic effect of SV was correlated with
the composition of the gut microbiota, and the attenuated hypolipidemic
effect of SV by gut microbiota modulation was associated with a suppression
of bile acids synthesis from cholesterol
Metabolic Transformation of DMBA-Induced Carcinogenesis and Inhibitory Effect of Salvianolic Acid B and Breviscapine Treatment
Oral cancer typically develops from hyperplasia through
dysplasia
to carcinoma with a multistep process of carcinogenesis involving
genetic alterations resulting in aberrant cellular appearance, deregulated
cell growth, and carcinoma. The metabolic transformation during the
process of oral carcinogenesis and its implications for cancer therapy
have not been extensively investigated. Here, we report a metabonomic
study on a classical model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced
oral carcinogenesis in hamsters to delineate characteristic metabolic
transformation during the carcinogenesis using gas chromatography
time-of-flight mass spectrometry (GC–TOF MS). Salvianolic acid
B (Sal-B), isolated from <i>Salvia miltiorrhiza</i> Bge, and Breviscapine,
a flavonoid isolated from Herba Erigerontis, were used to treat the
hamsters exposed to DMBA to investigate the molecular mechanism of
the inhibitory effect of the two agents on oral carcinogenesis. The
dynamic changes of serum metabolic profiles indicated that both Sal-B
and Breviscapine were able to attenuate DMBA-induced metabolic perturbation,
which is consistent with the histopathological findings that Sal-B
and Breviscapine significantly decreased the squamous cell carcinoma
(SCC) incidence in the two treatment groups. Significant alterations
of key metabolic pathways, including elevated glutaminolysis and glycolysis,
and decreased cholesterol and myo-inositol metabolism, were observed
in the DMBA-induced model group, which were attenuated or normalized
by Sal-B or Breviscapine treatment. Elevated inflammation and tumor
angiogenesis at gene and metabolite expression levels were also observed
in DMBA-induced oral dysplasia and SCC but were attenuated or normalized
by Sal-B and Breviscapine along with significantly decreased incidences
of SCC formation
High Fat Diet and High Sucrose Intake Divergently Induce Dysregulation of Glucose Homeostasis through Distinct Gut Microbiota-Derived Bile Acid Metabolism in Mice
A high
calorie diet such as excessive fat and sucrose intake is
always accompanied by impaired glucose homeostasis such as T2DM (type
2 diabetes mellitus). However, it remains unclear how fat and sucrose
individually affect host glucose metabolism. In this study, mice were
fed with high fat diet (HFD) or 30% sucrose in drinking water (HSD)
for 24 weeks, and glucose metabolism, gut microbiota composition,
as well as bile acid (BA) profile were investigated. In addition,
the functional changes of HFD or HSD-induced gut microbiota were further
verified by fecal microbiota transplantation (FMT) and ex
vivo culture of gut bacteria with BAs. Our results showed
that both HFD and HSD caused dysregulated lipid metabolism, while
HFD feeding had a more severe effect on impaired glucose homeostasis,
accompanied by reduced hyocholic acid (HCA) levels in all studied
tissues. Meanwhile, HFD had a more dramatic influence on composition
and function of gut microbiota based on α diversity indices,
β diversity analysis, as well as the abundance of secondary
BA producers than HSD. In addition, the phenotypes of impaired glucose
homeostasis and less formation of HCA caused by HFD can be transferred
to recipient mice by FMT. Ex vivo culture with gut
bacteria and BAs revealed HFD-altered gut bacteria produced less HCA
than HSD, which might closely associate with reduced relative abundance
of C7 epimerase-coding bacteria g_norank/unclassified_f_Eggerthellaceae and bile salt hydrolase-producing bacteria Lactobacillus and Bifidobacterium in HFD group. Our findings
revealed that the divergent effects of different high-calorie diets
on glucose metabolism may be due to the gut microbiota-mediated generation
and metabolism of BAs, highlighting the importance of dietary management
in T2DM
Transcriptomic and Metabonomic Profiling Reveal Synergistic Effects of Quercetin and Resveratrol Supplementation in High Fat Diet Fed Mice
Dietary quercetin and resveratrol have been frequently
used in treating various diseases, but the underlying mechanisms are
not entirely clear. Here, we report combined transcriptomic and metabonomic
profiling that showed that the combined supplementation with quercetin
and resveratrol produced synergistic effects on a high-fat diet-induced
metabolic phenotype in mice. Histological and phenotypic improvements
in serum and hepatic total cholesterol, insulin, fasting blood glucose,
and HbA1c were also observed in mice receiving combined quercetin
and resveratrol supplementation. This combined quercetin and resveratrol
supplementation resulted in significant restoration of gene sets in
functional pathways of glucose/lipid metabolism, liver function, cardiovascular
system, and inflammation/immunity, which were altered by high fat
diet feeding. The integration of transcriptomic and metabonomic data
indicated quercetin and resveratrol supplementation enhanced processes
of glycolysis and fatty acid oxidation, as well as suppressed gluconeogenesis.
These alterations discovered at both the transcriptional and metabolic
levels highlight the significance of combined “omics”
platforms for elucidating mechanistic pathways altered by dietary
polyphenols, such as quercetin and resveratrol, in a synergistic manner
Transcriptomic and Metabonomic Profiling Reveal Synergistic Effects of Quercetin and Resveratrol Supplementation in High Fat Diet Fed Mice
Dietary quercetin and resveratrol have been frequently
used in treating various diseases, but the underlying mechanisms are
not entirely clear. Here, we report combined transcriptomic and metabonomic
profiling that showed that the combined supplementation with quercetin
and resveratrol produced synergistic effects on a high-fat diet-induced
metabolic phenotype in mice. Histological and phenotypic improvements
in serum and hepatic total cholesterol, insulin, fasting blood glucose,
and HbA1c were also observed in mice receiving combined quercetin
and resveratrol supplementation. This combined quercetin and resveratrol
supplementation resulted in significant restoration of gene sets in
functional pathways of glucose/lipid metabolism, liver function, cardiovascular
system, and inflammation/immunity, which were altered by high fat
diet feeding. The integration of transcriptomic and metabonomic data
indicated quercetin and resveratrol supplementation enhanced processes
of glycolysis and fatty acid oxidation, as well as suppressed gluconeogenesis.
These alterations discovered at both the transcriptional and metabolic
levels highlight the significance of combined “omics”
platforms for elucidating mechanistic pathways altered by dietary
polyphenols, such as quercetin and resveratrol, in a synergistic manner
Transcriptomic and Metabonomic Profiling Reveal Synergistic Effects of Quercetin and Resveratrol Supplementation in High Fat Diet Fed Mice
Dietary quercetin and resveratrol have been frequently
used in treating various diseases, but the underlying mechanisms are
not entirely clear. Here, we report combined transcriptomic and metabonomic
profiling that showed that the combined supplementation with quercetin
and resveratrol produced synergistic effects on a high-fat diet-induced
metabolic phenotype in mice. Histological and phenotypic improvements
in serum and hepatic total cholesterol, insulin, fasting blood glucose,
and HbA1c were also observed in mice receiving combined quercetin
and resveratrol supplementation. This combined quercetin and resveratrol
supplementation resulted in significant restoration of gene sets in
functional pathways of glucose/lipid metabolism, liver function, cardiovascular
system, and inflammation/immunity, which were altered by high fat
diet feeding. The integration of transcriptomic and metabonomic data
indicated quercetin and resveratrol supplementation enhanced processes
of glycolysis and fatty acid oxidation, as well as suppressed gluconeogenesis.
These alterations discovered at both the transcriptional and metabolic
levels highlight the significance of combined “omics”
platforms for elucidating mechanistic pathways altered by dietary
polyphenols, such as quercetin and resveratrol, in a synergistic manner