scholarly journals Dietary AhR Ligands Regulate AhRR Expression in Intestinal Immune Cells and Intestinal Microbiota Composition

2020 ◽  
Vol 21 (9) ◽  
pp. 3189 ◽  
Author(s):  
Oliver Schanz ◽  
Rieka Chijiiwa ◽  
Sevgi Can Cengiz ◽  
Yasmin Majlesain ◽  
Heike Weighardt ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Immune Cells ◽  
High Fat Diet ◽  
Target Gene ◽  
Microbiota Composition ◽  
Wild Type ◽  
Aryl Hydrocarbon ◽  
Reporter Mice ◽  
Induced Changes ◽  
Deficient Mice

A diet rich in vegetables and fruit is generally considered healthy because of a high content of phytochemicals, vitamins, and fiber. The phytochemical indole-3-carbinol (I3C), a derivative of glucobrassicin, is sold as a dietary supplement promising diverse health benefits. I3C metabolites act as ligands of the aryl hydrocarbon receptor (AhR), an important sensor for environmental polyaromatic chemicals. Here, we investigated how dietary AhR ligand supplementation influences AhR target gene expression and intestinal microbiota composition. For this, we used AhR repressor (AhRR)-reporter mice as a tool to study AhR activation in the intestine following dietary I3C-supplementation in comparison with AhR ligand-deprived diets, including a high fat diet. AhRR expression in intestinal immune cells was mainly driven by dietary AhR ligands and was independent of microbial metabolites. A lack of dietary AhR ligands caused enhanced susceptibility to dextran sodium sulfate (DSS)-induced colitis and correlated with the expansion of Enterobacteriaceae, whereas Clostridiales, Muribaculaceae, and Rikenellaceae were strongly reduced. I3C supplementation largely reverted this effect. Comparison of I3C-induced changes in microbiota composition using wild-type (WT), AhRR-deficient, and AhR-deficient mice revealed both AhR-dependent and -independent alterations in the microbiome. Overall, our study demonstrates that dietary AhR ligand supplementation has a profound influence on Ahrr expression in intestinal immune cells as well as microbiota composition.

Aryl hydrocarbon receptor-deficient mice are protected from high fat diet-induced changes in metabolic rhythms

2017 ◽  
Vol 34 (3) ◽  
pp. 318-336 ◽  
Author(s):  
Cassie Jaeger ◽  
Canxin Xu ◽  
Mingwei Sun ◽  
Stacey Krager ◽  
Shelley A. Tischkau
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
High Fat Diet ◽  
High Fat ◽  
Aryl Hydrocarbon ◽  
Induced Changes ◽  
Deficient Mice

High-fat diet-induced changes in body mass and hypothalamic gene expression in wild-type and leptin-deficient mice

Endocrine ◽  
2008 ◽  
Vol 33 (2) ◽  
pp. 176-188 ◽  
Author(s):  
Kristy L. Townsend ◽  
Magen M. Lorenzi ◽  
Eric P. Widmaier
Keyword(s):  
Gene Expression ◽  
Body Mass ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Induced Changes ◽  
Deficient Mice

scholarly journals β-Elemene Suppresses Obesity-Induced Imbalance in the Microbiota-Gut-Brain Axis

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 704
Author(s):  
Yingyu Zhou ◽  
Wanyi Qiu ◽  
Yimei Wang ◽  
Rong Wang ◽  
Tomohiro Takano ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
High Fat Diet ◽  
Brain Regions ◽  
Cerebral Metabolites ◽  
The Central Nervous System ◽  
Cerebral Inflammation ◽  
Regulatory Effects ◽  
Induced Changes ◽  
Pearson Correlations ◽  
Glucose Cycle

As a kind of metabolically triggered inflammation, obesity influences the interplay between the central nervous system and the enteral environment. The present study showed that β-elemene, which is contained in various plant substances, had effects on recovering the changes in metabolites occurring in high-fat diet (HFD)-induced obese C57BL/6 male mice brains, especially in the prefrontal cortex (PFC) and hippocampus (HIP). β-elemene also partially reversed HFD-induced changes in the composition and contents of mouse gut bacteria. Furthermore, we evaluated the interaction between cerebral metabolites and intestinal microbiota via Pearson correlations. The prediction results suggested that Firmicutes were possibly controlled by neuron integrity, cerebral inflammation, and neurotransmitters, and Bacteroidetes in mouse intestines might be related to cerebral aerobic respiration and the glucose cycle. Such results also implied that Actinobacteria probably affected cerebral energy metabolism. These findings suggested that β-elemene has regulatory effects on the imbalanced microbiota-gut-brain axis caused by obesity and, therefore, would contribute to the future study in on the interplay between cerebral metabolites from different brain regions and the intestinal microbiota of mice.

scholarly journals 12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response

2012 ◽  
Vol 302 (6) ◽  
pp. E654-E665 ◽  
Author(s):  
Banumathi K. Cole ◽  
Norine S. Kuhn ◽  
Shamina M. Green-Mitchell ◽  
Kendall A. Leone ◽  
Rebekah M. Raab ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Pancreatic Islets ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Stress Markers ◽  
Deficient Mice

Central obesity is associated with chronic inflammation, insulin resistance, β-cell dysfunction, and endoplasmic reticulum (ER) stress. The 12/15-lipoxygenase enzyme (12/15-LO) promotes inflammation and insulin resistance in adipose and peripheral tissues. Given that obesity is associated with ER stress and 12/15-LO is expressed in adipose tissue, we determined whether 12/15-LO could mediate ER stress signals. Addition of 12/15-LO lipid products 12(S)-HETE and 12(S)-HPETE to differentiated 3T3-L1 adipocytes induced expression and activation of ER stress markers, including BiP, XBP-1, p-PERK, and p-IRE1α. The ER stress inducer, tunicamycin, upregulated ER stress markers in adipocytes with concomitant 12/15-LO activation. Addition of a 12/15-LO inhibitor, CDC, to tunicamycin-treated adipocytes attenuated the ER stress response. Furthermore, 12/15-LO-deficient adipocytes exhibited significantly decreased tunicamycin-induced ER stress. 12/15-LO action involves upregulation of interleukin-12 (IL-12) expression. Tunicamycin significantly upregulated IL-12p40 expression in adipocytes, and IL-12 addition increased ER stress gene expression; conversely, LSF, an IL-12 signaling inhibitor, and an IL-12p40-neutralizing antibody attenuated tunicamycin-induced ER stress. Isolated adipocytes and liver from 12/15-LO-deficient mice fed a high-fat diet revealed a decrease in spliced XBP-1 expression compared with wild-type C57BL/6 mice on a high-fat diet. Furthermore, pancreatic islets from 12/15-LO-deficient mice showed reduced high-fat diet-induced ER stress genes compared with wild-type mice. These data suggest that 12/15-LO activity participates in ER stress in adipocytes, pancreatic islets, and liver. Therefore, reduction of 12/15-LO activity or expression could provide a new therapeutic target to reduce ER stress and downstream inflammation linked to obesity.

scholarly journals Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin-deficient mice

2008 ◽  
Vol 295 (2) ◽  
pp. E331-E338 ◽  
Author(s):  
Neel S. Singhal ◽  
Rajesh T. Patel ◽  
Yong Qi ◽  
Yun-Sik Lee ◽  
Rexford S. Ahima
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Wild Type ◽  
The Metabolic Syndrome ◽  
Expression Of Genes ◽  
Similar Body ◽  
Deficient Mice

Resistin has been linked to components of the metabolic syndrome, including obesity, insulin resistance, and hyperlipidemia. We hypothesized that resistin deficiency would reverse hyperlipidemia in genetic obesity. C57Bl/6J mice lacking resistin [resistin knockout (RKO)] had similar body weight and fat as wild-type mice when fed standard rodent chow or a high-fat diet. Nonetheless, hepatic steatosis, serum cholesterol, and very low-density lipoprotein (VLDL) secretion were decreased in diet-induced obese RKO mice. Resistin deficiency exacerbated obesity in ob/ob mice, but hepatic steatosis was drastically attenuated. Moreover, the levels of triglycerides, cholesterol, insulin, and glucose were reduced in ob/ob-RKO mice. The antisteatotic effect of resistin deficiency was related to reductions in the expression of genes involved in hepatic lipogenesis and VLDL export. Together, these results demonstrate a crucial role of resistin in promoting hepatic steatosis and hyperlipidemia in obese mice.

scholarly journals Disassociation of insulin action and Akt/FOXO signaling in skeletal muscle of older Akt-deficient mice

2012 ◽  
Vol 303 (11) ◽  
pp. R1186-R1194 ◽  
Author(s):  
Thomas H. Reynolds ◽  
Erin Merrell ◽  
Nicholas Cinquino ◽  
Megan Gaugler ◽  
Lily Ng
Keyword(s):  
High Fat Diet ◽  
Insulin Action ◽  
Mrna Levels ◽  
Wild Type ◽  
Akt Phosphorylation ◽  
Protein Levels ◽  
Akt Isoforms ◽  
Forkhead Box ◽  
Gene Ablation ◽  
Deficient Mice

The purpose of the present study was to determine the effect of Akt gene ablation on Akt/Forkhead Box O (FOXO) signaling and atrogene expression. This was accomplished by studying wild-type (WT) and isoform-specific Akt knockout (Akt1−/− and Akt2−/−) mice. The ability of insulin to promote Akt phosphorylation on Ser473 was significantly lower in extensor digitorum longus (EDL) and soleus muscles from Akt1−/− and Akt2−/− mice compared with WT mice. Total Akt1 protein levels were significantly lower in EDL muscles of Akt2−/− mice compared with WT mice, a process that appears to be posttranscriptionally regulated as Akt1 mRNA levels were unchanged. The loss of Akt1 protein in EDL muscles of Akt2−/− mice does not appear to be due to insulin resistance because 4 mo of a high-fat diet failed to reduce Akt1 protein levels in muscles of WT mice. Although FOXO3a phosphorylation and atrogin-1 expression were unaltered in muscles of Akt1−/− and Akt2−/− mice, the expression of the atrogenes Bnip3 and gabarapl were significantly elevated in muscles of both Akt1 and Akt2 knockout mice. Finally, the expression of striated activator of Rho signaling was significantly increased in muscles of Akt2−/− mice compared with Akt1−/− and WT mice. Our results demonstrate that the ablation of Akt isoforms disassociates insulin action and Akt/FOXO signaling to atrogenes.

Vasorelaxant and antiaggregatory actions of the nitroxyl donor isopropylamine NONOate are maintained in hypercholesterolemia

2011 ◽  
Vol 301 (4) ◽  
pp. H1405-H1414 ◽  
Author(s):  
Michelle L. Bullen ◽  
Alyson A. Miller ◽  
Janahan Dharmarajah ◽  
Grant R. Drummond ◽  
Christopher G. Sobey ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
High Fat Diet ◽  
Plasma Cholesterol ◽  
Soluble Guanylyl Cyclase ◽  
Vascular Diseases ◽  
Normal Diet ◽  
Wild Type ◽  
Novel Treatments ◽  
Cholesterol Levels ◽  
Deficient Mice

Nitroxyl (HNO) displays pharmacological and therapeutic actions distinct from those of its redox sibling nitric oxide (NO∙). It remains unclear, however, whether the vasoprotective actions of HNO are preserved in disease. The ability of the HNO donor isopropylamine NONOate (IPA/NO) to induce vasorelaxation, its susceptibility to tolerance development, and antiaggregatory actions were compared with those of a clinically used NO∙ donor, glyceryl trinitrate (GTN), in hypercholesterolemic mice. The vasorelaxant and antiaggregatory properties of IPA/NO and GTN were examined in isolated carotid arteries and washed platelets, respectively, from male C57BL/6J mice [wild-type (WT)] maintained on either a normal diet (WT-ND) or high fat diet (WT-HFD; 7 wk) as well as apolipoprotein E-deficient mice maintained on a HFD (ApoE−/−-HFD; 7 wk). In WT-ND mice, IPA/NO (0.1–30 μmol/l) induced concentration-dependent vasorelaxation and inhibition of collagen (30 μg/ml)-stimulated platelet aggregation, which was predominantly soluble guanylyl cyclase/cGMP dependent. Compared with WT-HFD mice, ApoE−/−-HFD mice displayed an increase in total plasma cholesterol levels ( P < 0.001), vascular ( P < 0.05) and platelet ( P < 0.05) superoxide (O2·−) production, and reduced endogenous NO∙ bioavailability ( P < 0.001). Vasorelaxant responses to both IPA/NO and GTN were preserved in hypercholesterolemia, whereas vascular tolerance developed to GTN ( P < 0.001) but not to IPA/NO. The ability of IPA/NO (3 μmol/l) to inhibit platelet aggregation was preserved in hypercholesterolemia, whereas the actions of GTN (100 μmol/l) were abolished. In conclusion, the vasoprotective effects of IPA/NO were maintained in hypercholesterolemia and, thus, HNO donors may represent future novel treatments for vascular diseases.

scholarly journals Reduced colonic microbial diversity is associated with colitis in NHE3-deficient mice

2013 ◽  
Vol 305 (10) ◽  
pp. G667-G677 ◽  
Author(s):  
Claire B. Larmonier ◽  
Daniel Laubitz ◽  
Faihza M. Hill ◽  
Kareem W. Shehab ◽  
Leszek Lipinski ◽  
...  
Keyword(s):  
Critical Role ◽  
Mucosal Injury ◽  
Microbiota Composition ◽  
Wild Type ◽  
Microbial Composition ◽  
Epithelial Barrier Function ◽  
Qpcr Analysis ◽  
Enteric Infections ◽  
Inflammatory Bowel ◽  
Deficient Mice

Chronic inflammation and enteric infections are frequently associated with epithelial Na+/H+exchange (NHE) inhibition. Alterations in electrolyte transport and in mucosal pH associated with inflammation may represent a key mechanism leading to changes in the intestinal microbial composition. NHE3 expression is essential for the maintenance of the epithelial barrier function. NHE3−/−mice develop spontaneous distal chronic colitis and are highly susceptible to dextran sulfate (DSS)-induced mucosal injury. Spontaneous colitis is reduced with broad-spectrum antibiotics treatment, thus highlighting the importance of the microbiota composition in NHE3 deficiency-mediated colitis. We herein characterized the colonic microbiome of wild-type (WT) and NHE3−/−mice housed in a conventional environment using 454 pyrosequencing. We demonstrated a significant decrease in the phylogenetic diversity of the luminal and mucosal microbiota of conventional NHE3−/−mice compared with WT. Rederivation of NHE3−/−mice from conventional to a barrier facility eliminated the signs of colitis and decreased DSS susceptibility. Reintroduction of the conventional microflora into WT and NHE3−/−mice from the barrier facility resulted in the restoration of the symptoms initially described in the conventional environment. Interestingly, qPCR analysis of the microbiota composition in mice kept in the barrier facility compared with reconventionalized mice showed a significant reduction of Clostridia classes IV and XIVa. Therefore, the gut microbiome plays a prominent role in the pathogenesis of colitis in NHE3−/−mice, and, reciprocally, NHE3 also plays a critical role in shaping the gut microbiota. NHE3 deficiency may be a critical contributor to dysbiosis observed in patients with inflammatory bowel disease.

Sign in / Sign up

Export Citation Format

Share Document