Tempol Treatment Response Study
Objective: Evaluation of tempol's anti-obesity effects and dependence on intestinal FXR signaling, demonstrating that tempol reduces obesity by altering the gut microbiome and inhibiting intestinal farnesoid X receptor signaling
This is a Tempol Treatment Response Study protocol using mouse as the model organism. The procedure involves 6 procedural steps, 2 materials. Extracted from a 2013 paper published in Nature Communications.
Model and subjects
mouse • Not explicitly stated in provided text • unknown • Not explicitly stated in provided text • Not explicitly stated in provided text
Study window
Estimated timing pending
Core workflow
Tempol treatment administration • Microbiome analysis • Bile acid measurement
Primary readouts
- Obesity/weight gain reduction
- Gut microbiome composition changes
- Lactobacillus genus abundance
- Bile salt hydrolase (BSH) activity
Key equipment and reagents
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Protocol Steps
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Tempol treatment administration
Administer tempol to wild-type mice to evaluate anti-obesity effects and microbiome alterations
Note: Tempol treatment alters the gut microbiome by preferentially reducing the genus Lactobacillus
View evidence from paper
“The antioxidant tempol reduces obesity in mice. Here we show that tempol alters the gut microbiome”
Microbiome analysis
Analyze changes in gut microbiome composition, specifically measuring reduction in Lactobacillus genus and bile salt hydrolase (BSH) activity
Note: Tempol preferentially reduces Lactobacillus and its BSH activity, leading to accumulation of intestinal tauro-β-muricholic acid (T-β-MCA)
View evidence from paper
“tempol alters the gut microbiome by preferentially reducing the genus Lactobacillus and its bile salt hydrolase (BSH) activity”
Bile acid measurement
Measure intestinal tauro-β-muricholic acid (T-β-MCA) accumulation as a result of reduced BSH activity
Note: T-β-MCA is an FXR nuclear receptor antagonist involved in regulation of bile acid, lipid and glucose metabolism
View evidence from paper
“leading to the accumulation of intestinal tauro-β-muricholic acid (T-β-MCA). T-β-MCA is an farnesoid X receptor (FXR) nuclear receptor antagonist”
FXR signaling assessment
Evaluate FXR signaling inhibition in the intestine during tempol treatment
Note: Increased T-β-MCA levels during tempol treatment inhibit FXR signaling in the intestine
View evidence from paper
“Its increased levels during tempol treatment inhibit FXR signalling in the intestine”
High-fat diet feeding of Fxr ΔIE mice
Feed intestine-specific Fxr-null (Fxr ΔIE) mice a high-fat diet and measure diet-induced obesity
Note: Fxr ΔIE mice show lower diet-induced obesity similar to tempol-treated wild-type mice
View evidence from paper
“High-fat diet-fed intestine-specific Fxr-null (Fxr ΔIE) mice show lower diet-induced obesity, similar to tempol-treated wild-type mice”
Tempol treatment of Fxr ΔIE mice
Administer tempol to intestine-specific Fxr-null (Fxr ΔIE) mice to determine if intestinal FXR mediates tempol's anti-obesity effects
Note: Tempol treatment does not decrease weight gain in Fxr ΔIE mice, indicating intestinal FXR mediates the anti-obesity effects
View evidence from paper
“Further, tempol treatment does not decrease weight gain in Fxr ΔIE mice, suggesting that the intestinal FXR mediates the anti-obesity effects of tempol”