Effect of diet, sex and strain on AG1478-mediated tumor number reduction.

<p>A) <i>Apc^Min</i>^/+ small intestinal and colonic tumor number as a percentage of STD without AG1478 treatment for the B6 inbred and AB6F1 (shaded) strains; and B) AOM (A and AB6F1) colonic tumor number expressed as a percent of STD treatment. The raw values for average number of tumors/mouse are displayed below each graph. STD = standard diet, WD = western diet, “+”  =  AG1478 treatment and “−“  =  no AG1478 treatment. Standard Error of the Mean bars are shown for each treatment. Below bar graphs are estimated effects and significance based on linear mixed models.</p

Comparison of diet compositions.

<p>Comparison of diet compositions.</p

Effect of diet, sex and strain on AG1478-mediated tumor size(mm) reduction.

<p>A) <i>Apc^Min</i>^/+ small intestinal and colonic tumor size as a percentage of STD without AG1478 treatment for the B6 inbred and AB6F1 (shaded) strains; and B) AOM (A and AB6F1) colonic tumor size expressed as a percent of STD treatment. The raw values for average size of tumors/mouse are displayed below each graph. STD = standard diet, WD = western diet, “+”  =  AG1478 treatment and “−“  =  no AG1478 treatment. Standard Error of the Mean bars are shown for each treatment. Below bar graphs are estimated effects and significance based on linear mixed models.</p

Summary of pair-wise observations of AG1478 inhibitor effect on tumor growth.

<p>SD standard diet; WD, western diet; ↓ corrected p<0.05; trend, uncorrected p<0.05 but corrected p>0.05.</p

Western blot analysis of EGFR signal.

<p>Total EGFR and pEGFR in liver protein lysates from A) APC<i>^Min</i>^/+ and B) AOM mice, separately for each strain and sex. STD = standard diet, WD = western diet, “+”  =  AG1478 treatment and “−“  =  no AG1478 treatment. Below bar graphs are estimated effects and significance based on linear mixed models.</p

Supplemental Material for Konganti et al., 2018

Representative outputs from gQTL.<div><br></div><div>Alias names for Collaborative Cross Lines.<br></div><div><br></div><div>Data for TCE levels and Acox1 expression in liver from Collaborative Cross mice.<br></div

Tissue Level Diet and Sex-by-Diet Interactions Reveal Unique Metabolite and Clustering Profiles Using Untargeted Liquid Chromatography–Mass Spectrometry on Adipose, Skeletal Muscle, and Liver Tissue in C57BL6/J Mice

Dietary intervention is commonly used for weight loss or to improve health, as diet-induced obesity increases the risk of developing type 2 diabetes, hypertension, cardiovascular disease, stroke, osteoarthritis, and certain cancers. Various dietary patterns are associated with effects on health, yet little is known about the effects of diet at the tissue level. Using untargeted metabolomics, this study aimed to identify changes in water-soluble metabolites in C57BL/6J males and females fed one of five diets (Japanese, ketogenic, Mediterranean, American, and standard mouse chow) for 7 months. Metabolite abundance was examined in liver, skeletal muscle, and adipose tissue for sex, diet, and sex-by-diet interaction. Analysis of variance (ANOVA) suggests that liver tissue has the most metabolic plasticity under dietary changes compared with adipose and skeletal muscle. The ketogenic diet was distinguishable from other diets for both males and females according to partial least-squares discriminant analysis. Pathway analysis revealed that the majority of pathways affected play an important role in amino acid metabolism in liver tissue. Not surprisingly, amino acid profiles were affected by dietary patterns in skeletal muscle. Few metabolites were significantly altered in adipose tissue relative to skeletal muscle and liver tissue, indicating that it was largely stable, regardless of diet alterations. The results of this study revealed that the ketogenic diet had the largest effect on physiology, particularly for females. Furthermore, metabolomics analysis revealed that diet affects metabolites in a tissue-specific manner and that liver was most sensitive to dietary changes

Supplemental Material for Konganti et al., 2018

File S1 - S5, Figure S1 - S4 and Tables S1-S14

<i>Egfr</i> ablation causes blastocyst implantation site demise.

<p>(<b>A–F</b>) Gross morphology of pregnant uteri. (<b>A–C</b>) <i>Egfr^f/f</i> and (<b>D–F</b>) <i>Egfr^d/d</i> females were mated with wild-type males. The morning observance of a vaginal plug was considered day 0.5 of pregnancy. Pregnancy was assessed at (<b>A,D</b>) d5.5, (<b>B,E</b>) d6.5 and (<b>C,F</b>) d9.5. Scale bars: 1 cm. (<b>G</b>) Average number of implantation sites observed. (<b>H</b>) Average lateral diameter of implantation sites. Numbers represent average +/− the SEM. **-<i>p</i><0.01; ***-<i>p</i><0.001.</p

<i>Egfr</i> is effectively ablated in the murine uterus.

<p>Successful generation of an <i>Egfr</i> conditional knockout (<i>Egfr^d/d</i>) using the <i>Pgr^Cre</i> mouse model as determined by (<b>A</b>) qPCR; average +/− SEM. ***-p<0.001, (<b>B</b>) western blot and (<b>C</b>) immunofluorescence. Scale bars 50 µm.</p