Browsing by Author "Kaur, Amritpal"

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    Loss of Interleukin (IL)-10 Is Associated With Increased Vascular Inflammation and Sex-Differences in Metabolic Outcomes of Normal Diet-Fed Mice
    (Elsevier, 2021) Alake, Sanmi; Ojo, Babajide; Kaur, Amritpal; Hermann, Evan; Ice, John; Chowanadisai, Winyoo; Lin, Dingbo; Smith, Brenda; Lucas, Edralin; Obstetrics and Gynecology, School of Medicine
    Objectives: The anti-inflammatory cytokine, IL-10, plays an important role in reducing the risk of many inflammatory diseases. This study investigated the time and sex effects of IL-10 gene deletion on metabolic risk factors that contribute to the development of cardiovascular disease. Methods: Six-wk-old male and female B6.129P2-Il10tm1Cgn/J (IL-10–/–) and C57BL/6 (WT) mice (n = 12–16/group) were randomly assigned to 12- or 24-wk time points and were fed growth (AIN-93G) diet up to 3 m of age and then maintenance diet (AIN-93M) for the remainder of the study. Monthly fasting glucose was assessed as well as intraperitoneal glucose tolerance test (ipGTT), body composition, and serum metabolic parameters at each study end point. Cardiac and vascular adhesion molecules, macrophage marker F4/80, and sterol metabolism genes were assessed using qPCR. Data were analyzed using t-test and 2-way ANOVA with strain and gender as factors, and α = 0.05. Results: IL-10 deletion resulted in weight loss (p < 0.05) coinciding with reduced fat mass and % fat (P < 0.05) in both sexes of IL-10–/–. Loss of IL-10 had no effect on fasting glucose at any time point in either sex; however, a delayed response to glucose challenge and increased AUC with the ipGTT (P < 0.05) occurred in male IL-10–/– vs WT mice. No strain effect was observed on serum lipids at 12 wks, but cholesterol and high-density lipoprotein (HDL)-C were reduced (P < 0.05) in IL-10–/– vs WT mice at 24 wks. Only male IL-10–/– mice exhibited elevated (P < 0.05) non-HDL cholesterol and tended (P = 0.072) to have elevated triglycerides vs WT mice at 24 wks. In conjunction with serum lipid changes, male IL-10–/– mice increased (P < 0.05) hepatic transcription of β-hydroxy β-methylglutaryl-CoA (HMG-CoA), whereas HMGCoA transcript tended to be repressed (≥ –53.5%; P = 0.08) in female IL-10–/– vs WT mice. At 12 and 24 wks, IL-10–/– exhibited increased (P < 0.05) circulating c-reactive protein and aortic and cardiac gene expression of VCAM-1, ICAM-1, and iNOS. The only increase in the F4/80 macrophage marker occurred in male IL-10–/– mice vs WT at 24 wks. Conclusions: Loss of IL-10 was associated with different metabolic responses in male and female mice and could be detrimental to cholesterol-mediated metabolic processes in female mice on a control diet.
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    Montmorency Tart Cherry Supplementation Has Modest Effects on the Gut Microbiome and Markers of Gut Integrity and Insulin Resistance in Mice Fed Western Diet
    (Elsevier, 2021) Kaur, Amritpal; Ojo, Babajide; Wong, Siau Yen; Alake, Sanmi; Davila-El Rassi, Guadalupe; Pastor, Madison; Lin, Dingbo; Smith, Brenda; Lucas, Edralin; Obstetrics and Gynecology, School of Medicine
    Objectives: This study investigated the dose-dependent effects of freeze-dried Montmorency tart cherry (TC) supplementation on gut health and metabolic parameters in mice fed a western diet (WD). Methods: Six-week-old male C57BL/6 mice were randomly assigned to dietary treatment groups in a 2 × 3 factorial design with diet (control [AIN-93M] or WD, 45% fat kcal and 26% sucrose kcal) and TC (0, 5, 10% wt/wt) as factors for 12 wks. At the end of dietary treatment, body composition was assessed by dual energy xray absorptiometry, and tissues were collected to evaluate metabolic parameters and markers of gut health. Cecal content was used for bacterial and short chain fatty acid analyses (SCFAs). Results: TC at the 10% dose significantly increased the abundance of the beneficial bacterial phylum, Actinobacteria, relative to the unsupplemented groups (P = 0.018 and 0.010 vs control and WD, respectively). Relative cecal weight (P = 0.007) and SCFAs were significantly increased (P < 0.05) with TC supplementation (∼20% and 2-fold for relative cecal weight and SCFAs, respectively). Histological evaluation revealed reduced ileal villi height (P = 0.0348), width (P = 0.0042) and area (P = 0.0132) with WD, and TC did not alter this response. Overall, the expression of genes related to gut health (i.e barrier integrity marker, mucus layer formation, and inflammatory marker), were unaffected by both WD and TC supplementation. Body weight (P = 0.0012), fat mass (P = 0.007), fasting blood glucose (P = 0.001), serum total cholesterol (P < 0.0001), triglyceride (P = 0.002), leptin (P = 0.0011), plasminogen activator inhibitor 1 (P = 0.0344), and resistin (P = 0.0012) were increased with WD, and TC had no effect on these parameters. Despite modest effects on metabolic parameters, the homeostatic model assessment of insulin resistance, HOMA-IR, a commonly used tool for assessing insulin resistance, was improved by 50% with the 5% TC (P = 0.0003). Conclusions: TC supplementation restored some beneficial bacteria and increased SCFAs altered by WD. However, these changes in the gut did not translate to improvement in metabolic outcomes except for HOMA-IR. The mechanism by which TC improves HOMA-IR needs to be investigated in future studies.
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    Supplemental wheat germ modulates phosphorylation of STAT3 in the gut and NF-κBp65 in the adipose tissue of mice fed a Western diet
    (Elsevier, 2022-12-23) Ojo, Babajide A.; Alake, Sanmi E.; Kaur, Amritpal; Wong, Siau Yen; Keirns, Bryant; Ritchey, Jerry W.; Chowanadisai, Winyoo; Lin, Dingbo; Clarke, Stephen; Smith, Brenda J.; Lucas, Edralin A.; Obstetrics and Gynecology, School of Medicine
    Background: Commensal gut bacteria, including Lactobacillus, can produce metabolites that stimulate the release of gut antimicrobial peptides (AMPs) via the signal transducer and activator of transcription (STAT)3 pathway and prevent obesity-associated leaky gut and chronic inflammation. We have previously reported that wheat germ (WG) selectively increased cecal Lactobacillus in obese mice. Objectives: This study investigated the effects of WG on gut STAT3 activation and AMPs (Reg3γ and Reg3β) as well as the potential of WG to inhibit nuclear Nf-κB-activation and immune cell infiltration in the visceral adipose tissue (VAT) of mice fed a Western diet (i.e., high-fat and sucrose diet [HFS]). Methods: Six-wk-old male C57BL/6 mice were randomly assigned to 4 groups (n = 12/group): control (C, 10% fat and sucrose kcal) or HFS (45% fat and 26% sucrose kcal) diet with or without 10% WG (wt/wt) for 12 wk. Assessments include serum metabolic parameters jejunal AMPs genes, inflammatory markers, and phosphorylation of STAT3 as well as VAT NF-κBp65. Independent and interaction effects of HFS and WG were analyzed with a 2-factor ANOVA. Results: WG significantly improved markers of insulin resistance and upregulated jejunal Il10 and Il22 genes. The HFS + WG group had a 15-fold increase in jejunal pSTAT3 compared with the HFS group. Consequently, WG significantly upregulated jejunal mRNA expression of Reg3γ and Reg3β. The HFS group had a significantly higher VAT NF-κBp65 phosphorylation than the C group, while the HFS + WG group suppressed this to the level of C. Moreover, VAT Il6 and Lbp genes were downregulated in the HFS + WG group compared with HFS. Genes related to macrophage infiltration in the VAT were repressed in the WG-fed mice. Conclusion: These findings show the potential of WG to influence vital regulatory pathways in the gut and adipose tissue which may reduce the chronic inflammatory burden on these tissues that are important targets in obesity and insulin resistance.