Browsing by Author "Alake, Sanmi E."

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    Fructooligosaccharides act on the gut-bone axis to improve bone independent of Tregs and alter osteocytes in young adult C57BL/6 female mice
    (Oxford University Press, 2024-02-21) Islam, Proapa; Ice, John A.; Alake, Sanmi E.; Adedigba, Pelumi; Hatter, Bethany; Robinson, Kara; Clarke, Stephen L.; Ford Versypt, Ashlee N.; Ritchey, Jerry; Lucas, Edralin A.; Smith, Brenda J.; Obstetrics and Gynecology, School of Medicine
    Targeting the gut-bone axis with probiotics and prebiotics is considered as a promising strategy to reduce the risk of osteoporosis. Gut-derived short chain fatty acids (SCFA) mediate the effects of probiotics on bone via Tregs, but it is not known whether prebiotics act through a similar mechanism. We investigated how 2 different prebiotics, tart cherry (TC) and fructooligosaccharide (FOS), affect bone, and whether Tregs are required for this response. Eight-wk-old C57BL/6 female mice were fed with diets supplemented with 10% w/w TC, FOS, or a control diet (Con; AIN-93M) diet, and they received an isotype control or CD25 Ab to suppress Tregs. The FOS diet increased BMC, density, and trabecular bone volume in the vertebra (~40%) and proximal tibia (~30%) compared to the TC and control diets (Con), irrespective of CD25 treatment. Both prebiotics increased (P < .01) fecal SCFAs, but the response was greater with FOS. To determine how FOS affected bone cells, we examined genes involved in osteoblast and osteoclast differentiation and activity as well as genes expressed by osteocytes. The FOS increased the expression of regulators of osteoblast differentiation (bone morphogenetic protein 2 [Bmp2], Wnt family member 10b [Wnt10b] and Osterix [Osx]) and type 1 collagen). Osteoclasts regulators were unaltered. The FOS also increased the expression of genes associated with osteocytes, including (Phex), matrix extracellular phosphoglycoprotein (Mepe), and dentin matrix acidic phosphoprotein 1 (Dmp-1). However, Sost, the gene that encodes for sclerostin was also increased by FOS as the number and density of osteocytes increased. These findings demonstrate that FOS has a greater effect on the bone mass and structure in young adult female mice than TC and that its influence on osteoblasts and osteocytes is not dependent on Tregs.
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    Reduced estrogen signaling contributes to bone loss and cardiac dysfunction in interleukin‐10 knockout mice
    (Wiley, 2024) Alake, Sanmi E.; Ice, John; Robinson, Kara; Price, Payton; Hatter, Bethany; Wozniak, Karen; Lin, Dingbo; Chowanadisai, Winyoo; Smith, Brenda J.; Lucas, Edralin A.; Obstetrics and Gynecology, School of Medicine
    Characterization of the interleukin (IL)-10 knockout (KO) mouse with chronic gut inflammation, cardiovascular dysfunction, and bone loss suggests a critical role for this cytokine in interorgan communication within the gut, bone, and cardiovascular axis. We sought to understand the role of IL-10 in the cross-talk between these systems. Six-week-old IL-10 KO mice and their wild type (WT) counterparts were maintained on a standard rodent diet for 3 or 6 months. Gene expression of proinflammatory markers and Fgf23, serum 17β-estradiol (E2), and cardiac protein expression were assessed. Ileal Il17a and Tnf mRNA increased while Il6 mRNA increased in the bone and heart by at least 2-fold in IL-10 KO mice. Bone Dmp1 and Phex mRNA were repressed at 6 months in IL-10 KO mice, resulting in increased Fgf23 mRNA (~4-fold) that contributed to increased fibrosis. In the IL-10 KO mice, gut bacterial β-glucuronidase activity and ovarian Cyp19a1 mRNA were lower (p < 0.05), consistent with reduced serum E2 and reduced cardiac pNOS3 (Ser1119 ) in these mice. Treatment of ileal lymphocytes with E2 reduced gut inflammation in WT but not IL-10 KO mice. In conclusion, our data suggest that diminished estrogen and defective bone mineralization increased FGF23 which contributed to cardiac fibrosis in the IL-10 KO mouse.
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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.