Browsing by Author "Hatter, Bethany"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Dietary Supplementation With Montmorency Tart Cherries and Exercise Improves Lean Mass in Older C57BL/6 Mice
    (Elsevier, 2021) Robinson, Kara; Hatter, Bethany; Washburn, Karley; Bothwell, James; Anderson, Kendall; Lin, Dingbo; Lucas, Edralin; Smith, Brenda; Obstetrics and Gynecology, School of Medicine
    Objectives: Sarcopenia, the progressive loss of muscle mass and strength, accelerates with age. Current recommendations to prevent sarcopenia focus on exercise and protein intake. Tart cherry (TC) has shown beneficial effects on muscle recovery following exercise. In this study, we investigated the effects of TC alone and in combination with exercise on lean mass, mitochondrial biogenesis, and oxidative stress in young compared to older mice. Methods: In two cohorts (6 & 52 wk-old), female C57BL/6 mice were randomly assigned to 4 groups in a 2 × 2 factorial design with diet (AIN-93 control or TC supplemented at 10% w/w) and exercise as factors. Exercise consisted of treadmill running for 30 min, 5 d/wk, at 12 m/min and a 5° incline. Food intake was recorded daily and body weights weekly. After 8 wks, body composition was assessed using dual-energy x-ray absorptiometry. The gastrocnemius muscle was collected for protein analysis. Western blotting techniques were used to probe for superoxide dismutase 2 (SOD2) and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1a), indicators of oxidative stress and mitochondrial biogenesis. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control. Data were analyzed using 2-way ANOVA with α = 0.05. Results: In young mice, TC had no effect on body weight and % lean mass, but led to decreased (P < 0.05) % fat mass compared to controls. Exercise decreased (P < 0.05) body weight and % fat, and tended to increase (P = 0.069) % lean mass. In contrast, TC and exercise independently decreased body weight and % fat, and increased % lean mass in older mice compared to controls. The combination of TC and exercise tended to have a synergistic effect on % lean mass (P = 0.056). Preliminary results show that TC significantly up-regulated SOD2 protein expression in young mice, but no effect was observed with exercise or combined treatments. PGC1α expression tended to be suppressed (P = 0.064) in young animals fed TC. To date, we have been unable to detect changes in SOD2 and PGC1α in older mice. Conclusions: TC had a protective effect on lean tissue in older mice, preliminary analyses revealed no alterations in oxidative stress or mitochondrial biogenesis. Further investigation is warranted to understand the benefits of TC on lean muscle mass in older mice.
  • Thumbnail Image
    Item
    Differential Effects of the Polyphenols and Carbohydrates in Dried Plum Account for the Fruit’s Benefits on Bone Health in Estrogen Deficiency
    (Elsevier, 2021) Hatter, Bethany; Washburn, Karley; Graef-Downard, Jennifer; Crokett, Erica; King, Jarrod; Cichewicz, Robert; Lucas, Edralin; Smith, Brenda; Obstetrics and Gynecology, School of Medicine
    Objectives: This study investigated the effects of dried plum’s (DP) polyphenols (PP) and carbohydrates (CHO) on bone mass, microarchitecture, and biomarkers of metabolism over time in an osteopenic model of estrogen deficiency. Methods: A 2 × 2 factorial (factors CHO & PP) embedded within a randomized block design was used with 3-m old C57BL/6 female mice, sham-operated (Sham = 2 groups) and fed AIN-93M control diet (Con) or ovariectomized (OVX = 10 groups) and fed Con or Con diet supplemented with DP (25% w/w), a comparable dose of crude PP extract (CPE), fractionated CHO or PP extract for 5 or 10 wks. At each end-point, dual-energy x-ray absorptiometry scans were performed and bone microarchitecture was assessed at the femur and lumbar vertebra using micro-computed x-ray tomography. Serum biomarkers of osteoblast activity, procollagen type 1 N-terminal propeptide (P1NP), and osteoclast activity, tartrate-resistant acid phosphate (TRAP) were assayed using EIAs. Data was analyzed using SAS with effects of DP and CPE examined using 1-way ANOVA and effects of PP and CHO examined using a 2-way ANOVA. Results: At 5 and 10-wks, mice on the DP and CPE diets had higher (P < 0.05) whole body bone mineral density (BMD), content (BMC), trabecular bone volume (BV/TV) and number (TbN) in the vertebrae and femur compared to the OVX-Con. By 10 wks, improvements in trabecular bone with DP and CPE were greater (P < 0.05) than Sham. Only the CPE significantly improved cortical thickness, a response observed at only 5 wks. DP and CPE had no effect on P1NP, but suppressed OVX-induced increase in TRAP at 5 and 10 wks. PP and CHO increased (P < 0.05) whole body BMD and BMC. CHO significantly improved trabecular BV/TV, TbN, separation, connectivity density, and structure model index at both time points. A similar response occurred in vertebral trabecular bone. In contrast, cortical thickness was increased (P < 0.05) with CHO at 5 wks, but by 10 wks PP alone and in combination with CHO accounted for improved cortical area, thickness and porosity. CHO suppressed TRAP at both time points, but P1NP only at 5 wks. PP did not alter P1NP and only when combined with CHO suppressed TRAP at 5 wks. Conclusions: In the OVX model, both the CHO and PP of DP positively affect BMD, with the CHO fraction enhancing trabecular bone and the PP fraction improving cortical bone.
  • Thumbnail Image
    Item
    Dried Plum’s Polyphenolic Compounds and Carbohydrates Contribute to Its Osteoprotective Effects and Exhibit Prebiotic Activity in Estrogen Deficient C57BL/6 Mice
    (MDPI, 2022-04-19) Smith, Brenda J.; Hatter, Bethany; Washburn, Karley; Graef-Downard, Jennifer; Ojo, Babajide A.; El-Rassi, Guadalupe Davila; Cichewicz, Robert H.; Payton, Mark; Lucas, Edralin A.; Obstetrics and Gynecology, School of Medicine
    Evidence of dried plum’s benefits on bone continues to emerge. This study investigated the contribution of the fruit’s polyphenol (PP) and carbohydrate (CHO) components on a bone model of postmenopausal osteoporosis to explore their prebiotic activity. Osteopenic ovariectomized mice were fed diets supplemented with dried plum, a crude extract of dried plum’s polyphenolic compounds, or the PP or CHO fraction of the crude extract. The effects of treatments on the bone phenotype were assessed at 5 and 10 weeks as well as the prebiotic activity of the different components of dried plum. Both the CHO and PP fractions of the extract contributed to the effects on bone with the CHO suppressing bone formation and resorption, and the PP temporally down-regulating formation. The PP and CHO components also altered the gut microbiota and cecal short chain fatty acids. These findings demonstrate that the CHO as well as the PP components of dried plum have potential prebiotic activity, but they have differential roles in mediating the alterations in bone formation and resorption that protect bone in estrogen deficiency.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Understanding How Sex Influences the Impact of IL-10 on Bone Microarchitecture and Bone Metabolism Over Time
    (Elsevier, 2021) Price, Payton; Perez, Leo; Hatter, Bethany; Robinson, Kara; Islam, Proapa; Alake, Sanmi; Ice, John; Lucas, Edralin; Smith, Brenda; Obstetrics and Gynecology, School of Medicine
    Objectives: Dietary interventions with pre- and probiotics favorably affect the gut-bone axis, mediated in part by the anti-inflammatory cytokine, interleukin (IL)-10. This study sought to understand how IL-10’s impact on bone metabolism and microarchitecture differs with sex and time. Methods: Six-week-old B6.129P2-Il10tm1Cgn/J (KO) and C57BL/6 (WT) mice were assigned in a 2 × 2 × 2 factorial design with strain (WT & KO), sex, and time (3 & 6 m) as factors. Mice were fed AIN-93G diet for 3 m followed by AIN-93 M for the study duration. Dual-energy x-ray absorptiometry was used to assess bone mineral content (BMC) and density (BMD). Micro-computed tomography was used to assess femur and lumbar vertebrae trabecular and cortical bone. Serum procollagen 1 intact N-terminal propeptide (P1NP) and C-terminal telopeptide of type I collagen (CTX-1), bone formation and resorption markers respectively, were assessed by ELISA. Data were analyzed using ANOVA; p < 0.05 was considered significant. Results: Reductions in BMC and BMD (P < 0.05) in KO vs WT and at 3 vs 6 m were observed; a sex effect was found with reductions in BMC in KO females compared to KO males. Femoral trabecular bone volume (BV/TV) was lower (P < 0.05) in KO vs WT, females vs males, and at 6 vs 3 m. Trabecular thickness (TbTh) decreased (P < 0.05) in KO vs WT and increased from 3 to 6 m, while decreases in trabecular number (TbN) were greater (P < 0.05) in KO mice, females, and at 6 m compared to counterparts. Cortical area and thickness were decreased (P < 0.05) in KO vs WT and in females vs males, which was greater at 6 m, while cortical bone porosity was higher in KO vs WT and increased at 6 mo. Vertebral trabecular BV/TV was lower (P < 0.05) in KO vs WT at 3 and 6 m, with KO females showing reduced BV/TV (P < 0.05) from 3 to 6 m. Reduced TbTh and TbN were observed in KO vs WT, and females had increased (P < 0.05) TbTh and trabecular separation and reduced TbN. P1NP showed a time effect (P < 0.05) with reductions in WT females and males at 6 m compared to 3 m KO females (P < 0.05). CTX-1 shows a sex effect (P < 0.05) and a trending strain effect (P = 0.059), with elevated serum CTX-1 in 3 m KO males compared to WT and KO females at 6 m (P < 0.05). Conclusions: While IL-10 plays an important role in maintaining both trabecular and cortical bone, it may have a more protective effect on the cortical bone of female mice over time.