scholarly journals Faculty Opinions recommendation of Osteoblastic glucocorticoid signaling exacerbates high-fat-diet- induced bone loss and obesity.

2021 ◽  
Author(s):  
Minghao Zheng
Keyword(s):  
Bone Loss ◽  
High Fat Diet ◽  
High Fat ◽  
Glucocorticoid Signaling

scholarly journals Osteoblastic glucocorticoid signaling exacerbates high-fat-diet- induced bone loss and obesity

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sarah Kim ◽  
Holger Henneicke ◽  
Lauryn L. Cavanagh ◽  
Eugenie Macfarlane ◽  
Lee Joanne Thai ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bone Loss ◽  
Bone Formation ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Metabolic Response ◽  
Whole Body ◽  
Wild Type ◽  
High Fat ◽  
Glucocorticoid Signaling

AbstractChronic high-fat diet (HFD) consumption not only promotes obesity and insulin resistance, but also causes bone loss through mechanisms that are not well understood. Here, we fed wild-type CD-1 mice either chow or a HFD (43% of energy from fat) for 18 weeks; HFD-fed mice exhibited decreased trabecular volume (−28%) and cortical thickness (−14%) compared to chow-fed mice. In HFD-fed mice, bone loss was due to reduced bone formation and mineral apposition, without obvious effects on bone resorption. HFD feeding also increased skeletal expression of sclerostin and caused deterioration of the osteocyte lacunocanalicular network (LCN). In mice fed HFD, skeletal glucocorticoid signaling was activated relative to chow-fed mice, independent of serum corticosterone concentrations. We therefore examined whether skeletal glucocorticoid signaling was necessary for HFD-induced bone loss, using transgenic mice lacking glucocorticoid signaling in osteoblasts and osteocytes (HSD2OB/OCY-tg mice). In HSD2OB/OCY-tg mice, bone formation and mineral apposition rates were not suppressed by HFD, and bone loss was significantly attenuated. Interestingly, in HSD2OB/OCY-tg mice fed HFD, both Wnt signaling (less sclerostin induction, increased β-catenin expression) and glucose uptake were significantly increased, relative to diet- and genotype-matched controls. The osteocyte LCN remained intact in HFD-fed HSD2OB/OCY-tg mice. When fed a HFD, HSD2OB/OCY-tg mice also increased their energy expenditure and were protected against obesity, insulin resistance, and dyslipidemia. Therefore, glucocorticoid signaling in osteoblasts and osteocytes contributes to the suppression of bone formation in HFD-fed mice. Skeletal glucocorticoid signaling is also an important determinant of glucose uptake in bone, which influences the whole-body metabolic response to HFD.

scholarly journals Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction

2011 ◽  
Vol 108 (6) ◽  
pp. 1025-1033 ◽  
Author(s):  
Sumithra Urs ◽  
Terry Henderson ◽  
Phuong Le ◽  
Clifford J. Rosen ◽  
Lucy Liaw
Keyword(s):  
Adipose Tissue ◽  
Bone Loss ◽  
Bone Mass ◽  
Body Fat ◽  
High Fat Diet ◽  
Conditional Knockout ◽  
Whole Body ◽  
High Fat ◽  
Tissue Specific ◽  
Diet Induced Obesity

We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

High‐Fat Diet‐Induced Metabolic Syndrome Increases Ligature‐Induced Alveolar Bone Loss in Mice

Oral Diseases ◽  
2021 ◽  
Author(s):  
Zhongyang Lu ◽  
Yanchun Li ◽  
Hong Yu ◽  
Maria F. Lopes‐Virella ◽  
Yan Huang
Keyword(s):  
Metabolic Syndrome ◽  
Bone Loss ◽  
High Fat Diet ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
High Fat

scholarly journals Free Fatty Acid Receptor 4 (GPR120) Stimulates Bone Formation and Suppresses Bone Resorption in the Presence of Elevated n-3 Fatty Acid Levels

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2621-2635 ◽  
Author(s):  
Seong Hee Ahn ◽  
Sook-Young Park ◽  
Ji-Eun Baek ◽  
Su-Youn Lee ◽  
Wook-Young Baek ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Free Fatty Acid Receptor

Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors and that it was activated by docosahexaenoic acid. FFA4 knockout (Ffar4−/−) and wild-type mice exhibited similar bone masses when fed a normal diet. Because fat-1 transgenic (fat-1Tg+) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4−/− and fat-1Tg+ mice over two generations to generate four genotypes of mice littermates: Ffar4+/+;fat-1Tg−, Ffar4+/+;fat-1Tg+, Ffar4−/−;fat-1Tg−, and Ffar4−/−;fat-1Tg+. Female and male littermates were included in ovariectomy- and high-fat diet-induced bone loss models, respectively. Female fat-1Tg+ mice decreased bone loss after ovariectomy both by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In a high-fat diet-fed model, male fat-1Tg+ mice had higher bone mass resulting from stimulated bone formation and reduced bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In vitro studies supported the role of FFA4 as n-3 FA receptor in bone metabolism. In conclusion, FFA4 is a dual-acting factor that increases osteoblastic bone formation and decreases osteoclastic bone resorption, suggesting that it may be an ideal target for modulating metabolic bone diseases.

scholarly journals Effect of Vitamin E Isoforms on Bone Metabolism in C57BL/6 J Mice Fed a High Fat Diet

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1795-1795
Author(s):  
Chen Du ◽  
Gina Tran ◽  
Victorine Imrhan ◽  
Chandan Prasad ◽  
Parakat Vijayagopal ◽  
...  
Keyword(s):  
Vitamin E ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Bone Mineral ◽  
High Fat Diet ◽  
Alpha Tocopherol ◽  
Type I ◽  
High Fat ◽  
Mineral Density ◽  
Gamma Tocopherol

Abstract Objectives The purpose of this study was to compare the effects of alpha tocopherol, gamma tocopherol, and the combination of alpha and gamma tocopherols on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism in C57BL/6 J mice fed a high-fat diet. Methods A total of 75 male C57BL/6 mice were randomized to either a low fat diet (LFD) with 6% fat, a high fat diet (HFD) with 20% fat, HFD supplemented with alpha tocopherol (AT), gamma tocopherol (GT), or the combination of AT and GT. LFD and HFD were provided to corresponding groups of mice without vitamin E isoform supplements for 15 weeks to induce bone loss. At the end of the 15 weeks, AT, GT, and a combination of AT and GT were added to 3 of the HFD groups and fed for 10 weeks. LFD group and one of the HFD groups were continued on the same diet for another 10 weeks without additional supplements. All mice were euthanized at the end of the 25 weeks period. Left and right fibula bones were excised, cleaned, and scanned using the Lunar PIXImus dual-energy x-ray absorptiometry (DEXA) densitometer to assess BMD, BMC, lean tissue, and fat tissue content. Serum biomarkers of bone metabolism were evaluated post euthanization. Results HFD resulted in significantly lower fibular BMD and higher tibial bone fat content in comparison to LFD. Animals in the HFD supplemented with GT, but not AT, showed significantly reduced effect of HFD in lowering BMD. Additionally, in the group fed HFD supplemented with GT, a significantly higher concentration of alkaline phosphatase (ALP) and N-terminal propeptide of type I procollagen (PINP) were noted, compared to LFD. This may be indicative of increased bone formation resulting from GT incorporated into the HFD diet. Conclusions The findings of the study suggest that different isoforms of vitamin E affect bone density and bone metabolism differently. Within the different isoforms of vitamin E, gamma tocopherol may have protective effects in bone, especially in the situation of high fat diet induced bone loss. Further examination of the mechanistic action of vitamin E isoforms on skeletal health is warranted. Funding Sources Texas Woman's University.

The effects of palm tocotrienol on metabolic syndrome and bone loss in male rats induced by high-carbohydrate high-fat diet

2018 ◽  
Vol 44 ◽  
pp. 246-254 ◽  
Author(s):  
Sok Kuan Wong ◽  
Kok-Yong Chin ◽  
Farihah Hj Suhaimi ◽  
Fairus Ahmad ◽  
Soelaiman Ima-Nirwana
Keyword(s):  
Metabolic Syndrome ◽  
Bone Loss ◽  
High Fat Diet ◽  
Male Rats ◽  
High Fat ◽  
High Carbohydrate

scholarly journals Paradoxical resistance to high-fat diet-induced obesity and altered macrophage polarization in mineralocorticoid receptor-overexpressing mice

2014 ◽  
Vol 306 (1) ◽  
pp. E75-E90 ◽  
Author(s):  
Emmanuelle Kuhn ◽  
Christine Bourgeois ◽  
Vixra Keo ◽  
Say Viengchareun ◽  
Adeline Muscat ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Mineralocorticoid Receptor ◽  
Body Weight Gain ◽  
Macrophage Polarization ◽  
Metabolic Phenotype ◽  
High Fat ◽  
Glucocorticoid Signaling ◽  
Lower Body Weight

The mineralocorticoid receptor (MR) exerts proadipogenic and antithermogenic effects in vitro, yet its in vivo metabolic impact remains elusive. Wild type (WT) and transgenic (Tg) mice overexpressing human MR were subjected to standard chow (SC) or high-fat diet (HFD) for 16 wk. Tg mice had a lower body weight gain than WT animals and exhibited a relative resistance to HFD-induced obesity. This was associated with a decrease in fat mass, an increased population of smaller adipocytes, and an improved glucose tolerance compared with WT animals. Quantitative RT-PCR studies revealed decreased expression of PPARγ2, a master adipogenic gene, and of glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 1, consistent with an impaired local glucocorticoid signaling in adipose tissues (AT). This paradoxical resistance to HFD-induced obesity was not related to an adipogenesis defect since differentiation capacity of Tg preadipocytes isolated from stroma-vascular fractions was unaltered, suggesting that other nonadipocyte factors might compromise AT development. Although AT macrophage infiltration was not different between genotypes, Tg mice exhibited a distinct macrophage polarization, as revealed by FACS analysis and CD11c/CD206 expression studies. We further demonstrated that Tg macrophage-conditioned medium partially impaired preadipocyte differentiation. Therefore, we propose that modification of M1/M2 polarization of hMR-overexpressing macrophages could account in part for the metabolic phenotype of Tg mice. Collectively, our results provide evidence that MR exerts a pivotal immunometabolic role by controlling adipocyte differentiation processes directly but also indirectly through macrophage polarization regulation. Our findings should be taken into account for the pharmacological treatment of metabolic disorders.

scholarly journals Interleukin-6 Knockout Inhibits Senescence of Bone Mesenchymal Stem Cells in High-Fat Diet-Induced Bone Loss

2021 ◽  
Vol 11 ◽  
Author(s):  
Yujue Li ◽  
Lingyun Lu ◽  
Ying Xie ◽  
Xiang Chen ◽  
Li Tian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
Interleukin 6 ◽  
High Fat Diet ◽  
Cell Senescence ◽  
Low Grade ◽  
High Fat ◽  
Bone Mesenchymal Stem Cells

Obesity, a chronic low-grade inflammatory state, not only promotes bone loss, but also accelerates cell senescence. However, little is known about the mechanisms that link obesity, bone loss, and cell senescence. Interleukin-6 (IL-6), a pivotal inflammatory mediator increased during obesity, is a candidate for promoting cell senescence and an important part of senescence-associated secretory phenotype (SASP). Here, wild type (WT) and (IL-6 KO) mice were fed with high-fat diet (HFD) for 12 weeks. The results showed IL-6 KO mice gain less weight on HFD than WT mice. HFD induced trabecular bone loss, enhanced expansion of bone marrow adipose tissue (BMAT), increased adipogenesis in bone marrow (BM), and reduced the bone formation in WT mice, but it failed to do so in IL-6 KO mice. Furthermore, IL-6 KO inhibited HFD-induced clone formation of bone marrow cells (BMCs), and expression of senescence markers (p53 and p21). IL-6 antibody inhibited the activation of STAT3 and the senescence of bone mesenchymal stem cells (BMSCs) from WT mice in vitro, while rescued IL-6 induced senescence of BMSCs from IL-6 KO mice through the STAT3/p53/p21 pathway. In summary, our data demonstrated that IL-6 KO may maintain the balance between osteogenesis and adipogenesis in BM, and restrain senescence of BMSCs in HFD-induced bone loss.

scholarly journals Magnesium Picolinate Improves Bone Formation by Regulation of RANK/RANKL/OPG and BMP-2/Runx2 Signaling Pathways in High-Fat Fed Rats

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3353
Author(s):  
Emre Sahin ◽  
Cemal Orhan ◽  
Tansel Ansal Balci ◽  
Fusun Erten ◽  
Kazim Sahin
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
High Fat Diet ◽  
Male Rats ◽  
High Fat ◽  
Mineral Density ◽  
Protein Levels ◽  
Prevent Bone Loss ◽  
Osteogenic Protein ◽  
Affect Bone Metabolism

Magnesium (Mg) deficiency may affect bone metabolism by increasing osteoclasts, decreasing osteoblasts, promoting inflammation/oxidative stress, and result in subsequent bone loss. The objective of the present study was to identify the molecular mechanism underlying the bone protective effect of different forms of Mg (inorganic magnesium oxide (MgO) versus organic magnesium picolinate (MgPic) compound) in rats fed with a high-fat diet (HFD). Forty-two Wistar albino male rats were divided into six group (n = 7): (i) control, (ii) MgO, (iii) MgPic, (iv) HFD, (v) HFD + MgO, and (vi) HFD + MgPic. Bone mineral density (BMD) increased in the Mg supplemented groups, especially MgPic, as compared with the HFD group (p < 0.001). As compared with the HFD + MgO group, the HFD + MgPic group had higher bone P (p < 0.05) and Mg levels (p < 0.001). In addition, as compared to MgO, MgPic improved bone formation by increasing the levels of osteogenetic proteins (COL1A1 (p < 0.001), BMP2 (p < 0.001), Runx2 (p < 0.001), OPG (p < 0.05), and OCN (p < 0.001), IGF-1 (p < 0.001)), while prevented bone resorption by reducing the levels of RANK and RANKL (p < 0.001). In conclusion, the present data showed that the MgPic could increase osteogenic protein levels in bone more effectively than MgO, prevent bone loss, and contribute to bone formation in HFD rats.

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