Dataset Information

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss.

ABSTRACT:

Introduction

Magnesium (Mg) has a prophylactic potential against the onset of hyperlipidemia. Similar to statin, Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass. The combination of statin with Mg ions (Mg²⁺) may be able to alleviate the high-fat diet (HFD)-induced bone loss and reduce the side-effects of statin. This study aimed to explore the feasibility of combined Mg²⁺ with simvastatin (SIM) for treating HFD-induced bone loss in mice and the involving mechanisms.

Materials and methods

C57BL/6 male mice were fed with a HFD or a normal-fat diet (NFD). Mice were intraperitoneally injected SIM and/or orally received water with additional Mg²⁺ until sacrificed. Enzyme-linked immunosorbent assay was performed to measure cytokines and cholesterol in serum and liver lysates. Bone mineral density (BMD) and microarchitecture were assessed by micro-computed tomography (?CT) in different groups. The adipogenesis in palmitate pre-treated HepG2 cells was performed under various treatments.

Results

?CT analysis showed that the trabecular bone mass was significantly lower in the HFD-fed group than that in NFD-fed group since week 8. The cortical thickness in HFD-fed group had a significant decrease at week 24, as compared with NFD-fed group. The combination of Mg²⁺ and SIM significantly attenuated the trabecular bone loss in HFD-fed mice via arresting the osteoclast formation and bone resorption. Besides, such combination also reduced the hepatocytic synthesis of cholesterol and inhibited matrix metallopeptidase 13 (Mmp13) mRNA expression in pre-osteoclasts.

Conclusions

The combination of Mg²⁺ and SIM shows a synergistic effect on attenuating the HFD-induced bone loss. Our current formulation may be a cost-effective alternative treatment to be indicated for obesity-related bone loss.

SUBMITTER: Dai B

PROVIDER: S-EPMC7889436 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss.

Dai Bingyang B Li Xu X Xu Jiankun J Zhu Yuwei Y Huang Le L Tong Wenxue W Yao Hao H Chow Dick Ho-Kiu DH Qin Ling L

Bioactive materials 20210203 8

<h4>Introduction</h4>Magnesium (Mg) has a prophylactic potential against the onset of hyperlipidemia. Similar to statin, Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass. The combination of statin with Mg ions (Mg<sup>2+</sup>) may be able to alleviate the high-fat diet (HFD)-induced bone loss and reduce the side-effects of statin. This study aimed to explore the feasibility of combined Mg<sup>2+</sup> with ...[more]

PMID: 33665494

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Project description:Mechanical stresses associated with physical activity (PA) have beneficial effects on increasing BMD and improving bone quality. However, a high-fat diet (HFD) and obesity tend to have negative effects on bone, by increasing bone marrow adiposity leading to increased excretion of proinflammatory cytokines, which activate RANKL-induced bone resorption. In the current study, whether short-term increased PA via access to voluntary wheel running during early life has persistent and protective effects on HFD-induced bone resorption was investigated. Sixty 4-week-old male C57BL6/J mice were divided into two groups postweaning: without or with PA (access to voluntary running wheel 7-8 km/day) for 4 weeks. After 4 weeks with or without PA, mice were further subdivided into control diet or HFD groups for 8 weeks, and then all animals were switched back to control diet for an additional 4 weeks. Mice from the HFD groups were significantly heavier and obese; however, after 4 weeks of additional control diet their body weights returned to levels of mice on continuous control diet. Using μ-CT and confirmed by pQCT of tibias and spines ex vivo, it was determined that bone volume and trabecular BMD were significantly increased with PA in control diet animals compared with sedentary animals without access to wheels, and such anabolic effects of PA on bone were sustained after ceasing PA in adult mice. Eight weeks of a HFD deteriorated bone development in mice. Unexpectedly, early-life PA did not prevent persistent effects of HFD on deteriorating bone quality; in fact, it exacerbated a HFD-induced inflammation, osteoclastogenesis, and trabecular bone loss in adult mice. In accordance with these data, signal transduction studies revealed that a HFD-induced Ezh2, DNA methyltransferase 3a, and nuclear factor of activated T-cells 1 expression were amplified in nonadherent hematopoietic cells. In conclusion, short-term increased PA in early life is capable of increasing bone mass; however, it alters the HFD-induced bone marrow hematopoietic cell-differentiation program to exacerbate increased bone resorption if PA is halted. © 2021 Arkansas Children's Nutrition Center. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dataset Information

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss.

Introduction

Materials and methods

Results

Conclusions

Publications

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss.

Similar Datasets

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