High-fat diet-induced osteoporosis in mice under hypoxic conditions

Abstract In the context of global aging, osteoporosis has emerged as a significant public health concern, with a relatively high prevalence observed in plateau regions. This study aimed to investigate the effects and underlying mechanisms of high-fat diet (HFD) and hypoxic conditions on bone metabol...

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Main Authors: Yajun Qiao, Huimin Zheng, Ruiying Cheng, Juan Guo, Li Ji, Zhibin Liu, Lixin Wei, Hongtao Bi, Zhongshu Shan
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Musculoskeletal Disorders
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Online Access:https://doi.org/10.1186/s12891-025-08725-6
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author Yajun Qiao
Huimin Zheng
Ruiying Cheng
Juan Guo
Li Ji
Zhibin Liu
Lixin Wei
Hongtao Bi
Zhongshu Shan
author_facet Yajun Qiao
Huimin Zheng
Ruiying Cheng
Juan Guo
Li Ji
Zhibin Liu
Lixin Wei
Hongtao Bi
Zhongshu Shan
author_sort Yajun Qiao
collection DOAJ
description Abstract In the context of global aging, osteoporosis has emerged as a significant public health concern, with a relatively high prevalence observed in plateau regions. This study aimed to investigate the effects and underlying mechanisms of high-fat diet (HFD) and hypoxic conditions on bone metabolism in mice. The mice were subjected to different dietary regimens (a HFD versus a normal diet) and placed in a hypoxic environment. This study explored relevant mechanisms through comprehensive assessments, including body and bone morphological indices, pathological examinations, biochemical analyses, evaluation of gut microbiota diversity, and metabolomics approaches. The results indicated that, compared with those in the control group, the body weight, Lee’s index, body mass index (BMI), and body fat percentage of the HFD-fed group were significantly greater. Additionally, the femoral microstructure was compromised, bone metabolic markers were disrupted, inflammatory responses were heightened, gut microbiota diversity was altered, and specific intestinal metabolites such as Anserine were downregulated, whereas L-carnosine was upregulated. Spearman correlation analysis and network visualization elucidated the multifactorial influence mechanism of a HFD on bone metabolism under hypoxic conditions. These factors interconnect to form a complex network that drives osteoporosis development. Notably, L-carnosine occupies a central position within this network, serving as a key hub for interactions among various factors. Under the dual stressors of hypoxia and a HFD, this network becomes imbalanced, leading to bone metabolic disorders and osteoporosis. This study provides insights into the multifactorial mechanisms of osteoporosis induced by a HFD and hypoxia in mice, offering a foundation for subsequent research and preventive strategies for osteoporosis in plateau areas.
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spelling doaj-art-92594e70ddd44d258ea7079bdbb195b42025-08-20T03:53:57ZengBMCBMC Musculoskeletal Disorders1471-24742025-05-0126111810.1186/s12891-025-08725-6High-fat diet-induced osteoporosis in mice under hypoxic conditionsYajun Qiao0Huimin Zheng1Ruiying Cheng2Juan Guo3Li Ji4Zhibin Liu5Lixin Wei6Hongtao Bi7Zhongshu Shan8Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of ScienceQinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of ScienceQinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of ScienceDepartment of Orthopedic Surgery, People’s Hospital of Qinghai ProvinceDepartment of Orthopedic Surgery, People’s Hospital of Qinghai ProvinceDepartment of Orthopedic Surgery, People’s Hospital of Qinghai ProvinceQinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of ScienceQinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of ScienceDepartment of Orthopedic Surgery, People’s Hospital of Qinghai ProvinceAbstract In the context of global aging, osteoporosis has emerged as a significant public health concern, with a relatively high prevalence observed in plateau regions. This study aimed to investigate the effects and underlying mechanisms of high-fat diet (HFD) and hypoxic conditions on bone metabolism in mice. The mice were subjected to different dietary regimens (a HFD versus a normal diet) and placed in a hypoxic environment. This study explored relevant mechanisms through comprehensive assessments, including body and bone morphological indices, pathological examinations, biochemical analyses, evaluation of gut microbiota diversity, and metabolomics approaches. The results indicated that, compared with those in the control group, the body weight, Lee’s index, body mass index (BMI), and body fat percentage of the HFD-fed group were significantly greater. Additionally, the femoral microstructure was compromised, bone metabolic markers were disrupted, inflammatory responses were heightened, gut microbiota diversity was altered, and specific intestinal metabolites such as Anserine were downregulated, whereas L-carnosine was upregulated. Spearman correlation analysis and network visualization elucidated the multifactorial influence mechanism of a HFD on bone metabolism under hypoxic conditions. These factors interconnect to form a complex network that drives osteoporosis development. Notably, L-carnosine occupies a central position within this network, serving as a key hub for interactions among various factors. Under the dual stressors of hypoxia and a HFD, this network becomes imbalanced, leading to bone metabolic disorders and osteoporosis. This study provides insights into the multifactorial mechanisms of osteoporosis induced by a HFD and hypoxia in mice, offering a foundation for subsequent research and preventive strategies for osteoporosis in plateau areas.https://doi.org/10.1186/s12891-025-08725-6HypoxiaHFDBone metabolismGut
spellingShingle Yajun Qiao
Huimin Zheng
Ruiying Cheng
Juan Guo
Li Ji
Zhibin Liu
Lixin Wei
Hongtao Bi
Zhongshu Shan
High-fat diet-induced osteoporosis in mice under hypoxic conditions
BMC Musculoskeletal Disorders
Hypoxia
HFD
Bone metabolism
Gut
title High-fat diet-induced osteoporosis in mice under hypoxic conditions
title_full High-fat diet-induced osteoporosis in mice under hypoxic conditions
title_fullStr High-fat diet-induced osteoporosis in mice under hypoxic conditions
title_full_unstemmed High-fat diet-induced osteoporosis in mice under hypoxic conditions
title_short High-fat diet-induced osteoporosis in mice under hypoxic conditions
title_sort high fat diet induced osteoporosis in mice under hypoxic conditions
topic Hypoxia
HFD
Bone metabolism
Gut
url https://doi.org/10.1186/s12891-025-08725-6
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AT juanguo highfatdietinducedosteoporosisinmiceunderhypoxicconditions
AT liji highfatdietinducedosteoporosisinmiceunderhypoxicconditions
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