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      Fatty infiltration in the musculoskeletal system: pathological mechanisms and clinical implications

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          Abstract

          Fatty infiltration denotes the anomalous accrual of adipocytes in non-adipose tissue, thereby generating toxic substances with the capacity to impede the ordinary physiological functions of various organs. With aging, the musculoskeletal system undergoes pronounced degenerative alterations, prompting heightened scrutiny regarding the contributory role of fatty infiltration in its pathophysiology. Several studies have demonstrated that fatty infiltration affects the normal metabolism of the musculoskeletal system, leading to substantial tissue damage. Nevertheless, a definitive and universally accepted generalization concerning the comprehensive effects of fatty infiltration on the musculoskeletal system remains elusive. As a result, this review summarizes the characteristics of different types of adipose tissue, the pathological mechanisms associated with fatty infiltration in bone, muscle, and the entirety of the musculoskeletal system, examines relevant clinical diseases, and explores potential therapeutic modalities. This review is intended to give researchers a better understanding of fatty infiltration and to contribute new ideas to the prevention and treatment of clinical musculoskeletal diseases.

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          Most cited references159

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          mTOR at the nexus of nutrition, growth, ageing and disease

          Grace Y. Liu, David Sabatini (2020)
          The mTOR pathway integrates a diverse set of environmental cues, such as growth factor signals and nutritional status, to direct eukaryotic cell growth. Over the past two and a half decades, mapping of the mTOR signalling landscape has revealed that mTOR controls biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Given the pathway’s central role in maintaining cellular and physiological homeostasis, dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing. In this Review, we highlight recent advances in our understanding of the complex regulation of the mTOR pathway and discuss its function in the context of physiology, human disease and pharmacological intervention.
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            Mechanisms linking obesity to insulin resistance and type 2 diabetes.

            Steven E. Kahn, Rebecca Hull, Kristina Utzschneider (2006)
            Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells - the cells that release insulin - failure to control blood glucose levels results. Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention.
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              Sarcopenia: revised European consensus on definition and diagnosis

              Alfonso Cruz-Jentoft, Gϋlistan Bahat, Jϋrgen Bauer … (2019)
              doi: 10.1093/ageing/afy169 In the original version of the above paper there was an error in Table 3, which shows the recommended cut-off points for ASM/height2 in women. The cut-off point was given as <6.0 kg/m2, but the correct value is <5.5 kg/m2. This has now been corrected online. The authors wish to apologise for this error.
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                Author and article information

                Contributors
                Yihua Zhu: URI : https://loop.frontiersin.org/people/2694478Role: Role:
                Yue Hu: URI : https://loop.frontiersin.org/people/1425164Role: Role:
                Yalan Pan: Role:
                Muzhe Li: Role:
                Yuanyuan Niu: Role:
                Tianchi Zhang: URI : https://loop.frontiersin.org/people/2215340Role:
                Haitao Sun: Role:
                Shijie Zhou: Role:
                Mengmin Liu: Role:
                Yili Zhang: URI : https://loop.frontiersin.org/people/875497Role:
                Chengjie Wu: URI : https://loop.frontiersin.org/people/2077686Role:
                Yong Ma: Role: Role:
                Yang Guo: URI : https://loop.frontiersin.org/people/1330565Role: Role:
                Lining Wang: URI : https://loop.frontiersin.org/people/1758292Role: Role:
                Journal
                Journal ID (nlm-ta): Front Endocrinol (Lausanne)
                Journal ID (iso-abbrev): Front Endocrinol (Lausanne)
                Journal ID (publisher-id): Front. Endocrinol.
                Title: Frontiers in Endocrinology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-2392
                Publication date (Electronic): 28 June 2024
                Publication date Collection: 2024
                Volume: 15
                Electronic Location Identifier: 1406046
                Affiliations
                [1] 1 Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine , Nanjing, Jiangsu, China
                [2] 2 School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing, Jiangsu, China
                [3] 3 Traditional Chinese Medicine (TCM) Nursing Intervention Laboratory of Chronic Disease Key Laboratory, Nanjing University of Chinese Medicine , Nanjing, Jiangsu, China
                [4] 4 Department of Orthopedic Surgery, Affiliated Huishan Hospital of Xinglin College of Nantong University , Wuxi, Jiangsu, China
                [5] 5 Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng TCM Hospital , Yancheng, Jiangsu, China
                [6] 6 Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine , Wuxi, Jiangsu, China
                [7] 7 Chinese Medicine Centre (International Collaboration between Western Sydney University and Beijing University of Chinese Medicine), Western Sydney University , Sydney, Australia
                Author notes

                Edited by: Zhousheng Xiao, University of Tennessee Health Science Center (UTHSC), United States

                Reviewed by: Elisa Villalobos, Newcastle University, United Kingdom

                Endre Károly Kristóf, University of Debrecen, Hungary

                *Correspondence: Lining Wang, wln@ 123456njucm.edu.cn ; Yang Guo, drguoyang@ 123456njucm.edu.cn

                †These authors have contributed equally to this work and share first authorship

                Article
                DOI: 10.3389/fendo.2024.1406046
                PMC ID: 11241459
                SO-VID: 520fd813-184d-4d18-b149-6df89687c2a0
                Copyright © Copyright © 2024 Zhu, Hu, Pan, Li, Niu, Zhang, Sun, Zhou, Liu, Zhang, Wu, Ma, Guo and Wang
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 27 March 2024
                Date accepted : 10 June 2024
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 160, Pages: 17, Words: 9604
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (82074458,82174411). This research is also sponsored by Natural Science Foundation of Jiangsu Province (BK20221351, BK20220470), Natural Science Foundation of the Jiangsu Higher education Institution of China (22KJB360012), Foundation of Wuxi Municipal Bureau of Science and Technology(Y20212043), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(Integration of Chinese and Western Medicine), and Foundation of Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease (Jiangsu science and education of traditional Chinese medicine [2021] No.4).
                Categories
                Subject: Endocrinology
                Subject: Review
                Custom metadata
                section-in-acceptance Bone Research

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: aging,fatty infiltration,lipotoxicity,musculoskeletal system,adipose tissue
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: aging, fatty infiltration, lipotoxicity, musculoskeletal system, adipose tissue

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