Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity
- 1McCaig Institute for Bone and Joint Health, University of Calgary, Canada
- 2Human Performance Laboratory, University of Calgary, Canada
- 3Biomedical Engineering Graduate Group, University of Calgary, Canada
- 4Department of Biochemistry and Molecular Biology, University of Calgary, Canada
- 5Coordenação de Aperfeicoamento de Pessoal de Nível Superior, Brazil
- 6Department of Surgery and Department of Physiology and Pharmacology, University of Calgary, Canada
- 7Department of Orthopaedic Surgery, School of Kinesiology, and Department of Biomedical Engineering, University of Michigan, United States
- 8The Centre for Hip Health & Mobility, University of British Columbia, Canada
- 9Bone & Joint Strategic Clinical Network, Alberta Health Services, Canada
Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK damage. Muscle mass is a key predictor of longevity in older adults, and obesity-induced sarcopenia is a significant risk factor for adverse health outcomes. Muscle is highly plastic, undergoes regular remodeling, and is responsible for the majority of total body glucose utilization, which when impaired leads to insulin resistance. Furthermore, impaired muscle integrity, defined as persistent muscle loss, intramuscular lipid accumulation, or connective tissue deposition, is a hallmark of metabolic dysfunction. In fact, many common inflammatory pathways have been implicated in the pathogenesis of the interrelated tissues of the musculoskeletal system (e.g., tendinopathy, osteoporosis, and osteoarthritis). Despite these similarities, these diseases are rarely evaluated in a comprehensive manner. The aim of this review is to summarize the common pathways that lead to musculoskeletal damage and disease that result from and contribute to MetS. We propose the overarching hypothesis that there is a central role for muscle damage with chronic exposure to an obesity-inducing diet. The inflammatory consequence of diet and muscle dysregulation can result in altered tissue repair and an imbalance toward negative adaptation, resulting in regulatory failure and other musculoskeletal tissue damage. The commonalities support the conclusion that musculoskeletal pathology with MetS should be evaluated in a comprehensive and integrated manner to understand risk for other MSK-related conditions. Implications for conservative management strategies.
Keywords: Joint Diseases, Muscle, Bone, Tendon, NFkB, MAPK
Received: 30 Oct 2017;
Accepted: 05 Feb 2018.
Edited by:Alexandrina F. Mendes, University of Coimbra, Portugal
Reviewed by:Oreste Gualillo, Servicio Gallego de Salud, Spain
Francis Berenbaum, Université Pierre et Marie Curie, France
Tom Appleton, University of Western Ontario, Canada
Copyright: © 2018 Collins, Herzog, MacDonald, Reimer, Rios, Smith, Zernicke and Hart. 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 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.
* Correspondence: Dr. David A. Hart, University of Calgary, McCaig Institute for Bone and Joint Health, 3330 Hospital Drive NW, Calgary, Calgary, T2N4N1, Alberta, Canada, firstname.lastname@example.org