Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis |
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| Institution: | 1. School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia;2. Department of Medicine and Australian Institute for Musculoskeletal Science, Melbourne Medical School—Western Campus, The University of Melbourne, St Albans, Victoria, Australia;3. School of Public Health, University of Sydney, New South Wales, Sydney, Australia;4. Centre for Education and Research on Ageing, Concord Hospital, University of Sydney, New South Wales, Sydney, Australia;5. The ARC Centre of Excellence in Population Ageing Research, University of Sydney, New South Wales, Sydney, Australia;6. ANZAC Research Institute & Charles Perkins Centre, University of Sydney, New South Wales, Sydney, Australia;7. Department of Andrology, Concord Hospital, ANZAC Research Institute, University of Sydney, New South Wales, Sydney, Australia;8. Bone Research Program, ANZAC Research Institute, Dept of Endocrinology & Metabolism, Concord Hospital, The University of Sydney, New South Wales, Sydney, Australia;9. School of Life and Environmental Sciences, Charles Perkins Centre, University of Sydney, New South Wales, Sydney, Australia;1. Section of General Internal Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA;2. Geisel School of Medicine at Dartmouth and The Dartmouth Institute for Health Policy & Clinical Practice, Lebanon, NH 03756, USA;3. Dartmouth Centers for Health and Aging, Dartmouth College, Lebanon, NH 03756, USA;4. Health Promotion Research Center at Dartmouth, Lebanon, NH 03756, USA;5. Dartmouth Weight & Wellness Center, Lebanon, NH 03756, USA;6. Division of Cardiovascular Disease, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA |
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| Abstract: | Sarcopenia, an age-associated decline in skeletal muscle mass coupled with functional deterioration, may be exacerbated by obesity leading to higher disability, frailty, morbidity and mortality rates. In the combination of sarcopenia and obesity, the state called sarcopenic obesity (SOB), some key age- and obesity-mediated factors and pathways may aggravate sarcopenia. This review will analyze the mechanisms underlying the pathogenesis of SOB. In obese adipose tissue (AT), adipocytes undergo hypertrophy, hyperplasia and activation resulted in accumulation of pro-inflammatory macrophages and other immune cells as well as dysregulated production of various adipokines that together with senescent cells and the immune cell-released cytokines and chemokines create a local pro-inflammatory status. In addition, obese AT is characterized by excessive production and disturbed capacity to store lipids, which accumulate ectopically in skeletal muscle. These intramuscular lipids and their derivatives induce mitochondrial dysfunction characterized by impaired β-oxidation capacity and increased reactive oxygen species formation providing lipotoxic environment and insulin resistance as well as enhanced secretion of some pro-inflammatory myokines capable of inducing muscle dysfunction by auto/paracrine manner. In turn, by endocrine manner, these myokines may exacerbate AT inflammation and also support chronic low grade systemic inflammation (inflammaging), overall establishing a detrimental vicious circle maintaining AT and skeletal muscle inflammation, thus triggering and supporting SOB development. Under these circumstances, we believe that AT inflammation dominates over skeletal muscle inflammation. Thus, in essence, it redirects the vector of processes from “sarcopenia → obesity” to “obesity → sarcopenia”. We therefore propose that this condition be defined as “obese sarcopenia”, to reflect the direction of the pathological pathway. |
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| Keywords: | Age Obesity Sarcopenia Sarcopenic obesity Inflammation Adipose tissue Skeletal muscle |
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