An accumulation of muscle macrophages is accompanied by altered insulin sensitivity after reduced activity and recovery

Abstract

Background Mechanisms underlying physical inactivity‐induced insulin resistance are not well understood. In addition to a role in muscle repair, immune cell populations such as macrophages may regulate insulin sensitivity. Aim The aim of this study was to examine if the dynamic changes in insulin sensitivity during and after recovery from reduced physical activity corresponded to changes in skeletal muscle macrophages. Methods In this prospective clinical study, we collected muscle biopsies from healthy older adults (70 ± 2 years, n = 12) before and during a hyperinsulinaemic‐euglycaemic clamp and this occurred before (PRE) and after 2‐week reduced physical activity (RA), and following 2‐week of recovery (REC). Insulin sensitivity (hyperinsulinaemic‐euglycaemic clamp), skeletal muscle mRNA expression of inflammatory markers, and immunofluorescent quantification of skeletal muscle macrophages, myofibre‐specific satellite cell and capillary content were assessed. Results Insulin sensitivity was decreased following reduced activity and rebounded following recovery above PRE levels. We observed an increase (P < 0.01) in muscle macrophages (CD68+CD206+: 190 [55, 324]; CD11b+CD206+: 117 [28, 205]% change from PRE) and CD68 (2.4 [1.4, 3.4]‐fold) and CCL2 (1.9 [1.3, 2.5]‐fold) mRNA following RA concurrent with increased (P < 0.03) satellite cells (55 [6, 104]%) in slow‐twitch myofibres. Moreover, the distance of satellite cells to the nearest capillary was increased 7.7 (1.7, 13.7) µm in fast‐twitch myofibres at RA (P = 0.007). Changes in macrophages were positively associated with increased insulin sensitivity following RA (R > 0.57, P < 0.05). Conclusion These findings suggested that a dynamic response of skeletal muscle macrophages following acute changes in physical activity in healthy older adults is related to insulin sensitivity.

An altered response in macrophage phenotype following damage in aged human skeletal muscle: implications for skeletal muscle repair

“…Perhaps the advancement of functional measures will need to be developed to provide a more conclusive indicator of specific heterogeneous cell populations. Nonetheless, despite the limitation of using cell surface markers to define the role of macrophage populations, we believe that sufficient evidence exists to validate our interpretation of the markers used in this study (25,(40)(41)(42), with the understanding that studies to improve macrophage identification are ongoing (43).…”

Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic

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Obesity is a risk factor for developing critical condition in COVID‐19 patients: A systematic review and meta‐analysis

“…Another contributor could be the sedentary lifestyle alone or together with insulin resistance that influences the immune response to microbial agents by impaired macrophage differentiation and modulation of proinflammatory cytokine levels giving way to the invasion of infectious pathogens. 10,11 Interestingly, the obesity survival paradox has been described in certain diseases such as community-acquired pneumonia, where despite the increased risk of developing pneumonia, an inverse association could be observed between obesity and mortality. 6 To the contrary, in the 2009 H1N1 pandemic, obesity was identified as an independent risk factor of severe disease, hospitalization and death.…”