The Role of Crosstalk between Adipose Cells and Myocytes in the Pathogenesis of Sarcopenic Obesity in the Elderly

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Abstract

As a result of aging, body composition changes, with a decline in muscle mass and an increase in adipose tissue (AT), which reallocates from subcutaneous to visceral depots and stores ectopically in the liver, heart and muscles. Furthermore, with aging, muscle and AT, both of which have recognized endocrine activity, become dysfunctional and contribute, in the case of positive energy balance, to the development of sarcopenic obesity (SO). SO is defined as the co-existence of excess adiposity and low muscle mass and function, and its prevalence increases with age. SO is strongly associated with greater morbidity and mortality. The pathogenesis of SO is complex and multifactorial. This review focuses mainly on the role of crosstalk between age-related dysfunctional adipose and muscle cells as one of the mechanisms leading to SO. A better understanding of this mechanisms may be useful for development of prevention strategies and treatments aimed at reducing the occurrence of SO.

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Sarcopenia: revised European consensus on definition and diagnosis

Alfonso Cruz-Jentoft, Gulistan Bahat, Jürgen Bauer … (2018)

Abstract Background in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

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Muscles, exercise and obesity: skeletal muscle as a secretory organ.

Bente K. Pedersen, Mark A. Febbraio (2012)

During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.

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A PGC1α-dependent myokine that drives browning of white fat and thermogenesis

Pontus Boström, Yao-jun Wu, Mark P. Jedrychowski … (2012)

Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional coactivator PGC1α Here we show that PGC1α expression in muscle stimulates an increase in expression of Fndc5, a membrane protein that is cleaved and secreted as a new hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be a protein therapeutic for human metabolic disease and other disorders that are improved with exercise.