Sarcopenic obesity: molecular clues to a better understanding of its pathogenesis?

Abstract

An age-dependent decline in skeletal muscle mass, strength, and endurance during the aging process is a physiological development, but several factors may exacerbate this process, leading to the threatening state of sarcopenia, frailty, and eventually higher mortality rates. Obesity appears to be such a promoting factor and has been linked in several studies to sarcopenia. The reason for this causal association remains poorly understood. Notwithstanding the fact that a higher body mass might simply lead to diminished physical activity and therefore contribute to a decline in skeletal muscle, several molecular mechanisms have been hypothesized. There could be an obesity derived intracellular lipotoxicity (i.e., elevated intramuscular levels of lipids and their derivatives), which induces apoptosis by means of an elevated oxidative stress. Paracrine mechanisms and inflammatory cytokines, such as CRP and IL-6 could be confounders of the actual underlying pathological mechanism. Due to a cross-talk of the hypothalamo-pituitary axis with nutritional status, obese subjects are more in a catabolic state of metabolism, with a higher susceptibility to muscle wasting under energy restriction. Obesity induces insulin resistance in the skeletal muscle, which consequently leads to perturbed metabolism, and misrouted signaling in the muscle cells. In obesity, muscle progenitor cells could differentiate to an adipocyte-like phenotype as a result of paracrine signals from (adipo)cytokines leading to a reduced muscular renewal capacity. The present review outlines current knowledge concerning possible pathways, which might be involved in the molecular pathogenesis of sarcopenic obesity.

Skeletal muscle mass and quality: evolution of modern measurement concepts in the context of sarcopenia

“…Our report highlights aspects of evaluating these features of skeletal muscle and expands on earlier methodological (17) and historical (2) reviews. While the main phenotypic feature of sarcopenia is loss of lean tissue, notably skeletal muscle, there is growing recognition that sarcopenia can co-exist in the presence of obesity (18) . A skeletal muscle compartment reduced in mass may thus be masked by the presence of excess fat.…”

Association between sarcopenic obesity and cardiovascular risk: where are we?

“…The increase of AT, especially visceral fat, as well as the excess of free fatty acids may induce chronic inflammation by increased secretion of pro-inflammatory cytokines such as TNF-α and interleukin-6 (15,22). The inflammatory process, in turn, not only causes degradation of MM but also promotes insulin resistance (15) that contributes to the changes in the morphology, size and muscle function, leading to the onset and progression of sarcoepnia (22,32). The skeletal muscle is an important tissue to capture glycose and its decrease may promote insulin resistance and its consequences (31,33,34).…”

“…Inflammation also plays a central role in the pathogenesis of insulin resistance and its presence in both changes in BC: obesity and sarcopenia (38,39). In obesity, the accumulation of intramyocellular lipids results in a bioactive lipid intermediates and lipids peroxides that activate the inflammatory cascade (32,40). Furthermore, similar to the AT, muscle tissue has recently been considered an endocrine organ secreting hormones that modulate systemic metabolism.…”

“…Analogs adipokines, myokines are responsible for inhibiting and preventing inflammation and insulin resistance. In individuals with SO the relative scarcity of myokines comparedto adipokines increase the risk of CVD and CMD (32,40). A new adipokine, A-FABP (adipocyte fatty acid-binding protein), has been described as a link between obesity, inflammatoty process and insulin resistance and may be involved in the pathogenesis of SO (12).…”

“…Besides the inflammatory process and insulin resistance, leptin is highlighted in the physiopathology of SO. It is secreted by adipocytes and has physiologic and physiopathologic actions in several organs, including skeletal muscle where it acts stimulating lipolysis and insulin sensitivity (3,32). The leptin receptors have been shown to be negatively regulated by leptin itself and by insulin resistance.…”