Sarcopenic obesity and endocrinal adaptation with age

Abstract

In normal aging, changes in the body composition occur that result in a shift toward decreased muscle mass and increased fat mass. The loss of muscle mass that occurs with aging is termed sarcopenia and is an important cause of frailty, disability, and loss of independence in older adults. Age-related changes in the body composition as well as the increased prevalence of obesity determine a combination of excess weight and reduced muscle mass or strength, recently defined as sarcopenic obesity. Weight gain increases total/abdominal fat, which, in turn, elicits inflammation and fatty infiltration in muscle. Sarcopenic obesity appears to be linked with the upregulation of TNF-α, interleukin (IL)-6, leptin, and myostatin and the downregulation of adiponectin and IL-15. Multiple combined exercise and mild caloric restriction markedly attenuate the symptoms of sarcopenic obesity. Intriguingly, the inhibition of myostatin induced by gene manipulation or neutralizing antibody ameliorates sarcopenic obesity via increased skeletal muscle mass and improved glucose homeostasis. In this review, we describe the possible influence of endocrinal changes with age on sarcopenic obesity.

Figure 1

Obesity-induced changes in adipokine secretion and the development of insulin resistance in sarcopenic muscle. Expansion of adipose tissue in obesity leads to increased macrophage infiltration and inflammation with enhanced production of proinflammatory cytokines such as TNF-α and IL-6. This is accompanied by a dysregulated secretion of leptin and adiponectin. These adipocyte- and macrophage-derived adipokines elicit a variety of adverse effects on numerous tissues including the hypothalamus, liver, pancreas, and skeletal muscle. On the systemic level, altered adipokine secretion can lead to increased food intake and reduced energy expenditure through actions in the hypothalamus and to decreased muscle insulin sensitivity.