Sarcopenia and skeletal muscle dysfunction in patients with NAFLD

It is well known how Non Alcoholic Fatty Liver Disease (NAFLD) prevalence has been progressively increasing in the last decades, and it’s nowadays the most common cause of liver disease in Western countries [1]. Its increased diffusion has been proven even in Asia and South America, where NAFLD showed a prevalence comparable to the one of the Western countries since the early 2000s [2].

Given its strict connection with metabolic syndrome and, therefore, with visceral obesity, type 2 diabetes mellitus and dyslipidemia, it is hard to imagine that a patient with NAFLD could show signs of nutritional deficiencies. Despite this, NAFLD shares with cirrhosis of other etiologies the possible presence of muscular structural alterations of various degrees. Indeed, it is now clear how the altered relationship between adipose tissue and skeletal muscles is fundamental in the natural course of NAFLD.

In fact, excess of adipose tissue with increased triglyceride storage is responsible of increased lipotoxicity, inflammation and altered neuroendocrine function, due to the accumulation of toxic lipid molecules, such as ceramides, diacylglycerol and long-chain acyl CoA. This leads to an altered secretion of adipokines, with an increased resistence to the effects of leptin, and the consequent worsening of insulin resistance, upregulation of pro-inflammatory cytokines and increased liver fibrogenesis [3-4]. When the excess of lipids is too much even for adipocytes, it accumulates in the liver and in skeletal muscles. Pathological intramyocellular lipid storage results in mitochondrial dysfunction, myocellular apoptosis and an altered secretion of myokines. As a result, a disregulated interaction between muscles, adipose tissue and the liver establishes, worsening the severity and the effects of insulin-resistence [5].

Lipid excess and the aforementioned consequent accumulation in skeletal muscle is the responsible for a process called “myosteatosis”, which is characteristically associated with liver steatosis and it is associated with reduced muscle function and strength, muscle atrophy and physical disabilities [6-7]. The consequence of myosteatosis is the reduction in muscular mass, that is defined as sarcopenia. From a clinical point of view, however, these changings often go unnoticed in these patients, considering that this reduction is more often “qualitative” than “quantitative”, with the patient that preserves a normal (or, more often, increased) body mass index and limb circumferences within normal limits. This condition, which is called “sarcopenic obesity”, has a prevalence between 20 and 35% in patients with cirrhosis, and is associated with an increased risk of mortality [7]. Moreover, the prevalence of sarcopenia increases according to the grade of liver fibrosis, with a prevalence of 8.7% in patients without NAFLD, 17.9% in patients with NALFD and 35% in patients with NASH [8]. Moreover, many studies showed how sarcopenia in NAFLD represents a risk factor of advanced fibrosis independently from other metabolic risk factors [9].

In conclusion, NAFLD is a complex condition, which is part of a multisystemic syndrome in which all different factors influence each other. The patognomonic excess of adipose tissue storage determines alterations at the peripheral muscle level, leading to sarcopenia and, more often, sarcopenic obesity. Thence, a self-feeding pattern establishes, worsening the clinical history and the outcome of these patients. This is an aspect to keep well in mind, given the impact that sarcopenia has on mortality in patients with cirrhosis and especially considering how underestimated is the reduction in muscle mass and physical strength in these patients who, at least in appearance, seem to have something “in excess” rather than “in defect”.

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