Reply
Authors: Ho Cheol Hong, Kyung Mook Choi
Journal: Hepatology (2013)

We thank Issa et al. for their interest in our article, and we read their results carefully. Recently, nonalcoholic fatty liver disease (NAFLD) and age-related muscle loss (sarcopenia) have become actively studied in the research field of metabolic disorders. These diseases are regarded as the causal factors inducing metabolic complications in obese and elderly populations.1 Furthermore, both liver and muscle are target organs for insulin action and insulin resistance is known as a key factor for the development of NAFLD and sarcopenia.2 In addition to insulin resistance, NAFLD and sarcopenia seem to share similar pathophysiological backgrounds, such as chronic inflammation, vitamin D deficiency, oxidative stress, and decreased physical activity.1, 3 However, little is known about the direct association between NAFLD and sarcopenia. The study conducted by Issa et al. targeted people who were clearly identified to have nonalcoholic steatohepatitis (NASH) or NASH-related cirrhosis through a liver biopsy. As the histological change of liver was becoming more severe, the decrease in muscle mass (cross-sectional area of the spinal muscle mass in abdominal computed tomography [CT]) was more prominent. Moreover, the degree of NAFLD was related to the degree of fatty infiltration in muscle. These results suggest that ectopic fat in liver or muscle are closely associated with skeletal muscle mass. Since there was progressive muscle wasting according to the liver histology and sarcopenia worsened with progression to cirrhosis, this study supports the hypothesis regarding the quantitative relationship between NAFLD and sarcopenia. Our study revealed an increased insulin resistance index in subjects with sarcopenia compared to those without sarcopenia.4 The insulin resistance index had a significant negative correlation with both skeletal muscle mass index (SMI) and liver attenuation index (LAI), which reflects fatty infiltration in the liver. Furthermore, the association between NAFLD and SMI persisted even after adjusting for potential confounding factors including insulin resistance and inflammation. These results suggest that other factors in addition to insulin resistance and inflammation may mediate the interrelationship between sarcopenia and NAFLD, possibly including myokines. Muscle-derived interleukin-6 (IL-6) is known to be involved in glucose and lipid metabolism, maintenance of muscle mass and strength, and systemic inflammation.5 Recently, Bostrom et al.6 reported that irisin is an exercise-induced novel myokine that derives brown-fat-like conversion of white adipose tissue. Irisin is suggested as a circulating factor that mediates crosstalk between skeletal muscle and adipose tissue. Recently, it has been reported that body size phenotype can be different among obese people with the same body mass index (BMI).7 It has not been clearly elucidated yet regarding the underlying mechanisms. One of the potential underlying mechanisms, fatty infiltrations on the ectopic site, might be a factor inducing the phenotypical differences in obesity. Stefan et al.8 demonstrated that hepatic fat content might be more important than visceral fat in the determination of the harmful phenotype in obesity. Moreover, in obese postmenopausal women, metabolically healthy but obese (MHO) individuals have a lower risk of NAFLD compared to metabolically abnormal obese (MAO) individuals.9 We recently observed that low muscle mass may be associated with different metabolic consequences according to body size phenotype, such as MHO or metabolically abnormal but normal weight (MANW).10 These results suggest that the comprehensive understanding regarding the relationship between NAFLD and sarcopenia may help to set up the direction for future research to reduce the metabolic complications caused by obesity and aging. Ho Cheol Hong, M.D. Kyung Mook Choi, M.D., Ph.D. Division of Endocrinology and Metabolism Department of Internal Medicine College of Medicine Korea University Seoul, Korea