Reduced cardio-respiratory fitness in obesity with and without nonalcoholic fatty liver disease
Authors: Melania Manco, Valerio Nobili
Journal: Hepatology (2008)

We read with great interest the study by Krasnoff et al. in a recent issue of HEPATOLOGY.1 The concept that health-related fitness and physical activity are beneficial in patients with nonalcoholic fatty liver disease (NAFLD) and, largely and generally, features of the metabolic syndromes, appears to be intuitive. Nonetheless, the authors address a matter which is very relevant but often disregarded in clinical practice. Therapeutic guidelines for individuals with NAFLD (as well as with simple obesity) suggest weight loss and increased physical activity, but the capacity for performing physical activity is never assessed before prescribing it. The authors observed worse capacity for cardio-respiratory fitness associated with increasing NAFLD activity and disease severity as well as reduced muscle strength. Thus, it can be argued that caution should be adopted and strict monitoring ensured by a cardiologist when an individual with NAFLD is instructed to a lifestyle program of physical activity. In our experience, children with NAFLD show a significantly reduced capacity for performing physical activity compared with obese insulin-resistant children with no evidence of fatty liver disease. Therefore, a specialized cardiologist should enter the multidisciplinary team which takes care of children with NAFLD.2 As far as any causative relation between reduced cardio-respiratory fitness and NAFLD is concerned, several questions remain open for discussion, and they have not been addressed in the study by Krasnoff et al. The study design lacks two groups of normal-weight subjects serving as controls, one with both insulin resistance and NAFLD and the other one with insulin resistance alone, and thus does not allow us to rule out the confounding relations among body weight, insulin resistance, NAFLD, and reduced cardio-respiratory fitness. The question is the extent to which NAFLD impairs the capacity for exercise in respect to insulin resistance and/or obesity without NAFLD. Insulin resistance associates per se with an impaired activity of the sympathetic nervous system,3 which augments the cardiovascular risk but also reduces the ability to perform physical exercise. Furthermore, the reduced lean mass ratio with body weight, which also characterizes obesity (lean mass, according to table 2 in the article, is approximately 60%-65%), the different proportion of small fibers,4 and the increased deposition of triglycerides in the muscle tissue coupled with the inability to oxidize them correctly5 can contribute to the phenomena observed in the study, independent of NAFLD. In conclusion, we agree completely with the authors about the rationality of recommending physical exercise for patients with NAFLD, although we would emphasize the need to personalize any program of physical exercise along with monitoring the individual response in the clinical practice, and we encourage dissecting the single contributions of insulin resistance, impaired body composition, and NAFLD to reduced cardio-respiratory fitness in future research studies. Melania Manco M.D., Ph.D.*, Valerio Nobili M.D. , * Scientific Directorate, Bambino Gesù Hospital and Research Institute, Rome, Italy, Liver Unit, Bambino Gesù Hospital and Research Institute, Rome, Italy.