According to that study, a successful strategy to improve insulin sensitivity in subjects with NAFLD, obesity, and insulin resistance must address the increase in physical activity (with increased irisin and increased energy expenditure) and the fact that caloric restriction improves insulin sensitivity in other ways (for example, increasing adiponectin production) that are different from those of myokines. Here, FNDC5 is linked to obesity due to melanocortin 4 receptor deficiency.