TNF and obesity due to melanocortin 4 receptor deficiency: In recent years, an attractive hypothesis has emerged proposing that those cytokines such as TNF-α and IL-6 produced by adipose tissue may be responsible for insulin resistance in obesity [59]; indeed, the expression or production of these cytokines was shown to be directly related to the degree of obesity of the subjects, and thus might be involved in obesity-related insulin resistance [59]–[63].