Sex-specific effect of BMI on insulin sensitivity and TNF-α expression

Obesity is a major predisposing risk factor for the development of insulin resistance. Recently, a sexual dimorphism in the relationship between body mass index (BMI) and insulin resistance has been reported, with the deleterious effect of increasing BMI being more evident in men than in women [1]. To the best of our knowledge, the biology underlying this sex-specific association has never been addressed. By inhibiting insulin signaling, TNF-a overexpression is the main mechanism responsible for the deleterious effect of obesity on insulin resistance [2]. It is, therefore, reasonable to address the role of TNF-a as a mediator of the sex-specific response of insulin sensitivity to the insult of increasing BMI. Accordingly, we measured both the HOMA-IR insulin resistance index and TNF-a mRNA levels (in peripheral whole blood cells; PWBC) from healthy subjects with a wide range of BMI and then looked for BMI-by-sex interaction in modulating these two variables.