With great interest, we read the recent article by Desai et al regarding the effect of maternal metformin treatment on fetal inflammation in a rat model of obesity and metabolic syndrome (MetS). The authors very clearly discussed the relation between metformin treatment and inflammation. They concluded that diet-induced obesity/MetS during pregnancy significantly enhanced fetal and placental cytokine production. Maternal metformin reduced fetal cytokine levels, in addition; metformin treatment of a placental cell line suppressed tumor necrosis factor alpha–induced interleukin-6 levels by nuclear factor kappa B inhibitor. In addition to their fluent discussion, we aimed to emphasize the possible other effective mechanism of metformin treatment on MetS and obesity: the contribution of autonomic nervous system function.

MetS is a combination of metabolic abnormalities, such as abdominal obesity, dyslipidemia, hypertension, and impaired glucose metabolism, which is associated with insulin resistance. Recently, we found that autonomic nervous system function is also impaired in this disease group. Previously, Erdem et al showed that the relationship between MetS and impaired autonomic nervous system function is detected by different methods, in MetS patients without coronary artery diseases and diabetes mellitus (DM). Together with this, MetS-related impairment in autonomic nervous system function is thought to play a central role in the risk of cardiovascular death.

Metformin is an insulin sensitizer that has been shown to reduce insulin resistance and hyperglycemia with DM and to reduce progression of impaired glucose tolerance to DM in those without DM. Interestingly, Manzella et al showed beneficial effect of metformin on autonomic control. They concluded that metformin treatment was useful for improving cardiac sympathovagal balance in obese type 2 diabetic patients.

We believe that the effect of metformin on autonomic nervous system function may have a role in the result of the article by Desai et al. We hope that the above-mentioned items would add to the value of the well-written article of Desai et al regarding the effect of maternal metformin treatment to the fetal inflammation in a rat model of obesity and MetS.