Role of leptin in the development of cardiac hypertrophy in experimental animals and humans.

Hypertrophy in Experimental Animals and Humans To the Editor: Barouch et al1 recently published a well-designed study demonstrating that left ventricular hypertrophy (LVH) occurs in mice that are either leptin-deficient (ob/ob) or leptin-resistant (db/db). They also found that systemic administration of leptin to the leptin-deficient animals attenuated LVH more than would be predicted by the leptin-induced hypophagia and weight loss. These observations suggest that leptin may have a direct inhibitory effect on cardiac hypertrophy.1 We have recently examined the association between systemic leptin levels and cardiovascular indexes in a population of healthy obese and lean men.2,3 In addition to showing that the obese had greater absolute and height-indexed left ventricular (LV) mass (confirming the association between obesity and LVH in this normotensive population2–4), we also found a positive association between serum leptin and height-indexed LV mass,2 which did not persist after adjustment for body mass index.2 The data by Barouch et al1 in experimental animals corroborate our observations in humans2,3 and provide a potential pathophysiological explanation. With rare exceptions, human obesity is associated with hyperleptinemia and apparent leptin resistance.5 LVH in this group of patients could be due to the lack of the leptin attenuating effect on LV mass, similar to the occurrence of LVH in the hyperleptinemic, leptin-resistant db/db mice. It remains to be established whether pharmacological amelioration of leptin resistance will either prevent or, at least, attenuate LVH in rodent and human obesity.