Context: Obesity is frequently associated with left ventricular hypertrophy, even when uncomplicated by hypertension or diabetes mellitus. Left ventricular hypertrophy is an important risk factor for congestive heart failure. Objective: The objective of this study was to evaluate the relationship between leptin and left ventricular mass in uncomplicated, morbid (grade 3) obesity and the existence of leptin receptors and intracellular signaling proteins in the human heart. Design: Left ventricular mass (LVM) was calculated through electrocardiogram reading in normotensive grade III obese patients (World Health Organization classification) undergoing bariatric surgery [laparoscopic adjustable gastric banding (LAGB)] at baseline and 1 yr later. The control group was composed of healthy lean normotensive subjects. Leptin receptors were detected by PCR and immunocytochemistry in human heart biopsies. Setting: This study was performed at university hospitals. Patients: Thirty-one grade 3 obese patients and 30 healthy nonobese normotensive, age- and sex-matched control subjects were studied. Intervention: Obese subjects underwentLAGBto induce weight loss and were evaluated at baseline and after 1 yr. Results: LVM, plasma leptin, glucose, insulin levels, and homeostasis model assessment index were higher in obese than in lean controls (P _ 0.01); at univariate regression analysis, LVM correlated with body mass index, leptin, and homeostasis model assessment index; at multiple regression analysis, LVM only correlated with leptin levels (P _ 0.001). Obese subjects were reevaluated 1 yr after LAGB, when their body mass index changed from 46.2 _ 1.24 to 36.6 _ 1.05 kg/m2 (P _ 0.01); the decrease in LVM correlated only with the decrease in leptin levels (P_0.01).Wedemonstrated that long and short isoforms of the leptin receptor and intracellular proteins mediating leptin signaling were expressed in human heart by RT-PCR, immunocytochemistry, or both methods. Conclusions: These data suggest that leptin could contribute to the left ventricular hypertrophy in humans.