Leptin infusion completely reversed the increase in left ventricular wall thickness in obese mice, whereas caloric restriction did not, indicating leptin has weight-independent antihypertrophic effects.
Does leptin infusion reverse left ventricular hypertrophy independently of weight loss in leptin-deficient mice?
Leptin has direct antihypertrophic effects on the heart independent of weight loss, suggesting that disruption of leptin signaling contributes to obesity-associated left ventricular hypertrophy.
BACKGROUND: Whether left ventricular hypertrophy (LVH) in obesity results from increased hemodynamic load or altered neurohormonal signaling remains controversial. Dysregulation of leptin, a neurohormone essential to energy homeostasis, is implicated in the pathogenesis of obesity. Because leptin has cardiovascular bioactivity, we hypothesized that disruption of leptin signaling mediates the development of obesity-associated LVH. METHODS AND RESULTS: We measured left ventricular (LV) wall thickness and LV mass with echocardiography in mice lacking leptin (ob/ob, n=15) or functional receptor (db/db, n=10) and controls at 2, 4, and 6 months of age. None of the mice had LVH at 2 months. Progressive obesity developed in ob/ob and db/db mice. At 6 months, LVH occurred in ob/ob and db/db compared with controls. We observed corresponding myocyte hypertrophy by light microscopy. To separate the direct contribution of leptin deficiency from mechanical effects of obesity, we induced weight loss in 6- to 8-month-old ob/ob mice either by leptin infusion or caloric restriction. Mice in both groups lost similar weight compared with placebo-treated controls. Leptin infusion completely reversed the increase in wall thickness with partial resolution of myocyte hypertrophy, whereas calorie-restricted mice had no decrease in wall thickness and a lesser change in myocyte size. CONCLUSIONS: Together these data show that the effect of leptin on LV remodeling is not attributable to weight loss alone, indicating that leptin has antihypertrophic effects on the heart, either directly or through a leptin-regulated neurohumoral pathway. Disruption of leptin signaling may represent a novel mechanism in LVH and related cardiovascular disorders.
Barouch et al. (Tue,) conducted a other in Cardiac hypertrophy in obesity. Leptin infusion vs. Caloric restriction and placebo was evaluated on Left ventricular wall thickness and LV mass. Leptin infusion completely reversed the increase in left ventricular wall thickness in obese mice, whereas caloric restriction did not, indicating leptin has weight-independent antihypertrophic effects.