OBJECTIVE: Leptin resistance is discussed to be involved in the genesis of obesity. Therefore, we hypothesized that leptin levels were negatively associated with degree of weight loss in obese children participating in a lifestyle intervention. METHODS: We studied 248 obese children aged 8-14 years attending the “Obeldicks” lifestyle intervention (mean age 10.6+/-0.2 years, 53% female, 48% pubertal, mean body mass index (BMI) 27.8+/-0.3 kg/m2, and mean standard deviation score [SDS]-BMI 2.43+/-0.03). Baseline leptin concentrations were correlated with change of weight status, waist circumference, and percentage body fat, as calculated from skinfold measurements in the one-year intervention by Pearson correlation and multiple linear regression analyses. Furthermore, the relationship between leptin and cardiovascular risk factors (insulin, insulin resistance index HOMA, blood pressure, lipids, and glucose) were analyzed. RESULTS: A total of 212 children (85%) reduced their overweight, 9 children (4%) dropped out, and 27 children (11%) did not reduce their overweight in the lifestyle intervention “Obeldicks”. The mean reduction of SDS-BMI was 0.34+/-0.02. The reduction of SDS-BMI (r=- 0.27), waist circumference (r=- 0.64), and percentage body fat (r=- 0.26) were significantly negatively associated with baseline leptin levels both in univariate analyses and in multiple regression analyses, adjusted to baseline age, BMI, gender and pubertal stage. Baseline leptin concentrations were significantly associated with BMI, pubertal stage, gender, waist circumference, and insulin, but not to any other cardiovascular risk factors in multiple regression analyses. CONCLUSIONS: The finding that baseline leptin concentrations were significantly negatively correlated with the degree of weight loss in a lifestyle intervention supports the hypothesis of leptin resistance in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

The adipocytokine leptin centrally regulates body weight by enhancing metabolic rate and signaling satiety, but it also has wide-ranging peripheral effects. Leptin receptors are expressed on vascular smooth muscle cells and have a role in maintaining vascular tone. We investigated the vascular effects of leptin repletion or calorie restriction on leptin-deficient mice (ob/ob) and a leptin antagonist on wild-type (WT) mice. Aortic compliance was assessed by the measurement of pulse wave velocity by noninvasive Doppler; blood pressure was measured by left ventricular catheterization. We found that ob/ob mice have much stiffer aortas than WT mice and that reduction in aortic stiffness was greater in ob/ob mice treated with leptin vs calorie restriction, despite similar weight loss. Interestingly, treating WT mice with a leptin antagonist increases aortic stiffness with no change in weight. Thus, we conclude that leptin is essential for maintaining normal aortic compliance independent of body weight.International Journal of Obesity advance online publication, 6 October 2009; doi:10.1038/ijo.2009.208.

J Opioid Manag. 2009 Nov-Dec;5(6):373-8.

Methylnaltrexone potentiates body weight and fat reduction with leptin.

Yuan CS, Sun S, Attele A, Wang CZ, Tong R, Israel RJ.

Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, Illinois, USA

PMID: 20073411 [PubMed - in process]

Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepRs), and intra-mNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat, and sucrose diets, yielding increased body weight and adiposity. The chronic hyperphagia of mNTS/AP LepRKD rats is likely mediated by a reduction in leptin potentiation of gastrointestinal satiation signaling, as LepRKD rats showed decreased sensitivity to the intake-reducing effects of cholecystokinin. LepRKD rats showed increased basal AMP-kinase activity in mNTS/AP micropunches, and pharmacological data suggest that this increase provides a likely mechanism for their chronic hyperphagia. Overall these findings demonstrate that LepRs in mNTS and AP neurons are required for normal energy balance control. 2010 Elsevier Inc.