Leptin Receptor Lys656Asn Polymorphism Is Associated with Decreased Leptin Response and Weight Loss Secondary to a Lifestyle Modification in Obese Patients

Background

Human obesity is characterized by high levels of leptin, and it has been suggested that obese patients may be leptin resistant. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on leptin response and weight loss secondary to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients.

Methods

A population of 67 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of lifestyle modification program, bipolar electrical bioimpedance, blood pressure, and a serial assessment of nutritional intake with 3 days written food records and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% carbohydrates, 25% lipids and 23% proteins). The exercise program consisted of aerobic exercise for at least three times per week (60 min each). Statistical analysis was performed for the combined Lys656/Asn656 and Asn656/Asn656 as mutant group and type Lys656/Lys 656 as wild-type second group.

Results

Sixty seven patients gave informed consent and were enrolled in the study. The mean age was 45.7 ± 16.6 years and the mean BMI 34.1 ± 5.1, with 18 males (26.9%) and 49 females (73.1%). Thirty six patients (10 males/26 females) (46.8%) had the genotype Lys656/Lys 656 (wild-type group) and 31 patients (8 males/23 females) (46.3%) Lys656/Asn656 (n = 28, 41.8%) or Asn656/Asn656 (n = 3, 4.5%) (mutant group). The percentage of responders (weight loss) was similar in both groups (91.7 vs. 87.1%).

In wild-type group (responders and nonresponders), BMI, weight, fat mass, systolic blood pressure and waist circumference decreased. In mutant group, BMI, weight and waist circumference decreased. No differences were detected between basal values in both groups. Only leptin levels decreased significantly in wild-type group (11.5%; p <0.05) (57.3 ± 31.5 ng/mL vs. 45.8 ± 29.3 ng/mL; p <0.05). In mutant group, leptin increased without statistical differences (0.44%; ns).

Conclusions

Patients with Asn656 allele of LEPR gene have a different response than wild-type patients, and Lys656Lys patients have a significant decrease in weight, BMI, fat mass, waist circumference, systolic blood pressure and leptin levels.

Key Words: Lys656Asn LEPR, Diet, Exercise, Obesity