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Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes.

ABSTRACT: Obese subjects display elevated plasma levels of leptin reflecting the phenomenon of leptin resistance. Here, we aimed to determine whether leptin-reactive immunoglobulins (Ig) are present in obese and type 2 diabetes (T2D) patients and whether their plasma levels and affinity kinetics may correlate with obesity and diabetes markers. We show that leptin levels are increased in obese patients with and without T2D. Although mean plasma levels of leptin-reactive IgG were similar between study groups, IgG in obese non-diabetic patients had increased dissociation rate and lower affinity (increased dissociation equilibrium constant value; KD). In controls and diabetic patients, the association rates of leptin IgG correlated negatively with obesity and diabetes markers, respectively. In contrast, KD values correlated positively with plasma leptin levels and obesity traits in our cohort, and with diabetes markers in both the total cohort and in the obese T2D group. Taken together, our data reveal that leptin-reactive IgG are present in healthy subjects, obese, and diabetic patients but display altered affinity kinetics in obesity. Increased IgG binding to leptin in healthy subjects associated with lower body mass index (BMI) suggests an enhancing role of IgG in leptin signaling. Accordingly, a decreased affinity of IgG for leptin, found in obese patients, can be relevant to leptin resistance.

SUBMITTER: Bouhajja H

PROVIDER: S-EPMC5966443 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes.

Bouhajja Houda H Bougacha-Elleuch Noura N Lucas Nicolas N Legrand Romain R Marrakchi Rim R Kaveri Srini V SV Jamoussi Kamel K Ayadi Hammadi H Abid Mohamed M Mnif-Feki Mouna M Fetissov Sergueï O SO

Nutrition & diabetes 20180524 1

Obese subjects display elevated plasma levels of leptin reflecting the phenomenon of leptin resistance. Here, we aimed to determine whether leptin-reactive immunoglobulins (Ig) are present in obese and type 2 diabetes (T2D) patients and whether their plasma levels and affinity kinetics may correlate with obesity and diabetes markers. We show that leptin levels are increased in obese patients with and without T2D. Although mean plasma levels of leptin-reactive IgG were similar between study group ...[more]

PMID: 29795184

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Project description:BackgroundThis study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene LEP (A19G and G2548A) and leptin receptor gene LEPR (K109R and Q223R) and their association with fasting plasma leptin level (PLL) and obesity in a Malaysian suburban population in Kampar, Perak.MethodsConvenience sampling was performed with informed consents, and the study sample was drawn from patients who were patrons of the Kampar Health Clinic. A total of 408 subjects (mean age, 52.4 ± 13.7 years; 169 men, 239 women; 190 obese, 218 non-obese; 148 Malays, 177 ethnic Chinese, 83 ethnic Indians) participated. Socio-demographic data and anthropometric measurements were taken, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe LEP A19G, G2548A and LEPR K109R, Q223R variant allele frequencies were 0.74, 0.67 and 0.61, 0.79, respectively. The genotype and allele distributions of these gene variants were significantly different among ethnic groups, but not among body mass index (BMI) classes. Subjects with LEPR K109 and Q223 allele had significantly higher systolic blood pressure and adiposity indices after adjustment for ethnicity (higher BMI, total body and subcutaneous fat; lower skeletal muscle percentage). Subjects with LEPR 109R allele had lower PLL than their wild-type allele counterparts. The influence of LEP A19G and G2548A SNPs on blood pressures, anthropometrics, and PLL was not evident. Interestingly, synergistic effect of the LEP and LEPR SNPs was observed as subjects homozygous for all four SNPs studied exhibited significantly higher subcutaneous fat and PLL than those with other genotype combinations.ConclusionsThe LEP and LEPR SNPs in this study may not be an obesity marker among Malaysians in this population, but were associated with ethnicity. Our findings suggest that each of these SNPs contributes to minor but significant variation in obesity-related traits and in combination they display synergistic effects on subcutaneous fat and PLL.

Dataset Information

Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes.

Publications

Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes.

Similar Datasets

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