Antibodies Reactive to Leptin in Adults with Type 2 Diabetes and Its Relationship with Clinical, Metabolic and Cardiovascular Risk Parameters.

BACKGROUND AND AIMS: Patients with obesity and type 2 diabetes (T2D) have shown alterations in the affinity of IgG anti-leptin antibodies which are possibly related to metabolic alterations. In the present exploratory study, we analyzed serum samples from adults with T2D classified by body mass index (BMI) and evaluated the relationship of IgG anti-leptin antibodies with body composition, metabolic and cardiovascular risk parameters. METHODS: Serum IgG anti-leptin antibodies (total, free and immune complexes fractions) were measured by in-house ELISA. Body composition, metabolic biomarkers (glucose, glycated hemoglobin, lipid profile, insulin, leptin) and cardiometabolic risk indexes (AIP, HOMA-IR, HOMA-ß) were evaluated in one hundred T2D patients. RESULTS: Patients with T2D and obesity presented a decrease in the percentage of IgG anti-leptin immune complexes compared to patients with T2D and overweight (p < 0.0053). Negative correlations of IgG anti-leptin immune complexes with triglycerides (TG) (r=-0.412, p = 0.023) and VLDL-C (r=-0.611, p = 0.017) were found in normal weight T2D patients. Free IgG anti-leptin antibodies correlated positively with TC (r = 0.390, p = 0.032) and LDL-C (r = 0.458, p = 0.011) in overweight individuals with T2D. Finally, total IgG anti-leptin antibodies correlated positively with leptin hormone levels (r = 0.409, p = 0.024) and negatively with HOMA-IR (r =-0.459, p = 0.012) in T2D patients with obesity. CONCLUSIONS: The decrease of IgG anti-leptin immune complexes observed in patients with T2D and obesity suggests a reduction in antibody affinity to the hormone that may impact its transport and signaling, lipid, lipoprotein and insulin metabolism.

Leptin-reactive antibodies are distinctly correlated with body composition parameters and metabolic risk indexes in children and adolescents.

Studies have demonstrated the presence of low-affinity immunoglobulins (Igs) directed to leptin, a key hormone of the neuroendocrine axis that regulates appetite and metabolism, in adult healthy subjects, patients with obesity, and type 2 diabetes mellitus. In the present exploratory study, IgG leptin-reactive antibodies were analyzed for the first time in children and adolescents according to body mass index (BMI) and were correlated with biochemical profile (lipid profile, insulin, glucose, and leptin) and metabolic risk indexes [homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for ß-cell function (HOMA-ß), atherogenic index of plasma (AIP)]. One hundred and thirty-six participants were included (children n = 63, adolescents n = 73). An in-house enzyme-linked immunosorbent assay (ELISA) test was performed to measure IgG anti-leptin antibodies (free, total, and immune complexes). In adolescents, free and total IgG anti-leptin antibodies levels were higher in groups with overweight or obesity than in normal-weight group (P < 0.01), while in children, the total fractions were lower in groups with overweight and obesity than in normal weight (P < 0.02). Immune complexes percentage showed opposite correlations with BMI in children (r = 0.4004, P = 0.0473) and adolescents (r = -0.3983, P = 0.0133). IgG anti-leptin antibodies were also correlated with HOMA-IR in children (r = -0.4569, P = 0.0217) and adolescents (r = -0.3589, P = 0.0316), and with AIP (r = -0.3608, P = 0.0261) in adolescents. Our data suggest that the production and affinity of IgG anti-leptin antibodies can be affected by age, body composition, and metabolic conditions; additionally, in normal conditions, IgG anti-leptin antibodies may have a protective role in insulin resistance and cardiovascular events.

IgG antibodies reacting with ghrelin and leptin are correlated with body composition and appetitive traits in young subjects.

Appetitive traits are important behavioural characteristics affecting eating and body composition. Ghrelin and leptin are two key hormones regulating appetite and metabolism. Recent studies have reported the presence of autoantibodies (autoAbs) directed to ghrelin and leptin in healthy individuals as well as affinity alterations in eating disorders such as anorexia nervosa and hyperphagic obesity. Nevertheless, the relationship of these autoAbs with appetitive traits is unknown. The goals of this exploratory study were to analyze circulating IgG autoAbs reacting to ghrelin and leptin and evaluate their relationship with body composition parameters and appetitive traits. This cross-sectional study included 180 young subjects (20 ± 2 years) that underwent body composition evaluation. Seven appetitive traits were assessed with AEBQ-Esp and were classified as low-score or high-score. A validated in-house ELISA test was performed to measure IgG ghrelin and leptin-reactive autoAbs in its free, total, and immune complexes fractions. Free IgG ghrelin-reactive were significantly higher in women than in men. Immune complexes of IgG-ghrelin were positively correlated with waist-hip ratio in the total cohort. In women, free IgG leptin-reactive were positively correlated with body fat percentage and waist-hip ratio, whereas in men, immune complexes of IgG-leptin were positively correlated with body fat percentage. Women with a low-score for 'enjoyment of food', exhibited higher levels of IgG ghrelin-reactive autoAbs on its free form than the high-score group. Men with a high-score for 'emotional undereating' had higher levels of free IgG leptin-reactive autoAbs than the low-score group. The correlation of these autoAbs with anthropometric parameters and appetitive traits in young subjects support its role as carriers and modulators of the biologic functions of ghrelin and leptin and suggest a novel role in eating behaviour through appetitive traits.

ABCA1 gene R1587K polymorphism could be associated with metabolic syndrome and increased plasma triglyceride concentration in adults from northern Mexico.

INTRODUCTION: Objectives: to investigate the relationship of R1587K genotypes with cardiovascular (CV) risk, metabolic syndrome (MetS), lipid profile, paraoxonase-1 (PON1) activity, and anti-oxLDL titers. Methods: we performed a cross-sectional study in 57 northern Mexican adults with no reported diseases. The ABCA1 R1587K SNP was detected by real-time polymerase chain reaction (qPCR) using TaqMan allelic discrimination probes. We evaluated the relationship of R1587K with metabolic syndrome and clinical parameters including lipid profile, glucose and insulin, PON1 activity and concentration, anti-oxLDL antibodies, anthropometry and body-composition parameters, and the atherogenic index of plasma calculation. Results: our results show higher triglyceride levels in the RK + KK carriers as compared to RR carriers (p = 0.031). An association between the RK + KK genotype and the presence of MetS (OR = 4.566, 95% CI = 1.386-14.92, p = 0.010) and a tendency towards high CV risk (OR = 3.317, 95% CI = 0.910-8.611, p = 0.069) was observed in comparison to RR carriers; however, there were no differences in HDL-C levels, PON1 activity and concentration, and anti-oxLDL titers among the R1587K genotypes. Conclusions: in the northern Mexican population, the ABCA1 gene R1587K SNP is present and the RK + KK genotypes are associated with MetS and increased triglyceride concentrations; therefore, it could be a CV risk biomarker. Nevertheless there is a need for further confirmation in longitudinal studies.

INTRODUCCIÓN: Objetivo: investigar la relación de los genotipos del SNP R1587K con el riesgo cardiovascular (CV), el síndrome metabólico (SM), el perfil de lípidos, la actividad de paraoxonasa 1 (PON1) y los anticuerpos contra las LDL oxidadas (anti-oxLDL). Métodos: se realizó un estudio transversal con 57 adultos del norte de México que reportaron no tener enfermedades diagnosticadas. El SNP R1587K del gen ABCA1 se detectó a través de PCR en tiempo real (qPCR) usando sondas TaqMan para discriminación alélica. Para evaluar la asociación del SNP R1587K con el SM y determinados parámetros clínicos se determinaron el perfil de lípidos, los niveles de glucosa e insulina, la actividad y concentración de PON1, los anticuerpos anti-oxLDL, los parámetros antropométricos y de composición corporal, y el cálculo del índice aterogénico en plasma. Resultados: los resultados mostraron mayores niveles de triglicéridos en los portadores del genotipo RR + KK que en los portadores de RR (p = 0,031). Se observó una asociación entre el genotipo RK + KK y la presencia de SM (OR = 4,566, IC 95% = 1,386-14,92, p = 0,010) y una tendencia hacia un mayor riesgo cardiovascular (OR = 3,317, IC 95% = 0,910-8,611, p = 0,069) al compararlos con los portadores de RR. No se encontraron diferencias en los niveles de HDL-C, la actividad y concentración de PON1 y los anti-oxLDL entre los genotipos R1587K. Conclusiones: el SNP R1587K del gen ABCA1 se encuentra presente en la población del norte de México y el genotipo RK + KK se asocia con el SM y concentraciones elevadas de triglicéridos, por lo que este SNP podría ser un biomarcador de riesgo cardiovascular. Sin embargo, se necesita confirmación a través de estudios longitudinales. .

IgG Anti-ghrelin Immune Complexes Are Increased in Rheumatoid Arthritis Patients Under Biologic Therapy and Are Related to Clinical and Metabolic Markers.

Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with increased risk of cardiovascular disease and metabolic alterations. The mechanisms underlying these alterations remain unclear. Ghrelin is a gastrointestinal hormone with potent effects on food intake, body weight, metabolism, and immune response. Recent studies reported the presence of anti-ghrelin autoantibodies in healthy subjects and the levels and affinity of these autoantibodies were altered in anorectic and obese individuals. In this cross-sectional study we analyzed anti-ghrelin autoantibodies in RA patients and evaluated its relationship with clinical, body-composition and metabolic parameters. Clinical measurements of RA patients included the disease activity score-28 (DAS-28), inflammatory biomarkers, autoantibodies (RF and anti-CCP), body composition, glucose and lipid profile. Serum ghrelin levels were measured by enzyme-linked immunosorbent assay (ELISA). Free and total anti-ghrelin autoantibodies quantification (IgG and IgA isotypes) was performed by in-house ELISA. RA patients had lower IgG anti-ghrelin autoantibodies levels and higher immune complexes percentage (IgG+ghrelin) compared to the control group, while the IgA anti-ghrelin autoantibodies showed no significant differences. In the bivariate analysis, the percentage of IgG anti-ghrelin immune complexes positively correlated with BMI and ghrelin whereas in the multivariate regression model, the variables associated were DAS-28, body weight, visceral fat, LDL-C and TG (R 2 = 0.72). The percentage of IgA anti-ghrelin immune complexes positively correlated with RF and anti-CCP and the multivariate regression model showed an association with RF and body fat percentage (R 2 = 0.22). Our study shows an increased percentage of IgG anti-ghrelin immune complexes in RA patients despite ghrelin levels were similar in both groups, suggesting an increase in the affinity of these autoantibodies toward ghrelin. The associations found in the multiple regression analysis for anti-ghrelin immune complexes support the previously reported functions of these natural autoantibodies as carriers and modulators of the stability and physiological effect of the hormone. However, in RA both the disease activity and the RF appear to influence the formation of these anti-ghrelin immune complexes.