Peripubertal Alterations of Leptin Levels in Patients with Autism Spectrum Disorder and Elevated or Normal Body Weight.

Leptin, which plays a key role in energy homeostasis, is known as a neurotrophic factor possibly linking nutrition and neurodevelopment. Available data on the association between leptin and autism spectrum disorder (ASD) are confusing. The aim of this study was to explore whether plasma levels of leptin in pre- and post-pubertal children with ASD and/or overweightness/obesity differ from those of BMI- and age-matched healthy controls. Leptin levels were determined in 287 pre-pubertal children (mean age 8.09 years), classified as follows: ASD with overweightness/obesity (ASD+/Ob+); ASD without overweightness/obesity (ASD+/Ob-); non-ASD with overweightness/obesity (ASD-/Ob+); non-ASD without overweightness/obesity (ASD-/Ob-). The assessment was repeated in 258 of the children post-pubertally (mean age 14.26 years). There were no significant differences in leptin levels either before or after puberty between ASD+/Ob+ and ASD-/Ob+ or between ASD+/Ob- and ASD-/Ob-, although there was a strong trend toward significance for higher pre-pubertal leptin levels in ASD+/Ob- than in ASD-/Ob-. Post-pubertal leptin levels were significantly lower than pre-pubertal levels in ASD+/Ob+, ASD-/Ob+, and ASD+/Ob- and higher in ASD-/Ob-. Leptin levels, elevated pre-pubertally in the children with overweightness/obesity as well as in children with ASD and normal BMI, decrease with age, in contrast to the increasing leptin levels in healthy controls.

Leptin and Ghrelin in Excessive Gestational Weight Gain-Association between Mothers and Offspring.

Two-thirds of pregnant women exceed gestational weight gain recommendations. Excessive gestational weight gain (EGWG) appears to be associated with offspring's complications induced by mechanisms that are still unclear. The aim of this study was to investigate whether umbilical cord leptin (UCL) and ghrelin (UCG) concentrations are altered in full-term neonates born to EGWG mothers and whether neonatal anthropometric measurements correlate with UCL and UCG levels and maternal serum ghrelin and leptin as well as urine ghrelin concentrations. The study subjects were divided into two groups, 28 healthy controls and 38 patients with EGWG. Lower UCL and UCG levels were observed in neonates born to healthy mothers but only in male newborns. In the control group UCG concentrations correlated positively with neonatal birth weight, body length and head circumference. In the control group maternal serum ghrelin levels correlated negatively with neonatal birth weight, body length and head circumference as well as positively with chest circumference. In the EGWG group UCG concentrations correlated negatively with neonatal birth weight and birth body length. UCL correlated positively with birth body length in EGWG group and negatively with head circumference in the control group. In conclusion, EGWG is associated with disturbances in UCL and UCG concentrations.

Fatty Acid-Binding Protein 4-An "Inauspicious" Adipokine-In Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain and Gestational Diabetes Mellitus.

The exact roles of adipokines in the pathogenesis of type 2 diabetes and obesity are still unclear. The aim of the study was to evaluate fatty acid binding protein 4 (FABP4) concentrations in the serum and urine of women with excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM) in the early post-partum period, with reference to their laboratory test results, body composition, and hydration status. The study subjects were divided into three groups: 24 healthy controls, 24 mothers with EGWG, and 22 GDM patients. Maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. Concentrations of FABP4, leptin, and ghrelin were determined via enzyme-linked immunosorbent assay (ELISA). Healthy women were characterized by the lowest serum leptin concentrations and by a negative correlation between the serum and urine FABP4 levels. Serum FABP4 levels were the highest in the GDM group. Serum FABP4 and leptin concentrations correlated positively in the GDM group. The EGWG group had the highest degree of BIA disturbances in the early puerperium and positive correlations between the urine FABP4 and serum leptin and ghrelin concentrations. The physiological and pathological significance of these findings requires further elucidation.

Ghrelin in Serum and Urine of Post-Partum Women with Gestational Diabetes Mellitus.

Women with a previous history of gestational diabetes mellitus (GDM) have a significantly increased risk of developing type 2 diabetes, obesity, and cardiovascular diseases in the future. The aim of the study was to evaluate ghrelin concentrations in serum and urine in the GDM group in the early post-partum period, with reference to laboratory results, body composition, and hydration status. The study subjects were divided into two groups, that is, 28 healthy controls and 26 patients with diagnosed GDM. The maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. The concentrations of ghrelin in the maternal serum and urine were determined via enzyme-linked immunosorbent assay (ELISA). The laboratory and BIA results of the mothers with GDM were different from those without GDM. Urine ghrelin positively correlated with serum ghrelin and high-density lipoprotein cholesterol (HDL) levels in healthy mothers. There were direct correlations between urine ghrelin and HDL as well as triglycerides levels in the GDM group. Neither the lean tissue index nor body cell mass index were related to the serum ghrelin concentrations in this group. Only the urine ghrelin of healthy mothers correlated with the fat tissue index. Our results draw attention to urine as an easily available and appropriable biological material for further studies.

Heat Shock Proteins as a Potential Therapeutic Target in the Treatment of Gestational Diabetes Mellitus: What We Know so Far.

Gestational diabetes mellitus (GDM) is a complex condition that involves a variety of pathological mechanisms, including pancreatic ß-cell failure, insulin resistance, and inflammation. There is an increasing body of literature suggesting that these interrelated phenomena may arise from the common mechanism of endoplasmic reticulum (ER) stress. Both obesity-associated nutrient excess and hyperglycemia disturb ER function in protein folding and transport. This results in the accumulation of polypeptides in the ER lumen and impairs insulin secretion and signaling. Exercise elicits metabolic adaptive responses, which may help to restore normal chaperone expression in insulin-resistant tissues. Pharmacological induction of chaperones, mimicking the metabolic effect of exercise, is a promising therapeutic tool for preventing GDM by maintaining the body's natural stress response. Metformin, a commonly used diabetes medication, has recently been identified as a modulator of ER-stress-associated inflammation. The results of recent studies suggest the potential use of chemical ER chaperones and antioxidant vitamins as therapeutic interventions that can prevent glucose-induced ER stress in GDM placentas. In this review, we discuss whether chaperones may significantly contribute to the pathogenesis of GDM, as well as whether they can be a potential therapeutic target in GDM treatment.

Serum Heat Shock Protein 90 Alpha: A New Marker of Hypertension-Induced Endothelial Injury?

BACKGROUND: Hypertension-induced endothelial dysfunction is associated with an impaired bioavailability of nitric oxide regulated through interactions between nitric oxide synthase and heat shock protein-90 (Hsp-90). The role of Hsp-90 in the development of arterial hypertension remains unclear. OBJECTIVES: The objective of the study was to evaluate serum concentrations of Hsp-90a in patients with arterial hypertension in comparison to their normotensive counterparts. MATERIAL AND METHODS: The study was performed on 49 adults (mean age 55.6 years) with an elevated waist circumference. The individuals presented no subjective feeling of any disease, admitted no drug treatment for any condition, and had not previously been diagnosed with the metabolic syndrome. Patients were screened for arterial hypertension and other component disorders of the metabolic syndrome. Hsp-90a concentrations were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Twenty-eight subjects were diagnosed with arterial hypertension, while 21 individuals had normal blood pressure. Twenty-five patients satisfied the metabolic syndrome diagnostic criteria. Hsp-90a concentrations were significantly higher (p = 0.002) in the individuals with arterial hypertension than in their normotensive counterparts (median ± interquartile range): 19.42 ng/mL ± 5.17 vs. 16.86 ng/mL ± 3.18. The concentrations of Hsp-90a correlated positively with systolic blood pressure (R = 0.39; p = 0.005) and diastolic blood pressure (R = 0.29; p = 0.046). CONCLUSIONS: An increase in Hsp-90a concentrations in patients with arterial hypertension may be a compensatory mechanism for the impaired bioavailability of nitric oxide. The role of Hsp-90a as an early marker of hypertension-associated endothelial injury should be confirmed in further studies on a larger group of patients.

An Interplay between Obesity and Inflammation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is traditionally defined as hyperglycemia first detected in pregnancy. The risk of GDM is much higher among obese women than in their lean counterparts. An excess of adipose tissue leads to immune and inflammatory responses of both white adipose tissue and the placenta, contributing to systemic inflammation. Although the significance of both obesity and inflammation is relatively well characterized in GDM, the molecular mechanisms involved are not fully defined and require further study. In recent years huge progress has been made in identifying the intracellular signaling pathways involved in the pathophysiology of GDM. However, currently available data regarding inflammation and obesity in women with GDM are still conflicting or incomplete. We discuss selected aspects of the problem and propose future directions for research in the hope of achieving a better understanding of the disease. In particular, this review highlights recent studies exploring molecular alterations related to insulin resistance, inflammation of the adipose tissue and the placenta, lipotoxicity or endotoxemia.