leptin and Intellectual-Disability

The metabolic effects of a biguanide, metformin, on glycemic control and eating behavior were investigated in 16 type 2 diabetic subjects with mental retardation who were habitual overeaters and had difficulty in controlling their appetites. The subjects (n = 16) received metformin (750 mg/day) for 6 months and body weight, body mass index (BMI) were measured monthly. They had repetitive metabolic and hormonal studies. Their eating behavior was analyzed by questionnaires given by their guardians before and after treatment. Metformin treatment significantly reduced their body weights (p < 0.01), body mass index (BMI) (p < 0.01), the levels of HbA1c (p < 0.001), fasting blood glucose (FBG) (p < 0.05), serum insulin (p < 0.05), C-peptide (p < 0.01), triglyceride (p < 0.01), and total cholesterol (p < 0.05). Insulin resistance index (FBG (mg/dl) x serum insulin levels ( micro U/ml) x 1/405) was significantly reduced after 1-month treatment. The serum leptin levels were significantly decreased after 4 month's treatment and thereafter (p < 0.05). Analysis of the questionnaires before and after treatment showed that the daily intake of regular and additional foods significantly decreased after treatment (p < 0.01 and p < 0.001, respectively) with improvements of eating behavior. We conclude that metformin may have beneficial effects not only to control glycemia but also to correct eating behavior in obese type 2 diabetic patients with the difficulty in controlling their appetites. The improvement was related to the reduction of insulin resistance and serum leptin levels.

Topics: Adult; Blood Glucose; Body Mass Index; Cholesterol; Diabetes Mellitus, Type 2; Energy Intake; Feeding Behavior; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Intellectual Disability; Leptin; Male; Metformin; Obesity; Surveys and Questionnaires; Treatment Outcome; Triglycerides

Patients with intellectual disabilities are shown to have a limited capacity for cooperation, communication,and other biological consequences, which significantly require a specialized interest in healthcare professionals worldwide.. In this respect, the present study was designed to evaluate the levels mineral elements, and their correlation with oxidative stress markers and adiposity markers; leptin (L), adiponectin (A), and L/A ratio in adolescents with intellectual disabilities.. A total of 350 schoolchildren aged (12-18 years) were randomly invited to participate in this prospective, observational study. Only 300 participants agreed to participate in this study. According to Intelligence quotients scores (IQ) measured by WISC-III, the participants were classified into two groups; the healthy control group (no = 180; IQ = 90-114); and the moderate intellectual disability (MID) group (no = 120; IQ = 35-49). Adiposity markers; body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), physical activity scores, adipokines biomarkers; leptin, adiponectin, L/A ratio, oxidative stress, and plasma mineral elements were evaluated by prevalidated questionnaires, inductively coupled plasma-mass spectrometry (ICP-MS), colorimetric, and immunoassay techniques.. Intellectual disability of moderate type was reported in 40% of the studied populations most of them are men aged 12-18 years (66.6% for men vs. 33.3 for females). Obesity was shown to be associated with the degree of intellectual disability of the students. There was a significant (P = 0.001) increase in the BMI, WHR, and WHtR scores as obesity markers with poor physical activity (P = 0.01) in students with poor disability compared to healthy controls (HC). The levels of leptin (P = 0.001), adiponectin (P = 0.01), and L/A ratio (P = 0.01) as adiposity biomarkers were significantly increased in students with MID compared to healthy controls. Also, oxidative stress measured by malondialdehyde (MDA) (P = 0.01) and total antioxidant capacity (TAC) (P = 0.01) were significantly increased in students with MID compared to healthy control subjects. In addition, mineral elements were shown to be linked with intellectual disability. The data showed that the levels of Fe, Mn, Zn, Hg, Pb, Ca, Cr, Mg, and Ni significantly (P = 0.001) increased, and the levels of Al, Na, K, Cu, and Zn/Cu ratio significantly (P = 0.001) decreased in subjects with MID compared to healthy controls. Correlation analysis concluded that changes in mineral elements significantly correlated with adiposity markers, oxidative stress, and the scores of intellectual disability (WISC III-IQ score).. The intellectual disability of moderate type (MID) was associated with abnormal changes in the levels of essential mineral elements and adipokines and increased levels of cellular oxidative stress. Thus, evaluating plasma mineral elements and adipokines levels could be a potential diagnostic parameter for diagnosing MID.

Topics: Adipokines; Adiponectin; Adiposity; Adolescent; Child; Female; Humans; Intellectual Disability; Leptin; Male; Minerals; Obesity; Prospective Studies

DEHP is a plasticizer which has been used in plastic products of everyday use for decades. Studies in mice and murine cell culture models identified DEHP as an endocrine disruptor that may also act as an obesogen. As this is of high concern in respect of the worldwide obesity epidemic, our aim is the translation of these findings into a human model system. On the basis of DOHaD, we investigated the influence of an environmentally relevant dose of DEHP [50 µg/ml] on adipogenesis in the human cell culture model SGBS. Pre-adipocytes were exposed to DEHP and differentiated into mature adipocytes. At different stages of differentiation, markers of adipogenesis like GLUT4, FABP4, LPL and PPARs, and of signaling pathways like AMPK/ACC2, JAK/STAT and MAPK were analyzed. Functional markers like adipokine secretion and triglyceride content as well as ROS production were measured in mature adipocytes. We found significantly lower expression levels of adipogenic markers, a reduction in lipid accumulation, higher leptin- and reduced adiponectin levels in the supernatant of treated adipocytes. Moreover, ROS production was significantly elevated after DEHP-exposure. In conclusion, DEHP led to lower grade of adipogenic differentiation in human SGBS-adipocytes under the chosen conditions.

Topics: Adipocytes; Adipogenesis; Adiponectin; Arrhythmias, Cardiac; Cells, Cultured; Diethylhexyl Phthalate; Fatty Acids; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Intellectual Disability; Leptin; Plasticizers; Reactive Oxygen Species; Triglycerides

Adipokines play a central role in the development of diseases associated with insulin resistance and obesity. Hypoxia in adipose tissue leads to a dysregulation of the expression of adipokines. The effect of hypoxia on the more recently identified adipokine apelin in human adipocytes is unclear. Therefore, we aimed at investigating the role of hypoxia on the expression of the adipokine apelin. Differentiated human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were cultured under hypoxic conditions for varying time periods. A modular incubator chamber was used to create a hypoxic tissue culture environment (defined as 1% O(2), 94% N, and 5% CO(2)). In addition, hypoxic conditions were mimicked by using CoCl(2). The effect of hypoxia on the expression of the investigated adipokines was measured by real-time PCR and the secretion of apelin was quantified by ELISA. Induction of hypoxia significantly induced mRNA expression of leptin and apelin in differentiated SGBS adipocytes compared with the normoxic control condition. Expression of adiponectin was significantly decreased by hypoxia. In addition, the amount of secreted apelin protein in response to hypoxia was elevated compared to untreated cells. Furthermore, we could demonstrate that the observed hypoxia-induced induction of apelin mRNA expression is in the first phase dependent on HIF-1α. In our study, we could demonstrate for the first time that apelin expression and secretion by human adipocytes are strongly induced under hypoxic conditions and that the early response on hypoxia with apelin induction is dependent on HIF-1α.

Topics: Adipocytes; Adiponectin; Apelin; Arrhythmias, Cardiac; Cell Differentiation; Cell Hypoxia; Gene Expression Regulation; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoblotting; Intellectual Disability; Intercellular Signaling Peptides and Proteins; Leptin; RNA, Messenger