Leptin increases prostate cancer aggressiveness

Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.     

Some essential elements in maternal and cord blood in relation to birth weight and gestational age of the baby

Maternal and cord blood were collected from 54 Indian women at parturition and analyzed for Zn, Cu, and Fe by flame atomic absorption spectrophotometry to determine the relationship between levels of these elements in mother’s and infant’s blood and maternal age, birth weight, and gestational age of the baby. The blood Zn level of mothers in the age group 24–28 yr was significantly higher than those of mothers in the age group of 18–23 yr (p<0.05). Similarly, mothers in the 24 to 28-yr group also had higher blood Fe level than mothers in the group 29–38 yr (p<0.05). The levels of Zn, Cu, and Fe were higher in the maternal blood and lower, but not significantly, in the cord blood of low-birth-weight babies than in those of normal-birth-weight babies. However, differences in the levels of Zn, Cu, and Fe between maternal and cord blood of the two birth-weight groups was statistically significant. There were no significant differences in the levels of the three elements in maternal or cord blood by the gestational age of the baby. A weak but significant correlation was found between the birth weight of the baby and the Fe level in the cord blood (r=0.26; p<0.05). Also, weak significant correlations were observed between gestational age of the baby and Fe (r=0.23; p<0.05) and Cu (r=0.31; p<0.05) levels in the cord blood. Although, there are many confounders of low birth weight and preterm deliveries, a diminished placental transfer of these essential elements could be one of the several etiological factors for low birth weight of newborns.     

Adolescent Sex Differences in Adiponectin Are Conditional on Pubertal Development and Adiposity

Objective: Adiponectin is an adipose tissue protein with important insulin‐sensitizing, anti‐inflammatory, and cardioprotective properties but is paradoxically lower in obese individuals. Sex differences in adiponectin have been reported in adults and adolescents but not in prepubertal children. In this study, we hypothesized that sex differences in adiponectin would develop during puberty and would be influenced by level of adiposity. Research Methods and Procedures: Adiponectin levels were measured in 1196 white and African‐American adolescents. Insulin resistance was estimated using the homeostasis model (HOMA‐IR). Demographic, developmental, and metabolic variables, including interactions with adiposity measurements, were evaluated for independent relationships with adiponectin levels. Results: Overall, adiponectin levels varied significantly by sex, race, adiposity, and puberty stage. Significant sex differences in adiponectin developed after the onset of puberty, particularly in lean adolescents. Adolescent boys had lower adiponectin levels in post‐puberty compared with pre‐puberty (p = 0.01) and had lower levels than girls in both puberty and post‐puberty (both p < 0.001), after adjusting for race, BMI z‐score, and natural logarithm‐(HOMA‐IR). Sex differences were also conditional on adiposity level, with significant sex differences among lean (p < 0.001) but not among non‐lean (p = 0.16) adolescents. Adiponectin levels in girls decreased more with increasing adiposity than in boys (p = 0.004), but only marginally so after standardizing for girls’ higher mean adiponectin level (p = 0.11). Discussion: Sex differences in adiponectin are dependent on both puberty stage and adiposity in adolescents, such that by post‐puberty, non‐lean boys exhibit the lowest levels of adiponectin.     

Relationship of Serum Adiponectin and Leptin Concentrations with Body Fat Distribution in Humans

Objective: We investigated whether serum concentrations of adiponectin are determined by body fat distribution and compared the findings with leptin. Research Methods and Procedures: Serum concentrations of adiponectin and leptin were measured by radioimmunoassay (n = 394) and analyzed for correlation with sex, age, and body fat distribution, i.e., waist‐to‐hip ratio, waist and hip circumference, and subcutaneous adipose tissue area of the lower leg as assessed by magnetic resonance imaging. Results: After adjusting for sex and percentage of body fat, adiponectin was negatively (r = ?0.17, p < 0.001) and leptin was positively (r = 0.22, p < 0.001) correlated with waist‐to‐hip ratio. Leptin, but not adiponectin, correlated with both waist (r = 0.49, p < 0.001) and hip circumference (r = 0.46, p < 0.001). Furthermore, leptin, but not adiponectin, correlated with the proportion of subcutaneous fat of the lower leg cross‐sectional area (r = 0.37, p < 0.001). Discussion: These data suggest that both adipocytokines are associated with central body fat distribution, and serum adiponectin concentrations are determined predominantly by the visceral fat compartment.     

Extension of coronary artery disease is associated with increased IL-6 and decreased adiponectin gene expression in epicardial adipose tissue

Epicardial adipose tissue (EAT) expresses lower levels of adiponectin in patients with CAD and higher levels of inflammatory mediators such as IL-6 and leptin than subcutaneous adipose tissue. This showed one important role of EAT in coronary artery disease. However, the relationship of EAT adiponectin and IL-6 levels to the extension of coronary artery disease has not hitherto been determined. We sought to determine whether the levels of adiponectin and interleukin-6 (IL-6) mRNA in epicardial adipose tissue are associated with the extension of coronary artery disease (CAD). Methods: Angiographic and hormones expression were evaluated from epicardial and subcutaneous adipose tissue. 92 patients (58 CAD, 34 non-CAD) who underwent cardiac surgery. Adiponectin and IL-6 mRNA levels were measured by real time RT-PCR in epicardial and subcutaneous adipose tissue (SAT) following angiographic evaluation of their coronary arteries. Results: We found that epicardial adipose tissue of CAD expressed lower levels of adiponectin mRNA and higher levels of IL-6 mRNA than that of non-CAD patients. As the number of injured arteries rose, adiponectin mRNA levels decreased (r = −0.402, p < 0.001) and IL-6 mRNA increased (r = 0.514, p < 0.001) in epicardial adipose tissue. Conclusions: The extension of CAD is significantly associated with the expression of adiponectin and IL-6 mRNA in EAT. These findings suggest that low adiponectin and high IL-6 expression by EAT may contribute to CAD extension.     

Effect of Lifestyle Modification on Adipokine Levels in Obese Subjects with Insulin Resistance

Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty‐four insulin‐resistant obese subjects with varying degrees of glucose tolerance completed a 6‐month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)] and highly sensitive C‐reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 ± 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 ± 3 vs. 23.6 ± 3 ng/mL, p = 0.01) and IL‐6 (2.75 ± 1.51 vs. 2.3 ± 0.91 pg/mL, p = 0.012). TNF‐α levels tended to decrease (2.3 ± 0.2 vs. 1.9 ± 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C‐reactive protein (r = 0.466, p < 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL‐6 and a tendency toward a decrease in circulating TNF‐α, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.     

Maternal and fetal leptin,adiponectin levels and associations with fetal insulin sensitivity

Objective:

It remains uncertain whether leptin and adiponectin levels are correlated in maternal vs. fetal circulations. Little is known about whether leptin and adiponectin affect insulin sensitivity during fetal life.

Design and Methods:

In a prospective singleton pregnancy cohort (n = 248), we investigated leptin and adiponectin concentrations in maternal (at 24‐28 and 32‐35 weeks of gestation) and fetal circulations, and their associations with fetal insulin sensitivity (glucose/insulin ratio, proinsulin level).

Results:

Comparing concentrations in cord vs. maternal blood, leptin levels were 50% lower, but adiponectin levels more than doubled. Adjusting for gestational age at blood sampling, consistent and similar positive correlations (correlation coefficients: 0.31‐0.34, all P < 0.0001) were observed in leptin or adiponectin levels in maternal (at 24‐28 or 32‐25 weeks of gestation) vs. fetal circulations. For each SD increase in maternal plasma concentration at 24‐28 weeks, cord plasma concentration increased by 12.7 (95% confidence interval 6.8‐18.5) ng/ml for leptin, and 2.9 (1.8‐4.0) µg/ml for adiponectin, respectively (adjusted P < 0.0001). Fetal insulin sensitivity was negatively associated with cord blood leptin (each SD increase was associated with a 5.4 (2.1‐8.7) mg/dl/µU/ml reduction in cord plasma glucose/insulin ratio, and a 5.6 (3.9, 7.4) pmol/l increase in proinsulin level, all adjusted P < 0.01) but not adiponectin (P > 0.4) levels). Similar associations were observed in nondiabetic full‐term pregnancies (n = 211).

Conclusions:

The results consistently suggest a maternal impact on fetal leptin and adiponectin levels, which may be an early life pathway in maternal‐fetal transmission of the propensity to obesity and insulin resistance.     

In Utero Gender Dimorphism of Adiponectin Reflects Insulin Sensitivity and Adiposity of the Fetus

Circulating adiponectin reflects the degree of energy homeostasis and insulin sensitivity of adult individuals. Low abundance of the high molecular weight (HMW) multimers, the most active forms mediating the insulin‐sensitizing effects of adiponectin, is indicative of impaired metabolic status. The increase in fetal adiponectin HMW compared with adults is a distinctive features of human neonates. To further understand the functional properties of adiponectin during fetal life, we have evaluated the associations of adiponectin with insulin sensitivity, body composition, and gender. Umbilical cord adiponectin, adiponectin complexes, and metabolic parameters were measured at term by elective cesarean delivery. The associations between adiponectin, measures of body composition, and insulin sensitivity were evaluated in relation to fetal gender in 121 singleton neonates. Higher total adiponectin concentrations in female compared with male fetuses (34.3 ± 9.5 vs. 24.9 ± 8.6, P < 0.001) were associated with a 3.2‐fold greater abundance in circulating HMW complexes (0.20 ± 0.03 vs. 0.08 ± 0.03, P < 0.001, n = 9). Adiponectin was positively correlated with neonatal fat mass (r = 0.27, P < 0.04) and percent body fat in female fetuses (r = 0.28, P < 0.03) and with lean mass in males (r = 0.28, P < 0.03). There was no significant correlation between cord adiponectin and fasting insulin concentrations or fetal insulin sensitivity as estimated by homeostasis model assessment of insulin resistance (HOMA‐IR). The gender dimorphism for plasma adiponectin concentration and complex distribution first appears in utero. In sharp contrast to the inverse correlation found in adults, the positive relationship between adiponectin and body fat is a specific feature of the fetus.     

Serum zinc levels of cord blood: Relation to birth weight and gestational period

BackgroundZn-deficiency has been associated with numerous alterations during pregnancy including low birth weight; however, the research relating neonatal zinc status and birth weight has not produced reliable results.ObjectiveTo compare the serum Zn-levels of cord blood in healthy newborns and low birth weight newborns, and to assess a possible relationship between zinc concentration and neonatal birth weight and gestational age.Material and methods123 newborns divided in “study group” (n = 50) with <2500 g birth weight neonates and “control group” (n = 73) with ≥2500 g birth weight neonates were enrolled. Study group was subdivided according to gestational age in preterm (<37 weeks) and full-term (≥37 weeks). Serum cord blood samples were collected and the Zn-levels were analyzed using flame Atomic Absorption Spectrophotometry method and the result was expressed in μmol/L. The Zn-levels were compared between the groups (Mann–Whitney-U test) and the Zn-levels were correlated with the birth weight and gestational age (Spearman's rank correlations).ResultsStatistically significant low positive correlation between Zn-levels and birth weight (ρ = 0.283; p = 0.005) was found. No statistically significant difference between Zn-levels of study and control groups [17.00 ± 0.43 vs. 18.16 ± 0.32 (p = 0.053)] was found. Statistically significant low positive correlation between Zn-levels and gestational age (ρ = 0.351; p = 0.001) was found. No statistically significant difference between Zn-levels of preterm as compare to full-term newborns [16.33 ± 0.42 vs. 18.43 ± 0.93 (p = 0.079)] was found. Zn-level of preterm subgroup was significantly lower compared to control group (p = 0.001).ConclusionsDespite low birth weight preterm neonates had significantly lower serum zinc levels of cord blood than healthy term neonates, the correlation between cord blood zinc levels and birth weight and gestational age was lower. The results are not enough to relate the change in cord blood zinc concentration to the birth weight values or gestational period. In relation to complicated pregnancies, further studies regarding zinc levels in blood in our population are required.     

Resistin,Adiponectin, Ghrelin,Leptin, and Proinflammatory Cytokines: Relationships in Obesity

Objective: To evaluate interactions among leptin, adiponectin, resistin, ghrelin, and proinflammatory cytokines [tumor necrosis factor receptors (TNFRs), interleukin‐6 (IL‐6)] in nonmorbid and morbid obesity. Research Methods and Procedures: We measured these hormones by immunoenzyme or radiometric assays in 117 nonmorbid and 57 morbidly obese patients, and in a subgroup of 34 morbidly obese patients before and 6 months after gastric bypass surgery. Insulin resistance by homeostasis model assessment, lipid profile, and anthropometrical measurements were also performed in all patients. Results: Average plasma lipids in morbidly obese patients were elevated. IL‐6, leptin, adiponectin, and resistin were increased and ghrelin was decreased in morbidly obese compared with nonmorbidly obese subjects. After adjusting for age, gender, and BMI in nonmorbidly obese, adiponectin was positively associated with HDLc and gender and negatively with weight (β = ?0.38, p < 0.001). Leptin and resistin correlated positively with soluble tumor necrosis factor receptor (sTNFR) 1 (β = 0.24, p = 0.01 and β = 0.28, p = 0.007). In the morbidly obese patients, resistin and ghrelin were positively associated with sTNFR2 (β = 0.39, p = 0.008 and β = 0.39, p = 0.01). In the surgically treated morbidly obese group, body weight decreased significantly and was best predicted by resistin concentrations before surgery (β = 0.45, p = 0.024). Plasma lipids, insulin resistance, leptin, sTNFR1, and IL‐6 decreased and adiponectin and ghrelin increased significantly. Insulin resistance improved after weight loss and correlated with high adiponectin levels. Discussion: TNFα receptors were involved in the regulatory endocrine system of body adiposity independently of leptin and resistin axis in nonmorbidly obese patients. Our results suggest coordinated roles of adiponectin, resistin, and ghrelin in the modulation of the obesity proinflammatory environment and that resistin levels before surgery treatment are predictive of the extent of weight loss after bypass surgery.     

Maternal Smoking and Metabolic Health Biomarkers in Newborns

Background

Maternal smoking has been associated with elevated risk of type 2 diabetes among the offspring in adulthood. The mechanisms underlying this fetal “programming” effect remain unclear. The present study sought to explore whether maternal smoking affects metabolic health biomarkers in fetuses/newborns.

Methods

In a prospective singleton pregnancy cohort (n = 248), we compared metabolic health biomarkers in the newborns of smoking and non-smoking mothers. Outcomes included cord plasma insulin, proinsulin, insulin-like growth factor I (IGF-I), IGF-II, leptin and adiponectin concentrations, glucose-to-insulin ratio (an indicator of insulin sensitivity) and proinsulin-to-insulin ratio (an indicator of β-cell function).

Results

Independent of maternal (glucose tolerance, age, ethnicity, parity, education, body mass index, alcohol use) and infant (sex, gestational age, birth weight z score, mode of delivery, cord blood glucose concentration) characteristics, the newborns of smoking mothers had lower IGF-I concentrations (mean: 6.7 vs. 8.4 nmol/L, adjusted p = 0.006), and marginally higher proinsulin-to-insulin ratios (0.94 vs. 0.72, adjusted p = 0.06) than the newborns of non-smoking mothers. Cord plasma insulin, proinsulin, IGF-II, leptin and adiponectin concentrations and glucose-to-insulin ratios were similar in the newborns of smoking and non-smoking mothers.

Conclusions

Maternal smoking was associated with decreased fetal IGF-I levels, and borderline lower fetal β-cell function. Larger cohort studies are required to confirm the latter finding. The preliminary findings prompt the hypothesis that these early life metabolic changes may be involved in the impact of maternal smoking on future risk of metabolic syndrome related disorders in the offspring.     

Leptin Responses to Weight Loss in Postmenopausal Women: Relationship to Sex‐Hormone Binding Globulin and Visceral Obesity

Objective: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women. Research Methods and Procedures: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone‐binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0 ± 4.5 kg/m²; mean ± SD), women (60 ± 6 years) before and after a 6‐month hypocaloric diet (250 to 350 kcal/day deficit). Results: Body weight decreased by 5.8 ± 3.4 kg (7.1%) and leptin levels decreased by 6.6 ± 11.9 ng/mL (14.5%) after the 6‐month treatment. Insulin levels decreased 10% (p < 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p < 0.0001), fat mass (r = 0.38, p < 0.01), subcutaneous fat area (r = 0.52, p < 0.0001), and with baseline values of SHBG (r = 0.38, p < 0.01) and baseline intra‐abdominal fat area (r = ?0.27, p < 0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r² = 0.24, p < 0.01), relative changes in body weight (cumulative r² = 0.40, p < 0.05), and baseline intra‐abdominal fat area (cumulative r² = 0.48, p < 0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance. Discussion: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.     

Plasma Levels of Adiponectin,a Novel Adipocyte‐Derived Hormone,in Sleep Apnea**

Objective: Obstructive sleep apnea (OSA) is associated with obesity, sympathetic activation, systemic inflammation, and cardiovascular morbidity. Obesity, β‐adrenergic agonists, and inflammation are linked to decreased expression and/or secretion of an adipose tissue‐derived antiatherogenic hormone, adiponectin. The purpose of the study was to investigate whether OSA affected plasma levels of adiponectin, which might help explain OSA‐associated cardiovascular morbidity. Research Methods and Procedures: We randomly selected 68 otherwise healthy male subjects, either with moderate/severe OSA [apnea‐hypopnea index (AHI) ≥ 20; n = 35] or without OSA (AHI ≤ 5; n = 33). The diagnosis of OSA was made based on prospective full polysomnography. Adiponectin was measured before polysomnography between 8 and 10 PM . Results: AHI was higher in the OSA group (49.5 ± 4.4 vs. 2.9 ± 0.4 events/h; p < 0.001). OSA subjects were also more obese, with greater BMI (33 ± 1 vs. 30 ± 1; p = 0.016) and percentage body fat (29 ± 1% vs. 26 ± 1%; p = 0.030). Adiponectin levels were 7.67 ± 0.73 and 6.33 ± 0.51 μg/mL in the OSA and non‐OSA groups, respectively, and this difference was significant in covariate analysis (taking into account age, hemodynamic characteristics, measures of body fat, and OSA severity) (p = 0.009). After excluding from both groups the subjects with extreme BMI, such that the OSA and non‐OSA study cohorts had similar BMI and percentage body fat, subjects with OSA had significantly higher plasma adiponectin (8.49 ± 0.92 vs. 6.32 ± 0.55 μg/mL; p = 0.042), differences also evident in covariate analysis (p = 0.017). Discussion: Plasma adiponectin levels are elevated in otherwise healthy subjects with OSA. Therefore, low adiponectin is unlikely to explain the association between OSA and cardiovascular disease.     

Changes in body mass,serum leptin,and mRNA levels of leptin receptor isoforms during the premigratory period in <Emphasis Type="Italic">Myotis lucifugus</Emphasis>

Migration and hibernation in mammals may be preceded by a period of leptin resistance, which may in part account for the increasing adiposity and body mass that occurs during these periods. We hypothesized that hypothalamic expression of leptin receptor mRNA would decrease during the premigration (PM) period in the little brown myotis, Myotis lucifugus. Body mass of M. lucifugus increased during the PM period, but serum leptin levels did not change during that time. Hypothalamic mRNA levels for both the short (ObRa) and fully active long (ObRb) forms of the leptin receptor increased during PM, but the relative increase in ObRa was larger and occurred sooner than ObRb. mRNA levels of an inhibitor of leptin signaling (protein inhibitor of activated STAT3: PIAS3) increased in hypothalami during the PM period in bats. Adiponectin is an adipokine that has been linked to obesity in rodents; normally, serum levels of adiponectin decrease in obesity. In M. lucifugus, adiponectin mRNA levels decreased in adipose tissue during the period of mass gain, but circulating adiponectin levels did not change. We conclude that the relative changes in leptin receptor isoform expression during the PM fattening period may favor binding of leptin to the less active short isoform. Coupled with increased expression of PIAS3 and the dissociation of serum leptin levels from body mass and adiposity, these changes could account in part for the adaptive fattening during the PM period. In addition, the adipokine profiles of M. lucifugus during the PM period and that of obesity in non-hibernating mammals are strikingly dissimilar.     

Central leptin gene therapy blocks ovariectomy-induced adiposity

Objective: In this study, we tested the hypothesis that insufficiency of leptin restraint in the hypothalamus is responsible for promoting weight gain and adiposity after ovariectomy (ovx). Whether increasing leptin transgene expression can overcome the diminution in leptin restraint was evaluated in ovx rats. Research Methods and Procedures: Enhanced leptin or green fluorescent protein (GFP; control) transgene expression was induced by a single intracerebroventricular injection of recombinant adeno‐associated viral vector encoding either leptin gene (rAAV‐lep) or GFP gene (rAAV‐GFP; control) in acutely and chronically ovx rats. Body weight and food intake responses were monitored weekly. White adipose tissue (WAT) mass and serum levels of WAT‐derived hormones, leptin, and adiponectin were analyzed at termination of the experiments. Results and Discussion: An increase in leptin transgene expression in the hypothalamus initiated soon after ovx blocked hyperphagia and body weight gain and markedly suppressed WAT mass and adipokines, leptin, and adiponectin. Similar suppression of weight gain and adiposity and serum leptin and adiponectin levels after intracerebroventricular rAAV‐lep injection in chronically ovx rats were observed concomitant with unchanged daily food intake. These findings are consistent with the hypothesis that in the absence of ovarian steroids, the existent insufficiency of leptin restraint at the hypothalamic level can be overcome with ectopic leptin expression, thereby reinstating central control on weight and adiposity.     

An SNP in the Adiponectin Gene Is Associated with Decreased Serum Adiponectin Levels and Risk for Impaired Glucose Tolerance

Adiponectin is a plasma protein produced by the adipose tissue. Hypoadiponectinemia has been associated with insulin resistance and several components of the metabolic syndrome (MS): type 2 diabetes, obesity, and dyslipidemia. We investigated whether single nucleotide polymorphisms (SNPs) at positions 45 and 276 in the adiponectin gene were associated with features of the MS in 747 unrelated Spanish subjects. The G allele of SNP45 and the G/G genotype of SNP276 were associated with impaired glucose tolerance (p = 0.020 and 0.042, respectively). The G/G genotype for SNP276 was associated with lower serum adiponectin levels as compared with the G/T and T/T genotypes (G/G, 10.10 ± 0.24 μg/mL; G/T, 10.98 ± 0.32 μg/mL; T/T, 12.00 ± 0.92 μg/mL; p = 0.015) even after adjustment for sex, age, BMI, waist‐to‐hip ratio, homeostasis model assessment index, and the degree of glucose tolerance (p = 0.040). We found a significant negative association of circulating adiponectin levels with waist‐to‐hip ratio (r = ?0.42, p < 0.001), sagittal abdominal diameter (r = ?0.24, p < 0.001), triglycerides (r = ?0.32, p < 0.001), homeostasis model assessment index (r = ?0.14, p = 0.001), and uric acid (r = ?0.36, p < 0.001) and positive association with high‐density lipoprotein‐cholesterol (r = 0.41, p < 0.001). Our findings indicate that serum adiponectin levels are associated with several components of the MS. The SNP276 of the adiponectin gene may affect impaired glucose tolerance and hypoadiponectinemia.     

Mitochondrial DNA depletion in small- and large-for-gestational-age newborns

Objective: To investigate whether mitochondrial DNA (mtDNA) content may be associated with clinical features, anthropometric variables, and laboratory findings in both extremes of abnormal fetal growth: small and large size for gestational age. Research Methods and Procedures: Eighty‐eight pregnant women and their infants were included in a cross‐sectional study. According to the offspring birthweight, normalized by sex and gestational age, there were 57 newborns with appropriate weight for gestational age (AGA) and 31 with abnormal weight for gestational age: 17 small for gestational age (SGA) and 14 large for gestational age (LGA). mtDNA quantification using nuclear DNA as a reference was measured by a real‐time quantitative polymerase chain reaction method. Results: The mothers’ pregestational BMI was associated with the weight of their offspring: SGA infants had lean mothers (BMI, 21.4 ± 0.7), and LGA infants had overweight mothers (BMI, 26.7 ± 1.4) in comparison with AGA infants (BMI, 23.0 ± 0.7) (p < 0.003). Newborn leptin levels were associated with birthweight after adjustment for sex and gestational age (SGA, 7.0 ± 1.1 ng/mL; AGA, 15.2 ± 1.6 ng/mL; and LGA, 25.6 ± 4.1 ng/mL) (p < 0.002). Conversely, mtDNA/nuclear DNA ratio was significantly lower in both extremes of abnormal fetal growth, SGA (18 ± 6) and LGA (9 ± 2), at birth in comparison to AGA‐weight infants (28 ± 4) (p < 0.03). Discussion: Our findings show that mtDNA content is decreased in newborns with abnormal weight in comparison with AGA infants. On the basis of a cumulative body of evidence, we speculate that mtDNA depletion is one of the putative links between abnormal fetal growth and metabolic and cardiovascular complications in later life.     

Plasma Leptin Response to an Epinephrine Infusion in Lean and Obese Women

Objective: Because leptin production by adipose tissue is under hormonal control, we examined the impact of epinephrine administration on plasma leptin concentrations. Research Methods and Procedures: We measured plasma leptin, insulin, and free fatty acid (FFA) responses after a 60-minute epinephrine infusion (0.010 μg/kg fat free mass/min) followed by a 30-minute recovery period (no infusion) in a group of 11 lean (mean body mass index ± SD: 22.6 ± 1.1 kg/m²) and 15 obese (30.0 ± 1.3 kg/m²) premenopausal women. Leptin, insulin, and FFA levels were measured in plasma before (−15 and 0 minutes) and at every 30 minutes over the 90-minute period. Results: In both lean and obese individuals, plasma leptin was significantly reduced by epinephrine (p < 0.0001). Body fat mass was associated with fasting leptin levels (r = 0.64, p < 0.0005) as well as with the decrease in leptinemia (r = −0.51, p < 0.01) produced by epinephrine administration. Furthermore, we noted a large range of leptin response to epinephrine among our subjects, especially in obese women (from −12 to −570 ng/mL per 60 minutes). However, there was no association between postepinephrine leptin and FFA levels (r = −0.14, p = 0.55). Discussion: Results of this study indicate that leptin levels decrease after epinephrine administration in both lean and obese premenopausal women. However, the heterogeneity in the response of leptin to catecholamines suggests potential alterations of the leptin axis that may contribute to generate a positive energy balance and, thus, may favor weight gain in some obese individuals.