运动对老年肥胖大鼠脂联素的影响

目的：探讨运动对老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达、血浆脂联素浓度及胰岛素抵抗的影响。方法：取雄性SD大鼠,鼠龄21 d,分青春期、壮年期和老年期三个阶段喂养高脂饲料（脂肪率为36.3%~40.0%）,建立老年肥胖模型。鼠龄达到60周后,取自然生长老年大鼠随机分为对照组（C）和老年运动组（AE）,n=6;取老年肥胖大鼠随机分为肥胖对照组（OC）和肥胖运动组（OE）,n=6。动物跑台坡度0°,运动速度及时间为（15 m/min×15 min）,4组/次,组间休息5 min,每次共运动60 min,5次/周,持续运动8周。8周后,检测内脏脂肪组织脂联素mRNA和蛋白质表达,测定血糖、血浆脂联素浓度和胰岛素浓度,计算胰岛素抵抗。结果：运动干预后,与对照组比较,肥胖对照组大鼠脂联素mRNA和蛋白质表达显著减低,血糖浓度和胰岛素抵抗明显增高;而老年运动组大鼠脂联素mRNA和蛋白质表达显著增高。与肥胖对照组大鼠比较,肥胖运动组大鼠脂联素mRNA和蛋白质表达显著增高、血浆脂联素水平增高,血糖浓度和胰岛素抵抗明显减低。结论：老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达均降低,伴随胰岛素抵抗、血糖升高。运动能显著增加其内脏脂肪组织脂联素mRNA和蛋白质表达,升高血浆脂联素水平,改善胰岛素抵抗,降低血糖。     

Impact of adiponectin gene polymorphisms on plasma lipoprotein and adiponectin concentrations of viscerally obese men

The aim of this study was first to examine the relationships between adiponectin gene (Apm1) polymorphisms and anthropometric indices as well as plasma adiponectin and lipoprotein/lipid levels, and then to investigate whether the presence of visceral obesity or insulin resistance may modulate the impact of these polymorphisms on metabolic risk variables. Molecular screening of the Apm1 gene was achieved, and a sample of 270 unrelated men recruited from the greater Quebec City area and selected to cover a wide range of body fatness values was genotyped. Sequencing of the Apm1 gene revealed two previously reported polymorphisms (c.45T>G and c.276G>T) as well as two newly identified genetic variations (-13752delT and -13702G>C). Carriers of the c.276T allele had higher LDL-cholesterol and lower HDL-triglyceride concentrations than did 276G/G homozygotes (P=0.02 and P=0.01, respectively). Carriers of the c.45G allele exhibited higher plasma adiponectin concentrations than did 45T/T homozygotes (P=0.04). After dividing each genotype group into subgroups for visceral AT, homozygotes for the normal allele at position -13752delT, carriers of the c.45G allele, and carriers of the c.276T allele had similar total apolipoprotein B (apoB) concentrations, whether they were viscerally obese or not. These results suggest that some Apm1 gene polymorphisms influence plasma adiponectin concentrations and lipoprotein/lipid levels. In addition, the impact of these polymorphisms is modulated by the presence of visceral obesity.     

Serum transaminases concentrations in obese children and adolescents

The aim of the study was to investigate the relationship between liver transaminase levels and metabolic syndrome (MS) features in obese children and adolescents. A total of 132 children and adolescents (73 males and 59 females) aged 8–16, participated in the study. All were studied at the department of Paediatrics, University Hospital of Zaragoza (Spain). Inclusion criteria were the existence of obesity as defined by body mass index (BMI) according to Cole cut-off values (when BMI was higher than the age and sex specific equivalent to 30 kg/m²). The definition of metabolic syndrome was according to the International Diabetes Federation criteria. Weight (kg), height (cm), waist circumference (cm), blood pressure and BMI were measured. Laboratory determinations after overnight fasting included: transaminases (ALT, AST, GGT), fasting glucose, insulin, triglycerides and HDL-C. The MS was found in 21.6% of the obese children and adolescents and the prevalence was higher in males (25.9%) than in females (15.9%). Serum transaminases (ALT, AST and GGT) mean concentrations were higher in males than in females, and decreased during pubertal development. The obese children and adolescents with the MS did not show higher transaminases concentrations when compared with those without the MS. Some MS manifestations (mainly waist circumference) showed a correlation with ALT, although all transaminases values were normal according to adult references. Liver transaminases, a surrogate marker of NAFLD, did not show an early and consistent manifestation of abnormalities in the obese children and adolescents studied. In order to define the presence of the disease, it would be necessary to obtain aminotransferase reference standards for children and adolescents, considering pubertal stage and gender.     

Zinc nutritional status in obese children and adolescents

Studies in animals and humans have corroborated that zinc (Zn) metabolism is altered in obesity. The present work intends to evaluate the Zn nutritional status in obese children and adolescents by the determination of some biochemical parameters and analyses of the diets. The investigation was carried out in a group of obese children and adolescents (n=23) and compared to a control group (n=21), both between 7 and 14 yr of age. A software analyzed diet information from 3-d food records. Body composition was evaluated by body mass index, bioelectrical impedance, and skinfold measurements. Zinc nutritional status was evaluated by Zn determination in plasma, erythrocyte, and 24-h urine, by atomic absorption spectrophotometry (γ=213.9 nm). Diets consumed by both groups had marginal concentrations of zinc. Zinc concentrations in plasma and erythrocytes were significantly lower in the obese group. Urinary zinc excretion was significantly higher in the same group. The results allowed one to conclude that zinc nutritional status in obese individuals is altered.     

Differential regulation of adiponectin receptor gene expression by adiponectin and leptin in myotubes derived from obese and diabetic individuals

Objective: This study aimed to investigate the regulation of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) gene expression in primary skeletal muscle myotubes, derived from human donors, after exposure to globular adiponectin (gAd) and leptin. Research Methods and Procedures: Four distinct primary cell culture groups were established [Lean, Obese, Diabetic, Weight Loss (Wt Loss); n = 7 in each] from rectus abdominus muscle biopsies obtained from surgical patients. Differentiated myotube cultures were exposed to gAd (0.1 μg/mL) or leptin (2.5 μg/mL) for 6 hours. AdipoR1 and AdipoR2 gene expression was measured by real‐time polymerase chain reaction analysis. Results: AdipoR1 mRNA expression in skeletal muscle myotubes derived from Lean subjects (p < 0.05) was stimulated 1.8‐fold and 2.5‐fold with gAd and leptin, respectively. No increase in AdipoR1 gene expression was measured in myotubes derived from Obese, Diabetic, or Wt Loss subjects. AdipoR2 mRNA expression was unaltered after gAd and leptin exposure in all myotube groups. Discussion: Adiponectin and leptin are rapid and potent stimulators of AdipoR1 in myotubes derived from lean healthy individuals. This effect was abolished in myotubes derived from obese, obese diabetic subjects, and obese‐prone individuals who had lost significant weight after bariatric surgery. The incapacity of skeletal muscle of obese and diabetic individuals to respond to exogenous adiponectin and leptin may be further suppressed as a result of impaired regulation of the AdipoR1 gene.     

High-molecular weight adiponectin isoforms increase after biliopancreatic diversion in obese subjects

Objective: Our objective was to test the effect of biliopancreatic diversion (BDP) in adiponectin multimerization. Adiponectin, the major protein secreted by adipose tissue, circulates in plasma in different isoforms. The most clinically relevant oligomers are high‐molecular weight (HMW) multimers and low‐molecular weight (LMW) trimers. Contrasting data on the effect of weight loss on adiponectin isoforms have been reported. Research Methods and Procedures: We measured total plasma adiponectin and HMW and LMW adiponectin oligomers (by Western blot analysis) before and 1 month after BPD, in 18 severely obese subjects. Results: One month after BPD, body weight decreased ～11%. Total adiponectin showed significant increase after BPD. In addition, we found a significant increase in HMW (percentage) adiponectin oligomers. We found a significant inverse correlation between HMW (percentage) and BMI before and after BPD. Homeostasis model of assessment‐insulin resistance decreased significantly after the BPD, without any significant correlation with total serum adiponectin and adiponectin oligomers. Discussion: A moderate weight loss after BPD increases total and HMW adiponectin oligomers. The significant correlation between BMI and HMW (percentage) adiponectin oligomers but not between BMI and total adiponectin might indicate a role of body fat mass in regulation of adiponectin multimerization. These data suggest that HMW oligomers represent a very sensitive parameter to short‐term BMI changes after BPD.     

Antiandrogenic contraceptives increase serum adiponectin in obese polycystic ovary syndrome patients

Increasing evidence suggests that adipocyte function is altered in the polycystic ovary syndrome (PCOS) as a result of androgen excess, providing an explanation for its frequent association with abdominal adiposity and insulin resistance. We here compared the response of serum adiponectin and leptin levels to the amelioration of androgen excess by means of treatment with an antiandrogenic oral contraceptive pill, as compared with the response to insulin sensitization with metformin. Thirty-four women presenting with PCOS were randomized to treatment with an oral contraceptive containing 35 microg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane(35) Diario) or with metformin (850 mg twice daily). Serum adiponectin and leptin levels were evaluated at baseline and after 12 and 24 weeks of treatment. In obese PCOS women, treatment with Diane(35) Diario resulted in an increase in serum adiponectin levels and in the adiponectin/leptin ratio, in parallel with a marked decrease in serum androgen concentrations, whereas no statistically significant changes were observed during treatment with metformin. On the contrary, leptin concentrations did not show any statistically significant change during the study with any of the drugs studied here. In summary, our present results might suggest a direct inhibitory effect of androgen excess on adiponectin secretion by adipocytes in obese PCOS women, supporting the hypothesis that androgen excess contributes to adipocyte dysfunction in these women.     

Abdominal fat and metabolic risk in obese children and adolescents

The aim of this study was to investigate fat distribution, mainly abdominal fat, and its relationship with metabolic risk variables in a group of 126 children and adolescents (60 males and 66 females) aged 5.0 to 14.9. According to IOTF criteria, 46 were classified as normal weight, 28 overweight and 52 obese. Weight, height, waist (WC) and hip circumferences were measured. The body mass index (BMI) was calculated. Total body fat, trunkal and abdominal fat were also assessed by dual energy x-ray absorptiometry (DXA). Glucose, insulin, HDL-Cholesterol, triglycerides (TG), ferritine, homocystein and C-reactive protein (CRP) were measured. Obesity status was related with insulin concentrations, CRP, TG and HDL. Obese patients had higher abdominal fat and higher CRP values than overweight and normal subjects. All markers of central body adiposity were related with insulin and lipid metabolism; however, they were not related with homocystein or ferritin. A simple anthropometric measurement, like waist circumference, seems to be a good predictor of the majority of the obesity related metabolic risk variables.     

Improved insulin sensitivity and adiponectin level after exercise training in obese Korean youth

Objective: The objective of this study was to investigate the association among adiposity, insulin resistance, and inflammatory markers [high‐sensitivity C‐reactive protein (hs‐CRP), interleukin (IL)‐6, and tumor necrosis factor (TNF)‐α] and adiponectin and to study the effects of exercise training on adiposity, insulin resistance, and inflammatory markers among obese male Korean adolescents. Research Methods and Procedures: Twenty‐six obese and 14 lean age‐matched male adolescents were studied. We divided the obese subjects into two groups: obese exercise group (N = 14) and obese control group (N = 12). The obese exercise group underwent 6 weeks of jump rope exercise training (40 min/d, 5 d/wk). Adiposity, insulin resistance, lipid profile, hs‐CRP, IL‐6, TNF‐α, and adiponectin were measured before and after the completion of exercise training. Results: The current study demonstrated higher insulin resistance, total cholesterol, LDL‐C levels, triglyceride, and inflammatory markers and lower adiponectin and HDL‐C in obese Korean male adolescents. Six weeks of increased physical activity improved body composition, insulin sensitivity, and adiponectin levels in obese Korean male adolescents without changes in TNF‐α, IL‐6, and hs‐CRP. Discussion: Obese Korean male adolescents showed reduced adiponectin levels and increased inflammatory cytokines. Six weeks of jump rope exercise improved triglyceride and insulin sensitivity and increased adiponectin levels.     

Exercise improves adiponectin concentrations irrespective of the adiponectin gene polymorphisms SNP45 and the SNP276 in obese Korean women

The effects of exercise on adiponectin levels have been reported to be variable and may be attributable to an interaction between environmental and genetic factors. The single nucleotide polymorphisms (SNP) 45 (T > G) and SNP276 (G > T) of the adiponectin gene are associated with metabolic risk factors including adiponectin levels. We examined whether SNP45 and SNP276 would differentially influence the effect of exercise training in middle-aged women with uncomplicated obesity. We conducted a prospective study in the general community that included 90 Korean women (age 47.0 ± 5.1 years) with uncomplicated obesity. The intervention was aerobic exercise training for 3 months. Body composition, adiponectin levels, and other metabolic risk factors were measured. Prior to exercise training, only body weight differed among the SNP276 genotypes. Exercise training improved body composition, systolic blood pressure, maximal oxygen consumption, high-density lipoprotein cholesterol, and leptin levels. In addition, exercise improved adiponectin levels irrespective of weight gain or loss. However, after adjustments for age, BMI, body fat (%), and waist circumference, no differences were found in obesity-related characteristics (e.g., adiponectin) following exercise training among the SNP45 and the 276 genotypes. Our findings suggest that aerobic exercise affects adiponectin levels regardless of weight loss and this effect would not be influenced by SNP45 and SNP276 in the adiponectin gene.     

Weight reduction in obese adolescents with and without binge eating

Little is known about binge eating (BE) in adolescents. The primary aim of the present study was to examine the relationship between BE and weight loss in adolescents (BMI ≥95th percentile) enrolled in a randomized controlled trial of behavioral and pharmacologic treatment of obesity. Participants were 82 treatment-seeking adolescents (BMI = 37.9 ± 3.8 kg/m(2); age = 14.1 ± 1.2 years; 67% females; 42% African American, 55% white). Participants completed the Children's Depression Inventory (CDI), the Piers Harris Self-Esteem Questionnaire, and the Eating Inventory (including cognitive restraint, disinhibition, and hunger scales). BE was assessed by a questionnaire and a confirmatory interview. At baseline, 24% of participants met criteria for BE (N = 13 met full BE disorder (BED) criteria; N = 7 met subthreshold BE). There were no significant differences in percentage reduction in initial BMI between participants with or without BE at month 6 (-7.0 ± 1.6 vs. -6.9 ± 0.9%) or month 12 (-8.8 ± 2.4 vs. -8.3 ± 1.3%) (omnibus main effect BE P = 0.89, interaction BE × time P = 0.84, interaction BE × drug P = 0.61). The rate of BE declined significantly over time from 24% (n = 20) at baseline to 8% (n = 6) at month 6 and 3% (n = 2) at month 12 (P = 0.003). There were significant decreases in hunger and disinhibition as well as an increase in cognitive restraint over time (all P ≤ 0.0001). Findings suggest a combination of behavioral and pharmacologic therapy may produce both weight loss and improvement in BE.     

Assessment of copper and lipid profile in obese children and adolescents

The aim of this study was to assess erythrocyte and plasma copper concentrations and correlate them with the lipid profile of overweight and obese children and adolescents. The study was performed with 15 over-weight and 30 obese children and adolescents, and the results were compared to the control group (21), aged 6–16 yr. Anthropometric assessment was carried out using body mass index (BMI). Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride serum levels were investigated. Erythrocyte and plasma copper levels were determined by atomic absorption spectrophotometry. Greater alterations in the lipid profile were observed in HDL-cholesterol, LDL-cholesterol, and triglyceride levels, with distinctions according to gender. The plasma copper concentrations in the overweight and obese male groups were significantly higher than those in the control group (p=0.0006). Negative correlations between plasma copper and total cholesterol (r=−0.54) and LDL cholesterol (r=−0.59) were observed in the obese male group. There was no statistical difference in copper erythrocyte concentrations. The obesity associated to disorders in lipid metabolism predisposes to changes in copper plasma concentrations, but there was no alteration in intracellular reserves, which suggests an important homeostatic control to compensate for plasma oscillations and metabolic alterations of the disease.     

Insulin resistance and impaired glucose tolerance in obese children and adolescents

In developed countries, obesity prevalence has strongly increased in the last decades. This has also been observed in children and adolescents. Until recently, type 2 diabetes mellitus was considered very rare among children and adolescents; however, in the last decades, some cases have been observed mainly in obese adolescents of some minority populations. The aim of our study was to assess the prevalence of type 2 diabetes, impaired glucose tolerance (IGT) and insulin resistance, and the metabolic features, in obese children and adolescents. We have studied 95 obese children and adolescents, 53 males and 42 females, aged 4-16 years. The prevalence of IGT in obese children and adolescents studied was 7.4%; there was not any child with type 2 diabetes. Fasting glucose and insulin serum concentrations did not show significant differences between obese children with or without IGT; however, 120 minutes after an oral glucose tolerance test, glucose and insulin serum concentrations showed statistically significant differences between both groups. Insulin resistance is defined as a HOMA index higher than 4. The prevalence of insulin resistance in obese children studied was 35.8%. Trygliceride serum concentrations were higher and HDL-C serum concentrations were lower in obese children with IGT than in those without IGT, but the differences were not statistically significant. IGT and insulin resistance are frequent in obese children and adolescents; early treatment in obese children and adolescents with IGT constitutes a strategy of reversing progression to beta-cell failure and in preventing type 2 diabetes.     

Hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss

Leptin has emerged over the past decade as a key hormone not only in energy balance regulation but also in neuroendocrine and inflammatory processes. The aim of the present study was to evaluate whether hyperleptinemia deregulates neuropeptides during weight loss. A total of 86 post-pubertal obese adolescents (with or without hyperleptinemia) participated in one year of interdisciplinary weight loss therapy (clinical, nutritional, psychological and exercise-related). Adipokine and neuropeptide concentrations were measured by ELISA, visceral fat was measured by ultrasound and body composition was measured by pletismography. The hyperleptinemic patients presented a lower alpha-MSH concentration and higher NPY/AgRP ratio while the adiponectin/leptin (A/L) ratio was lower compared with the non-hyperleptinemic group. After therapy, significant improvements in BM, BMI, body fat mass, visceral and subcutaneous fat, HOMA-IR, QUICKI, total cholesterol and triglycerides were observed in both groups. Indeed, we observed significant increases in adiponectin and A/L as well as reductions in leptin and NPY/AgRP ratio in the hyperleptinemic group. In the stepwise multiple linear regression analysis with leptin concentration as the dependent variable, α-MSH and body fat mass (%) were the independent predictors to explain leptin concentration. For the entire group, we found positive correlations between leptinemia and BMI and body fat mass (%) as well as a negative correlation with free fat mass (%) and alpha-MSH. Finally, we verified negative correlations between adiponectin/leptin ratio with total cholesterol and LDL-c, only in hyperleptinemic patients. In conclusion, the hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss.     

Macrophage migration inhibitory factor is elevated in obese adolescents

Objectives: The prevalence of obesity in childhood and adolescence is continuing rising. Macrophage migration inhibitory factor (MIF) participates in inflammatory and immune responses as a pro-inflammatory cytokine. The present study aimed to investigate MIF in overweight adolescents. Methods: Seventy-nine male adolescents were enrolled. Thirty-eight were overweight according to the 90th%ile of the age-specific waist circumference. Various parameters were recorded at one visit, including body mass index. MIF was determined using multiplex immune-assay technology. Results: Overweight adolescents had increased systolic blood pressure and CRP levels. Furthermore, increased circulating MIF concentrations were observed (Median: 964.6 pg/ml, Interquartile range: 590.3-2019.4 versus Median: 562.7 pg/ml, Interquartile range: 430.6-813.7, p = 0.003). Increased MIF concentrations were associated with increased markers of inflammation and obesity. Conclusions: We demonstrated elevated MIF levels in obese adolescents. Taken together with other markers, this indicates the presence of low-grade inflammation in these young subjects, possibly representing a link between obesity and related co-morbidities.     

Effects of physical exercise on butyrylcholinesterase in obese adolescents

The aim of the present study was to evaluate the effect of a 12 week program of physical exercise (PE) on butyrylcholinesterase (BChE) in obese adolescents. This study compared obese adolescents (N = 54) before and after PE, regarding the relative intensity (RI) and activity of different molecular forms (G1, G2, G4 and G1-ALB) of BChE found in plasma. Waist circumference (WC) and lipid profile were also assessed before and after PE. It was shown that before PE, mean plasma BChE activity was significantly higher in obese than in non-obese adolescents and that it was significantly reduced after PE, becoming similar to that found in non-obese adolescents. Lipid profile and WC also changed in response to PE. These results are consistent with studies that found a correlation between BChE and lipid metabolism and suggest that PE may have led to a physiological regularization of plasma BChE activity. Although mean BChE activity of each isoform was significantly reduced by PE, their RI did not change. This is in accordance with a previous suggestion that this proportion is maintained under factors such as obesity, and may therefore be important for BChE functions.