Effect of a 12-Week Low vs. High Intensity Aerobic Exercise Training on Appetite-Regulating Hormones in Obese Adolescents: A Randomized Exercise Intervention Study.

Little is known about how the intensity of aerobic training influences appetite-regulating hormones in obese adolescents. Our goal was to assess the effect of low and high intensity aerobic trainings on food intake and appetite-regulating hormones in obese adolescents. Forty three obese adolescents (age: 13-18y, BMI: 34.48 ± 3.94 kg/m2) were randomized into high intensity training (HIT; n = 20) or low intensity training (LIT; n = 23) groups for 12 weeks. All participants also received the same nutritional, psychological and clinical counseling. Pre- and postintervention energy intake (EI) and circulating levels of insulin, leptin, peptide YY3-36 (PYY3-36) and ghrelin were measured. Adolescents in the HIT showed a reduction in total EI and an increase in PYY3-36 (p < .05). Aerobic exercise training performed at ventilatory threshold 1 intensity, reduced EI and augmented PYY3-36 in obese adolescents, compared with LIT. The data suggest that HIT and LIT have differential effects in the regulation of appetite signals and subsequent EI in obese adolescents.

A double-blind randomized trial of fish oil to lower triglycerides and improve cardiometabolic risk in adolescents.

OBJECTIVES: To determine the efficacy of 4 g/day fish oil to lower triglycerides and impact lipoprotein particles, inflammation, insulin resistance, coagulation, and thrombosis. STUDY DESIGN: Participants (n = 42, age 14 ± 2 years) with hypertriglyceridemia and low-density lipoprotein (LDL) cholesterol <160 mg/dL were enrolled in a randomized, double-blind, crossover trial comparing 4 g of fish oil daily with placebo. Treatment interval was 8 weeks with a 4-week washout. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, fibrinogen, plasminogen activator inhibitor-1, and thrombin generation were measured. RESULTS: Baseline lipid profile was total cholesterol 194 (5.4) mg/dL (mean [SE]), triglycerides 272 (21) mg/dL, high-density lipoprotein cholesterol 39 (1) mg/dL, and LDL cholesterol 112 (3.7) mg/dl. LDL particle number was 1614 (60) nmol/L, LDL size was 19.9 (1.4) nm, and large very low-density lipoprotein/chylomicron particle number was 9.6 (1.4) nmol/L. Triglycerides decreased on fish oil treatment but the difference was not significant compared with placebo (-52 ± 16 mg/dL vs -16 ± 16 mg/dL). Large very low-density lipoprotein particle number was reduced (-5.83 ± 1.29 nmol/L vs -0.96 ± 1.31 nmol/L; P < .0001). There was no change in LDL particle number or size. There was a trend towards a lower prothrombotic state (lower fibrinogen and plasminogen activator inhibitor-1; .10 > P > .05); no other group differences were seen. CONCLUSIONS: In children, fish oil (4 g/day) lowers triglycerides slightly and may have an antithrombotic effect but has no effect on LDL particles.

Obesity-related increased γ' fibrinogen concentration in children and its reduction by a physical activity-based lifestyle intervention: a randomized controlled study.

OBJECTIVE: To determine if elevated plasma γ'-fibrinogen, typically involved in the formation of fibrinolysis-resistant clots, confers an increased risk for cardiovascular disease (CVD) and thrombosis in children as it does in adults. Although obesity-related hyperfibrinogenemia is frequently reported in children, the role of γ' fibrinogen and its response to physical activity-based lifestyle are less clear in this population. STUDY DESIGN: In a randomized controlled 3-month physical activity-based lifestyle intervention, γ' fibrinogen concentration was measured in 21 children (aged 14-18 years; Tanner stage > IV), including 15 in the obese group and 6 in the normal weight group, with body mass index percentiles for age and sex of >95 and <85, respectively. RESULTS: The relationships between γ' fibrinogen and other risk factors for CVD, such as markers of insulin resistance and subclinical inflammation, along with body composition (as measured by dual-energy X-ray absortiometry), were assessed before and after the intervention. γ' fibrinogen concentration was higher in the obese group compared with the normal weight group (P < .05) and was correlated with other risk factors for CVD (adjusted R(2) = 0.9; P < .05), and insulin emerged as the major predictor of γ' fibrinogen. The intervention reduced γ'-fibrinogen concentration (P < .05). CONCLUSION: Our data reveal: (1) elevated γ' fibrinogen concentrations in obese insulin-resistant children compared with normal lean controls; (2) a relationship between γ' fibrinogen and other CVD risk factors; and (3) physical activity-induced reduction in γ' fibrinogen in obese children.

Biomarkers for cardiovascular risk in children.

PURPOSE OF REVIEW: The magnitude of lifetime risk of cardiovascular disease (CVD) has radically increased along with the high prevalence of obesity in children. The spotlight is now on dysfunctional adiposity as a precursor for the development of premature CVD. As full-blown CVD is not present in childhood, there is a critical need for surrogate markers to best assess, predict, and treat the children who are vulnerable to developing CVD. RECENT FINDINGS: Accumulation of excess fat mass can be conceived as a derangement in the balance between energy intake and expenditure. This appears to provoke various structural and metabolic alterations leading to adipocyte dysfunction, with important cardiovascular health consequences. Subclinical inflammation, insulin resistance, oxidative stress, and endothelial dysfunction appear to play important roles early in the clinical course of obesity. SUMMARY: Associations between biomarkers and noninvasive measures of early atherosclerosis in children continue to emerge and several biomarkers appear to be promising. At present, there are no explicit data to recommend any of these biomarkers as a routine clinical marker of CVD in children. More work is needed to validate these biomarkers and to improve understanding of their role in CVD risk prediction in the pediatric population.

Effects of surgically induced weight loss by Roux-en-Y gastric bypass on osteocalcin.

BACKGROUND: Osteocalcin (OC), a protein synthesized by osteoblasts, is a marker of bone turnover with undercarboxylated OC (ucOC) being involved in glucose homeostasis. Although laparoscopic Roux-en-Y gastric bypass (LRYGB)-induced weight loss likely alters bone turnover, data on markers of bone turnover remain less clear. The aim of this study was to examine the effect of surgically induced weight loss on OC and ucOC. METHODS: A total of 32 individuals with a body mass index 50.2±10.2 kg/m(2) underwent LRYGB. Osteocalcin, ucOC, other blood analytes (e.g., vitamin D, leptin, total and high-molecular-weight adiponectin), and homeostasis model assessment for insulin resistance were measured before and after weight loss. The effect of an acute nutrient load on OC parameters after a mixed meal tolerance test also was assessed. RESULTS: Six months after surgery, there was an increase in OC (17.8±7.4 [mean±SD] [baseline] versus 31.5±9.8 ng/mL [follow-up]; P<.001) and ucOC (7.3±6.2 versus 18.5±8.9 ng/mL; P<.001). Although adiponectin increased, only the magnitude of change in OC and leptin was correlated (r =-.43; P = .017). After weight loss, an acute nutrient load reduced OC (31.5±9.8 [0-hour] versus 29.6±8.2 [2-hour] ng/mL; P = .024), whereas ucOC was higher (18.8±9.3 [0-hour] versus 21.1±8.6 [2-hour] ng/mL; P< .001). CONCLUSION: Surgically induced weight loss was associated with increases in OC and ucOC. Underlying mechanisms are unclear, but change in OC may be related to change in leptin. After a nutrient load, the increase in ucOC suggests a potential role as a short-term compensatory regulator of glucose homeostasis.

Metformin use in children with obesity and normal glucose tolerance--effects on cardiovascular markers and intrahepatic fat.

OBJECTIVE: To determine if metformin improves markers of inflammation, thrombosis, and intrahepatic fat contents in children with uncomplicated obesity. METHODS: Obese children with normal glucose tolerance but elevated highly sensitive C-reactive protein (hsCRP) and/or fibrinogen concentrations (>2 standard deviations) were randomized to structured diet/exercise or diet/exercise and metformin for 6 months. Blood samples, dual energy X-ray absorptiometry data, and liver magnetic resonance images were obtained. RESULTS: Forty-two of 66 recruited children (7-18 years) completed 6 months. Weight loss was modest but more pronounced in the metformin group (-4.9 +/- 1.0 kg) than in the diet/exercise group (-1.7 +/- 1.1 kg, p<0.03), whereas hsCRP and fibrinogen decreased more in the diet/exercise pubertal group. Baseline intrahepatic fat was high but decreased only in the diet/exercise (not metformin) pubertal group. CONCLUSIONS: Six months of metformin therapy improved weight loss and reduced abdominal adiposity, but did not enhance the beneficial effect of diet and exercise on markers related to inflammation, thrombosis, or hepatic fat in obese children with normal glucose tolerance.

Insulin resistance and adiposity in relation to serum ß-carotene levels.

OBJECTIVE: To determine the effects of placebo vs an encapsulated supplement of fruit and vegetable juice concentrate (FVJC) on serum ß-carotene levels, insulin resistance, adiposity, and subclinical inflammation in boys. STUDY DESIGN: Thirty age-matched prepubertal boys (9 lean and 21 overweight (OW); age range, 6-10 years) were studied. All participants received nutrition counseling and were randomized to receive FVJC or placebo capsules for 6 months. Total cholesterol, triglycerides, lipid corrected ß-carotene, serum retinol, glucose, insulin, retinol binding protein-4, leptin, adiponectin, leptin-to-adiponectin ratio, high-sensitivity C-reactive protein, and interleukin-6 were measured before and after the 6-month intervention. Homeostasis model assessment-insulin resistance (HOMA-IR), acute insulin response to intravenous glucose, along with abdominal fat mass (dual-energy x-ray absorptiometry) were also determined. RESULTS: Baseline ß-carotene concentrations correlated inversely with HOMA-IR, leptin-to-adiponectin ratio, and abdominal fat mass (P ≤ .01). FVJC intake increased ß-carotene concentrations (P ≤ .001) but did not influence retinol or retinol binding protein-4. Retinol insufficiency <1.047 µM was present in 18% of the entire cohort at baseline and in 37% at 6 months. HOMA-IR decreased after supplementation in the OW cohort, when adjusted for percent weight change (P = .014). The percent change in abdominal fat mass increased in the placebo group and decreased in the FVJC group (P = .029). CONCLUSIONS: A 6-month supplementation with FVJC in the presence of nutritional counseling was associated with an increase in serum ß-carotene concentrations and a reduction in adiposity in conjunction with an improvement in insulin resistance in OW boys.

Lifestyle intervention improves fitness independent of metformin in obese adolescents.

PURPOSE: Obesity in adolescence increases the risk for early adult cardiovascular disease. We recently showed that 6 months of diet, exercise, and metformin resulted in reductions in adiposity and that diet/exercise alone reduced proinflammatory factors and intrahepatic fat in pubertal children with uncomplicated obesity. The purpose of the present study was to determine whether changes in cardiorespiratory fitness (CRF) after 6 months of structured diet and exercise (DE) or DE plus metformin are related to the previously observed changes in adiposity, markers of inflammation, and intrahepatic fat. METHODS: Sixteen obese pubertal adolescents between the ages of 10 and 17 were randomized into a structured lifestyle program consisting of DE or DE plus metformin. Subjects performed aerobic and resistance exercise 3 d·wk⁻¹, 30 min per session. Cycle ergometer maximal oxygen consumption (V˙O2max), body composition, blood markers (glucose, insulin, homeostatic model assessment-insulin resistance, interleukin-6, hsCRP), and intrahepatic fat were measured at baseline and 6 months. RESULTS: In the cohort, as whole-body weight decreased by 4.0% (P = 0.009), body mass index decreased by 4.9% (P = 0.003), percent body fat decreased by 8.8% (P < 0.001), and V˙O2max improved in 10 of 16 subjects. The addition of metformin provided no further effect on body composition, CRF, or inflammatory factors. More favorable changes in adiposity, adiponectin, and a trend toward blood glucose and interleukin-6 concentrations (P = 0.07) were observed in subjects who increased V˙O2max at 6 months (n = 10) compared with no change in these variables in those who did not improve V˙O2max. CONCLUSIONS: Metformin did not provide benefits above lifestyle modification for improving CRF in obese adolescents. Improvements in V˙O2max seem to be associated with more favorable metabolic outcomes.

Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association.

The rapid increase in the prevalence and severity of obesity in children is likely to lower the age of onset and increase the incidence of cardiovascular disease worldwide. Understanding the pathophysiology and improving the clinical management of cardiovascular disease involve a knowledge of novel risk factors and biomarkers. The clinical and mechanistic roles of these novel biological factors during childhood are currently being investigated. The goals of this scientific statement are to present the existing knowledge and theoretical framework of nontraditional risk factors for cardiovascular disease as they relate to children and adolescents, to describe the relevance and weight of available experimental and clinical evidence and the therapeutic implications pertaining to nontraditional risk factors in the pediatric population, and to stimulate further research with a goal of developing valid and reliable approaches to identify and validate novel risk factors that will aid in the clinical evaluation and perhaps prediction of cardiovascular disease in the pediatric population. Although several biomarkers are promising, substantial research is required before nontraditional risk factors can be used to identify and reduce cardiovascular disease risk in children and adolescents.

Effects of growth hormone and nutritional therapy in boys with constitutional growth delay: a randomized controlled trial.

OBJECTIVE: To examine whether supplemental nutrition augments the anabolic actions of growth hormone (GH) in boys with constitutional delay of growth and maturation (CDGM). STUDY DESIGN: We conducted a randomized, controlled trial at an outpatient clinical research center. Subjects were 20 prepubertal boys (age, 9.3 ± 1.3 years) with CDGM (height standard deviation score, -2.0 ± 0.5; bone age delay, 1.8 ± 0.8 years; body mass index standard deviation score, -1.2 ± 1.0; peak stimulated GH, 15.7 ± 7.7 ng/mL), who were randomized (n = 10/group) to 6 months observation or daily nutritional supplementation, followed by additional daily GH therapy in all for another 12 months. t tests and repeated measures analyses of variance compared energy intake, total energy expenditure (TEE), growth, hormones, and nutrition markers. RESULTS: Energy intake was increased at 6 months within the nutrition group (P = .04), but not the observation group, and TEE was not statistically different within either group at 6 months. Addition of 6 months GH resulted in higher energy intake and TEE in the GH/nutrition group at 12 months (P < .01), but not in the GH group versus baseline. Height, weight, lean body mass, hormones, and nutrition markers increased comparably in both groups throughout 18 months. CONCLUSION: Boys with CDGM use energy at an accelerated rate, an imbalance not overcome with added nutrition. GH therapy increases growth comparably with or without added nutrition in these patients.

Changes in circulating satiety hormones in obese children: a randomized controlled physical activity-based intervention study.

The aims of this study are to examine in children: (i) obesity-related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity-based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 +/- 0.6 for 15 obese and 56.2 +/- 1.1 for 6 lean). The obese subjects underwent a 3-month randomized controlled physical activity-based lifestyle intervention. Leptin, soluble leptin receptor (sOB-R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual-energy X-ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB-R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB-R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity-based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk.

Obesity without established comorbidities of the metabolic syndrome is associated with a proinflammatory and prothrombotic state, even before the onset of puberty in children.

BACKGROUND: Metabolic syndrome (MS)-related comorbidities in obesity, such as hypertension, dyslipidemia, and glucose intolerance, are increasingly recognized in children, predisposing them to early cardiovascular disease. OBJECTIVE: The objective of the study was to investigate whether markers of inflammation and prothrombosis are abnormal in obese children without established MS comorbidities across puberty, as compared with lean, age-matched controls. SUBJECTS AND METHODS: Obese children (body mass index >95%) with normal fasting glucose, blood pressure, cholesterol and triglycerides were recruited; lean controls (body mass index 10-75%) had no first-degree relatives with MS. High-sensitivity C-reactive protein (hsCRP), IL-6, plasminogen activator inhibitor 1, and fibrinogen concentrations were measured. Body composition was assessed by waist circumference and dual-energy x-ray absorptiometry. RESULTS: Of 623 children screened, 203 enrolled (106 males, 97 females), aged 7-18 yr, 115 obese, 88 lean (balanced for age and gender), 99 prepubertal, and 104 pubertal. Many screen failures were due to silent comorbidities. Obese subjects with insulin resistance but without MS comorbidities had about 10 times higher hsCRP concentrations than controls and higher fibrinogen, IL-6, and plasminogen activator inhibitor-1 (P < 0.01 all). Differences were significant, even in the prepubertal cohort. hsCRP and fibrinogen correlated with waist circumference (r = 0.73 and 0.40, respectively) and percent fat mass (r = 0.76 and 0.47) (P < 0.0001). CONCLUSION: Childhood obesity per se is associated with a proinflammatory and prothrombotic state before other comorbidities of the MS are present and even before the onset of puberty. Whether biomarkers like hsCRP and fibrinogen are useful in assessing cardiovascular risk and whether these abnormalities are reversible with earlier therapeutic interventions in very young obese children requires further study.

Metabolic effects of oral versus transdermal estrogen in growth hormone-treated girls with turner syndrome.

BACKGROUND: Transdermal (TD) estrogen is often preferred over the oral route in postmenopausal and GH-deficient women taking estrogen, but this has not been studied in detail in girls. OBJECTIVE: Our objective was to study the metabolic effects of oral vs. TD estrogen in GH-treated girls with Turner syndrome. DESIGN AND METHODS: Eleven girls with Turner syndrome, mean age 13.4 +/- 0.5 (se) yr, on GH for at least 6 months were recruited. Studies included [(13)C]leucine and d5-glycerol infusions, indirect calorimetry, dual-emission x-ray absorptiometry, and hormone and substrate measurements. They received, in random order, 17beta-estradiol orally (0.5, 1, and 2 mg for 2 wk each) and TD (0.025, 0.0375, and 0.05 mg for 2 wk each), and studies were repeated after each 6-wk course with 4 wk washout in between. RESULTS: Rates of whole-body protein turnover, oxidation and synthesis, lipolysis, lipid and carbohydrate oxidation, and resting energy expenditure were unaffected by either form of estrogen; nor were lipids, insulin, and fibrinogen concentrations affected. Plasma IGF-I concentrations did not change clinically significantly with either form of estrogen, despite higher estrogen concentrations after oral estrogen. Estradiol concentrations did not correlate with any variables measured. CONCLUSIONS: In GH-treated girls with Turner syndrome, neither oral nor TD estrogen adversely affected rates of protein turnover, lipolysis, and lipid oxidation rates or plasma lipids, fibrinogen, or fasting insulin concentrations. There was no clinically significant change in IGF-I concentrations after either form of estrogen. In aggregate, these data suggest that the route of delivery of estrogen does not adversely affect these metabolic effects of GH in young girls with Turner syndrome.

Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation.

CONTEXT: Retinol binding protein (RBP4), secreted primarily from the liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity, its relationship with subclinical inflammation, and its response to lifestyle changes are not elucidated. OBJECTIVE: The objective of the study was to determine in children: 1) the status of RBP4 levels in lean vs. obese; 2) the relationship between RBP4 levels and subclinical inflammation; and 3) the effect of lifestyle-only intervention on RBP4 levels. DESIGN, SETTING, AND PATIENTS: Lean and obese children (n = 21) matched for age (>14 yr to < 18 yr) and maturity stage (Tanner IV) were studied at baseline and with lifestyle intervention in obese subjects only (n = 15). INTERVENTION: Patients received 3 months of randomized and controlled physical activity-based lifestyle intervention. MAIN OUTCOME MEASURE: RBP4 levels in children before and after intervention and the relationship between RBP4 and subclinical inflammation were measured. RESULTS: Higher RBP4 levels were found in the obese group vs. lean group (P = 0.005). RBP4 correlated with not only indices of obesity and insulin resistance but also inflammatory factors (r = 0.63 and 0.64 for C-reactive protein and IL-6, respectively, P < 0.01). Intervention reduced RBP4 levels by approximately 30% (P = 0.001), and RBP4 reduction was correlated with the magnitude of decrease in inflammatory factors (P = 0.01). CONCLUSION: Alterations in serum RBP4 occur at an early age in the clinical course of obesity and appear to correlate with subclinical inflammation. Lifestyle intervention almost entirely reversed the raised RBP4 levels in obese children. Future studies should determine whether elevation of RBP4 is a direct trigger for the insulin resistance and subclinical inflammation implicated in the premature development of cardiovascular disease and diabetes.

Physical activity and cardiovascular health in children.

The rapid growth in the prevalence of obesity in children and the tracking of obesity from childhood to adulthood can predispose children to type 2 diabetes and CVD at an early age. Strategies to prevent obesity and its complications are of urgent importance. In view of the enormous cardio-protective role of physical activity, pediatricians should implement more intensely preventive strategies based on physical activity, diet, and behavior. This approach is crucial as an effective form of prevention of development of diabetes and CVD, as well as a therapy for children with risk factors for CVD. However, this is a complex task and requires a unified approach that involves environmental, behavioral, cultural, economic, legislative, and physiological factors, as well as a favorable environment that promotes physical activity along with healthy dietary habits.

Oxandrolone enhances skeletal muscle myosin synthesis and alters global gene expression profile in Duchenne muscular dystrophy.

Earlier studies have shown that the progressive, unrelenting muscle loss associated with Duchenne muscular dystrophy (DMD) involves an imbalance between the rates of synthesis and degradation of muscle proteins. Although previous studies have suggested that oxandrolone may be beneficial in DMD, the mechanism of action of oxandrolone on muscle in DMD remains unclear. To address these issues, we combined stable isotope studies and gene expression analysis to measure the fractional synthesis rate of myosin heavy chain (MHC), the key muscle contractile protein, the transcript levels of the isoforms of MHC, and global gene expression profiles in four children with DMD before and after 3 mo of treatment with oxandrolone. Gastrocnemius muscle biopsies and blood samples were collected during the course of a primed 6-h continuous infusion of l-[U-(13)C]leucine on two separate occasions, before and after the 3-mo treatment with oxandrolone (0.1 mg.kg(-1).day(-1)). Gene expression analysis was done with microarrays and RT-qPCR. In response to the treatment, MHC synthesis rate increased 42%, and this rise was accounted for, at least in part, by an upregulation of the transcript for MHC8 (perinatal MHC). Gene expression data suggested a decrease in muscle regeneration as a consequence of oxandrolone therapy, presumably because of a decrease in muscle degeneration. These findings suggest that 1) oxandrolone has a powerful protein anabolic effect on a key contractile protein and 2) larger and longer-term studies are warranted to determine whether these changes translate into meaningful therapy for these patients.

Obesity-related cardiovascular risk in children and the role of lifestyle changes.

Overweight and obesity in children present significant public health concerns because of the link with numerous chronic health conditions, especially type 2 diabetes and cardiovascular disease. Perhaps obesity is only the visible pointer of other underlying risk factors for these disease conditions in childhood. Although an imbalance between energy consumed and expended appears to be the simplistic underlying problem for the increased prevalence of obesity, it is a complex condition, with various contributing factors, and may be considered the metabolic factory for various risk factors for cardiovascular disease, both modifiable and nonmodifiable. It has also been recognized that the risk factors emerge quite early in the clinical course of obesity. Physical activity-based lifestyle change appears to be the most variable component of energy expenditure and therefore has been the obvious choice and the target of behavioral interventions to modify body weight in children. This review focuses on the obesity-related nontraditional risk factors for cardiovascular disease in children and the role of lifestyle changes in modulating these risk factors.

Reversal of obesity-related hypoadiponectinemia by lifestyle intervention: a controlled, randomized study in obese adolescents.

CONTEXT: Hypoadiponectinemia and chronic subclinical inflammation in adults are associated with the development of diabetes and cardiovascular disease. The potential relationship between adiponectin and inflammation and its modulation by lifestyle intervention in the pediatric obese population remain unclear. OBJECTIVES: The objectives were to investigate in adolescents 1) the relationship between adiponectin and obesity-related inflammatory factors, C-reactive protein, and IL-6; and 2) the effect of a lifestyle intervention on adiponectin and whether these effects are related to changes in inflammatory factors. RESEARCH METHODS AND PROCEDURES: Twenty-one obese and age-matched lean adolescents (age, 14-18 yr; Tanner stage, > or =IV) were studied cross-sectionally. Fifteen obese adolescents also underwent a randomized, controlled physical activity-behavior-diet-based lifestyle intervention for 3 months. Associations among adiponectin, fat mass, insulin resistance, and inflammatory factors at baseline as well as after the intervention were assessed. RESULTS: Plasma adiponectin concentration was lower (P < 0.001) in the obese vs. age-matched lean adolescents. Significant inverse relationships were observed between adiponectin and inflammatory factors, insulinemia, insulin resistance, and fat mass. Intervention produced a 34% increase in adiponectin concentration (P = 0.0004) despite negligible weight loss but with reductions in fat mass, hyperinsulinemia, insulin resistance, and inflammatory factors (all P < 0.01). CONCLUSIONS: The data suggest that in adolescents, obesity-related hypoadiponectinemia is associated with subclinical inflammation, and a short-term lifestyle intervention augments adiponectin concentrations. These effects appear to be related to reductions in fat mass and inflammatory factors. Based on our current understanding of adiponectin physiology, reversal of hypoadiponectinemia in obese adolescents may protect against risks for cardiovascular disease and diabetes.

Lifestyle-only intervention attenuates the inflammatory state associated with obesity: a randomized controlled study in adolescents.

OBJECTIVES: The primary goals were to understand the relationship among the inflammatory factors, C-reactive protein (CRP), interleukin-6 (IL-6), and fibrinogen, and indices of obesity in normoglycemic, insulin-resistant adolescents and to investigate the impact of a lifestyle-only intervention on these nontraditional risk factors for cardiovascular disease (CVD). STUDY DESIGN: Randomized controlled lifestyle-only intervention study in adolescents. Of the 21 adolescents studied, 15 obese subjects (body mass index [BMI] = 37.6 +/- 3.3 kg/m 2 ) were randomized to either a lifestyle intervention program or usual care. The lean controls were studied only at baseline. Analysis of variance (ANOVA) for repeated measures was used to study intervention effect and t test, one-way ANOVA, and discriminant function analysis for baseline comparisons. RESULTS: The intervention group maintained weight, whereas the control group gained weight (P = .02). A redistribution of body composition and a decrease in insulin resistance were observed. Elevated circulating concentrations of CRP, fibrinogen, and IL-6 were significantly reduced (all P