Differences in Weight and Fitness Status in Both the GH-IGF1 Axis and Markers of Inflammation in Adolescents

PURPOSE: To determine if differences in the GH-IGF1 axis and TNF-α or IL-6 exist in children based on fitness and/or weight status and if expressing fitness in units per fat free mass (FFM) alters the relationship between the GH-IGF1 axis components, TNF-α, and IL-6. Additionally, the influence that inflammatory markers have on the relationship between components of the GH-IGF1 axis was assessed. PARTICIPANTS: Data was collected on 124 youth purposefully selected from a larger study (CHIC III, J.S. Harrell, P.I.) into four groups: normal high fit (NH), normal low fit (NL), obese high fit (OH), and obese low fit (OL). METHODS: Height, weight, skinfolds, body mass index (BMI), body fat percentage and predicted VO2max (mL/min) were measured. Predicted VO2max was scaled to VO2max (mL/kgFFM/min) and used to determine fitness status. Resting growth hormone (GH), total insulin-like growth factor-1 (total IGF1), free insulin-like growth factor-1(free IGF1), insulin, TNF-α, and IL-6 were obtained from fasting blood samples. RESULTS: GH was significantly greater in the NH group compared to the OL group. Total IGF1, free IGF1, and TNF-α were not different in any of the groups. Insulin was greater in the OH and OL groups compared to the NH and NL groups. IL-6 was elevated in the NL and OL groups compared to the NH group and in the OL group compared to the OH group. Significant correlations between GH-IGF1 axis components existed between GH and total IGF1 (r=0.194, p=0.05) and free IGF1 and total IGF1 (r=0.607, p<0.001) only. Neither TNF-α nor IL-6 contributed to the relationship between GH and total IGF1. Only IL-6 had a significant relationship (β=-0.060, p=0.030) between free IGF1 and total IGF1 when fitness was included in the model. CONCLUSIONS: Fitness may reduce the obesity related GH alterations possibly involved with continued weight gain. IL-6 levels appear more affected by fitness then fat mass. When including fitness, IL-6 may influence the GH-IGF1 axis. The relationship between GH-IGF1 axis, TNF-α, or IL-6 does not change when using VO2max scaled to total body mass versus FFM. Findings suggest that elevated aerobic fitness may limit continued weight gain

Changes in Plasma Potassium During Graded Aerobic Exercise and Two Hours of Recovery

Plasma potassium increases with exercise intensity. Subjects (n=8) were monitored for changes in plasma potas-sium while exercising at progressively increasing steady-state intensities and for two hours of recovery. Plasma po-tassium was significantly increased at 100% of VO2peak compared to 20% and 40% (p<0.01). Plasma potassium at 60 and 120 minutes of recovery from exercise was significantly higher than 6 minutes post exercise (p<0.015). These results support the supposition that high-intensity exercise may lead to hyperkalemia, and also indicates that in-creases in [K + ] occur up to two hours after the cessation of exercise, a newly reported phenomenon. Although, high levels of plasma potassium are known to cause cardiac abnormalities and related events, exercise induced changes in normal healthy adults are not currently believed to have clinical implications

Original Research Oral Quercetin Supplementation and Blood Oxidative Capacity in Response to Ultramarathon Competition

Previous research indicates that ultramarathon exercise can result in blood oxidative stress. The purpose of this investigation was to examine the efficacy of oral supplementation with quercetin, a naturally occurring compound with known antioxidant properties, as a potential countermeasure against blood oxidative stress during an ultramarathon competition. In double-blind fashion, 63 participants received either oral quercetin (250 mg, 4×/day; 1,000 mg/day total) or quercetin-free supplements 3 weeks before and during the 160-km Western States Endurance Run. Blood drawn before and immediately after (quercetin finishers n = 18, quercetin-free finishers n = 21) the event was analyzed for changes in blood redox status and oxidative damage. Results show that quercetin supplementation did not affect race performance. In response to the ultramarathon challenge, aqueous-phase antioxidant capacity (ferric-reducing ability of plasma) was similarly elevated in athletes in both quercetin and quercetin-free treatments and likely reflects significant increases in plasma urate levels. Alternatively, trolox-equivalent antioxidant capacity was not altered by exercise or quercetin. Accordingly, neither F2-isoprostances nor protein carbonyls were influenced by either exercise or quercetin supplementation. In the absence of postrace blood oxidative damage, these findings suggest that oral quercetin supplementation does not alter blood plasma lipid or aqueous-phase antioxidant capacity or oxidative damage during an ultramarathon challenge

LPS INHIBITION OF GLUCOSE PRODUCTION THROUGH THE TLR4, MYD88, NFκB PATHWAY

Acute exposure to lipopolysaccharide (LPS) can cause hypoglycemia and insulin resistance; the underlying mechanisms however, are unclear. We set out to determine whether insulin resistance is linked to hypoglycemia through TLR4, MyD88 and NFκB, a cell signaling pathway that mediates LPS induction of the proinflammatory cytokine TNFα. LPS induction of hypoglycemia was blocked in TLR4−/− and MyD88−/− mice but not in TNFα−/− mice. Both glucose production and glucose utilization were decreased during hypoglycemia. Hypoglycemia was associated with the activation of NFκB in the liver. LPS inhibition of glucose production was blocked in hepatocytes isolated from TLR4−/− and MyD88−/− mice and hepatoma cells expressing an IκB mutant that interferes with NFκB activation. Thus, LPS-induced hypoglycemia was mediated by the inhibition of glucose production from the liver through the TLR4, MyD88, NFκB pathway, independent of LPS induced TNFα. LPS inhibition of glucose production was not blocked by pharmacologic inhibition of the insulin signaling intermediate PI3K in hepatoma cells. Insulin injection caused a similar reduction of circulating glucose in TLR4−/− and TLR4+/+ mice. These two results suggest that LPS and insulin inhibit glucose production by separate pathways. Recovery from LPS induced hypoglycemia was linked to glucose intolerance and hyperinsulinemia in TLR4+/+ mice, but not in TLR4−/− mice

Heme Oxygenase, a Novel Target for the Treatment of Hypertension and Obesity?

Heme oxygenase (HO) is the rate-limiting enzyme in the metabolism of heme-releasing bioactive molecules carbon monoxide (CO), biliverdin, and iron, each with beneficial cardiovascular actions. Biliverdin is rapidly reduced to bilirubin, a potent antioxidant, by the enzyme biliverdin reductase, and iron is rapidly sequestered by ferritin in the cell. Several studies have demonstrated that HO-1 induction can attenuate the development of hypertension as well as lower blood pressure in established hypertension in both genetic and experimental models. HO-1 induction can also reduce target organ injury and can be beneficial in cardiovascular diseases, such as heart attack and stroke. Recent studies have also identified a beneficial role for HO-1 in the regulation of body weight and metabolism in diabetes and obesity. Chronic HO-1 induction lowers body weight and corrects hyperglycemia and hyperinsulinemia. Chronic HO-1 induction also modifies the phenotype of adipocytes in obesity from one of large, cytokine producing to smaller, adiponectin producing. Finally, chronic induction of HO-1 increases oxygen consumption, CO 2 , and heat production and activity in obese mice. This review will discuss the current understanding of the actions of the HO system to lower blood pressure and body weight and how HO or its metabolites may be ideal candidates for the development of drugs that can both reduce blood pressure and lower body weight

The Interaction of Obesity and Puberty On Substrate Utilization During Exercise: A Gender Comparison

The study evaluated the interactions of puberty and obesity on substrate oxidation of overweight girls (n = 38) and boys (N = 35; BMI \u3e 85th percentile) matched for gender, age, and puberty (pre/pubertal) with normal weight girls and boys. Metabolic rates (VO2) were obtained during rest and at 4, 5.6 and 8 k/h. Carbohydrate oxidation rates (mg/kgFFM/min) adjusted for % predicted VO2max, were higher for prepubertal OW children than pubertal children (p \u3c.03). Fat oxidation rates were higher for NW prepubertal boys compared with other boys. Results indicate that OW children, regardless of gender or pubertal status, increase their carbohydrate oxidation rate to compensate for higher than normal metabolic rates. The effects of obesity on the substrate use is marginally related to puberty

Cardiorespiratory Fitness and the Relationship Between Body Fat and Resting Testosterone in Men

Objective: To examine the effect of cardiovascular fitness, i.e. VO2max, on the relationship between weight status and resting testosterone level (RTL) in males. Materials and methods: A subset of male participants from the 2003–2004 National Health and Nutrition Examination Survey were analyzed by weight status, i.e. normal, overweight, obese, and all participants. Bivariate correlation coefficients were computed for RTL, percent body fat (BF%), and VO2max. Partial correlation coefficients were computed between RTL and BF% controlling for VO2max and between RTL and VO2max controlling for BF%. Results: Bivariate correlations between RTL and BF%, and RTL and VO2max were significant in all groups. The partial correlation coefficients between RTL and BF% controlling for VO2max were significant in the normal and all participants group. When RTL and VO2max were analyzed controlling for BF% only the all participants group remained significant. Conclusion: Cardiovascular fitness or weight status may independently influence RTL in males

Bioelectrical impedance analysis does not detect an increase in total body water following isotonic fluid consumption

Purpose: To determine if single-frequency foot-to-foot bioelectrical impedance analysis (BIA) can detect acute changes in total body water (TBW) following consumption of isotonic saline. All participants ate a sodium-free meal at 4 h prior to the data collection visit and had euhydration confirmed using urine specific gravity at the beginning of the experimental visit. Subjects drank 466 mL of isotonic saline (Na+ 140 mmol·L−1) following baseline measures. Blood sampling and BIA were performed at baseline and every 30 min for 3 h after saline consumption. Ten healthy participants completed this study. Plasma volume (5%Δ, p < 0.001) and serum sodium concentration (1%Δ, p < 0.001) increased by 60 min and 90 min, respectively. Body mass (p < 0.001) displayed a biphasic response increasing to a peak at 30 min (+0.38Δkg) and then decreasing to its minimum at 180 min (–0.35Δkg). BIA impedance (p = 0.678) was unaffected by the saline administration. BIA-derived TBW (p = 0.039) decreased from baseline starting at 150 min (0.21Δkg). Novelty Athletes and coaches wishing to achieve hyperhydration can do so through the consumption of isotonic fluid. 50 kHz foot-to-foot BIA-derived TBW is inadequate for measuring hyperhydration. Future studies should examine the physiological and performance effects of such a hyperhydration protocol.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Importance of Proper Scaling of Aerobic Power When Relating to Cardiometabolic Risk Factors In Children

Background: The relationship between cardiometabolic risk factors (CMRF) and aerobic power (VO 2max) scaled as mL O2 per kilogram body mass is controversial because mass includes both fat and fat-free mass, and fat mass is independently associated with the CMRF. Aim: To examine common units used to scale VO 2max and their relationships to mean blood pressure (MBP), total cholesterol (TC), HDL cholesterol, triglycerides (TG), insulin resistance (HOMA-IR) and cumulative risk score (z-score). Subjects: 1784, 8-18 year-old youths, 938 girls and 886 boys. Methods: Fasting blood samples were obtained. VO 2max was estimated in mL/min from cycle ergometry and scaled to body mass (kg), fat free mass (kgFFM), body surface area (m 2), height (cm) and allometric (mL/kg 0.67/min). Results: Unadjusted correlations between CMRF and many of the scaled VO 2max units were significant (p \u3c 0.0001), especially for MBP, HOMA-IR, HDL and z-score, with lower correlations for TC and TG. After adjusting for ancestry, sex, height and body fat associations were greatly weakened (r \u3c 0.09), except for MBP. Conclusions: On a population basis, the physical characteristics of the child, especially body fat, are more related to CMRF than any scaled units of VO 2max; thus care is needed when relating fitness and health issues