Metabolism: clinical and experimental
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Comparative Study
Associations of middle-aged mother's but not father's body mass index with 18-year-old son's waist circumferences, birth weight, and serum hepatic enzyme levels.
Mitochondrial dysfunction has been reported to contribute to insulin resistance (IR) in the elderly and type 2 diabetes. To test this hypothesis, we examined relations of insulin resistance in young men to their mother's body mass index (BMI) and compared with those to their father's BMI, because as a rule, mitochondrial DNA is exclusively maternally inherited and because mitochondria are fundamental in mediating effects on energy dissipation. We measured heights, weights, waist circumference, systolic and diastolic blood pressure (BP), and biochemical variables in sera from 193 male college students aged 18 to 20 years after an overnight fast. ⋯ After adjustment for sons' BMI, waist circumference and 3 hepatic enzymes were associated with mother's BMI, whereas Lp(a) was associated with both mother's and father's BMI. In multiple regression analysis for HOMA-IR as a dependent variable, BMI of their own (beta=.10, P<.0001) and of their mothers (beta=.04, P=10) and birth weight (beta=-.27, P=.10) emerged as determinants of HOMA-IR of the students(R2=0.30). Our results are consistent with clinical observations of a greater risk of transmission of type 2 diabetes from the mother than the father and suggest that son's IR may be influenced by maternal effect as well as their adiposity.
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Randomized Controlled Trial Clinical Trial
Relationship between S-adenosylmethionine, S-adenosylhomocysteine, asymmetric dimethylarginine, and endothelial function in healthy human subjects during experimental hyper- and hypohomocysteinemia.
Experimental hyperhomocysteinemia after an oral methionine or homocysteine load is associated with impaired nitric oxide-dependent vasodilatation in healthy human beings. However, it remains unproven that this effect is mediated by elevations in plasma homocysteine. There is evidence that an increase in plasma homocysteine may increase the formation of asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase. ⋯ Plasma S-adenosylmethionine/S-adenosylhomocysteine ratio was significantly (P < .001) increased at 4 hours after methionine (10.9 +/- 0.7) compared with homocysteine (5.4 +/- 0.4), NAC (5.0 +/- 0.3), and placebo (6.0 +/- 0.5). Plasma ADMA concentrations were not altered by any intervention. Our results suggest that endothelial dysfunction due to methionine or homocysteine loading is not associated with an increase in plasma ADMA or a disruption in methylation status.
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Clinical Trial
Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity.
The aims of the present study was to examine how overweight and obesity affect serum concentrations nitric oxide (NO) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors (sTNF-R) in subjects with overweight and obesity. The study groups involved 154 women: 102 obese (81 obese with body mass index [BMI] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2), 24 overweight patients, and 28 lean controls. Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors (sTNF-R1, sTNFR-2) were measured by enzyme-linked immunosorbent assay (ELISA) kits. ⋯ However, serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group, both obese groups, and controls. In conclusion, we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women. It seems that there is an association between serum concentrations of TNF-alpha and NO; however, this relationship depends on the degree of obesity.
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Uncoupling protein-1 (UCP-1) plays a major role in thermogenesis, and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of A-3826G polymorphism of the UCP-1 gene on the plasma lipid profiles in 190 Korean obese subjects with a body mass index (BMI) more than 30 kg/m2. Height, weight, BMI, wait-to-hip ratio (WHR), obesity index, and body composition were measured and genotype of UCP-1 was analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. ⋯ When the subjects were divided into a normal group and a hyper-LDL cholesterolemia group by LDL cholesterol level of 3.626 mmol/L (140 mg/dL), the frequency of hyper-LDL cholesterolemia was significantly higher in GG type compared with other types by Fisher's exact (chi-square) test (P = .05). When logistic regression analysis was conducted to find the risk factors of hyper-LDL cholesterolemia, the odds ratio was 4.115 (P = .03) for GG type of UCP-1 gene. These results suggest that the GG type of the UCP-1 gene has a strong association with increased LDL cholesterol level and might be a significant risk factor for hyper-LDL cholesterolemia among Korean obese subjects.
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Comparative Study Clinical Trial
Are peristaltic pumps as reliable as syringe pumps for metabolic research? Assessment of accuracy, precision, and metabolic kinetics.
Syringe pumps are traditionally used to infuse tracers in metabolic research because they are perceived to be more accurate and precise than peristaltic pumps. This study evaluated the accuracy (actual v programmed infusion rate) and precision (reproducibility of infusion) of a peristaltic pump (Gemini PC 2; IMED, San Diego, CA) and a syringe pump (Model 22; Harvard Apparatus, Natick, MA) for metabolic research. In one protocol, saline delivery was measured in vitro in 5 trials at 4 flow rates: 3, 30, 150, and 300 mL/h. ⋯ Glycerol Ra values were the same when tracer was infused with either a syringe or peristaltic pump on day 1 and day 2: 4.1 +/- 1.7 (syringe pump) and 4.2 +/- 1.9 (peristaltic pump) micromol. kg fat mass (FM)(-1). min(-1) on day 1; 4.2 +/- 1.2 (syringe pump) and 4.2 +/- 1.3 (peristaltic pump) micromol. kg FM(-1). min(-1) on day 2. These data demonstrate that both syringe and peristaltic pumps are very accurate and precise across a large range of flow rates. Moreover, the assessment of in vivo substrate kinetics in human subjects is the same when either pump is used to infuse isotope tracers.