Background-Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance.In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women. (rϭ0.58, PϽ0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of MV O 2 and efficiency (Pϭ0.0005 and PϽ0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (PϽ0.05, Ͻ0.005, and Ͻ0.005, respectively). Conclusions-In young women, obesity is a significant predictor of increased MV O 2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.

No abstract

The doubly labeled water method for measuring energy expenditure can be very sensitive to small differences in the ratio of the 2H to 18O isotope dilution spaces. Recently it has been suggested that the average ratio is higher than the 1.03 we previously recommended. We therefore combined the data from 99 recently studied subjects. Subjects (85 females and 14 males) were between the ages of 4 and 78 yr (mean = 34 yr) and between 10 and 52% (mean = 35%) fat. The average 2H-to-18O dilution space ratio was 1.034 +/- 0.014, which was very similar to the original assumption. As in recent reports, we did find that most of the variance (60%) was due to random analytic error and that there was no correlation between the dilution space ratio and age or body fat. However, in contrast to recent reports we found no evidence of a gender difference. Use of the constant dilution space ratio of 1.034 to recalculate CO2 product in published validation studies demonstrated improved accuracy, and thus the value of 1.034 is suggested for use in future studies.

Western lifestyles differ markedly from those of our hunter-gatherer ancestors, and these differences in diet and activity level are often implicated in the global obesity pandemic. However, few physiological data for hunter-gatherer populations are available to test these models of obesity. In this study, we used the doubly-labeled water method to measure total daily energy expenditure (kCal/day) in Hadza hunter-gatherers to test whether foragers expend more energy each day than their Western counterparts. As expected, physical activity level, PAL, was greater among Hadza foragers than among Westerners. Nonetheless, average daily energy expenditure of traditional Hadza foragers was no different than that of Westerners after controlling for body size. The metabolic cost of walking (kcal kg−1 m−1) and resting (kcal kg−1 s−1) were also similar among Hadza and Western groups. The similarity in metabolic rates across a broad range of cultures challenges current models of obesity suggesting that Western lifestyles lead to decreased energy expenditure. We hypothesize that human daily energy expenditure may be an evolved physiological trait largely independent of cultural differences.

Background: Bone loss often accompanies weight loss induced by caloric restriction (CR), but whether bone loss accompanies similar weight loss induced by exercise (EX) is unknown. We tested the hypothesis that EXinduced weight loss is associated with less bone loss compared with CR-induced weight loss. Methods: Forty-eight adults (30 women; 18 men; mean±SD age, 57±3 years; and mean±SD body mass index, 27±2 kg/m 2) were randomized to 1 of 3 groups for 1 year: CR group (n = 19), regular EX group (n=19), or a healthy lifestyle (HL) control group (n = 10). Primary outcome measure was change in hip and spine bone mineral density (BMD). Secondary outcomes were bone markers and hormones. Results: Body weight decreased similarly in the CR and EX groups (10.7% ± 6.3% [−8.2 ± 4.8 kg] vs 8.4%±6.3% [−6.7±5.6 kg]; P = .21), whereas weight did not change in the HL group (−1.2% ± 2.5% [−0.9 ± 2.0 kg]). Compared with the HL group, the CR group had decreases in BMD at the total hip (−2.2% ± 3.1% vs 1.2% ± 2.1%; P=.02) and intertrochanter (−2.1%±3.4% vs 1.7±2.8%; P = .03). The CR group had a decrease in spine BMD (−2.2%±3.3%; P=.009). Despite weight loss, the EX group did not demonstrate a decrease in BMD at any site. Body weight changes correlated with BMD changes in the CR (R=0.61; P =.007) but not in the EX group. Bone turnover increased in both CR and EX groups. Conclusions: CR-induced weight loss, but not EXinduced weight loss, is associated with reductions in BMD at clinically important sites of fracture. These data suggest that EX should be an important component of a weight loss program to offset adverse effects of CR on bone.

No abstract

Weight loss induced by exercise training or calorie restriction improves glucose tolerance and insulin action in nonobese, healthy, middle-aged men and women. However, it does not appear that exercise training-induced weight loss results in greater improvements than those that result from calorie restriction alone.

Evidence has shown that ubiquitin proteasome system (UPS) impairment plays an important role in the dopamine (DA) neurodegeneration in Parkinson's disease (PD). It has been reported that application of proteasomal inhibitor lactacystin in ventral mesencephalon (VM) cultures can cause DA neurodegeneration, although the underlying mechanisms are not clear. Herein, we used the lactacystin-induced DA cell degeneration model to study the neuroprotection of glial cellderived neurotrophic factor (GDNF) in VM cultures. We measured the expression of endoplasmic reticulum stress (ERS)-related genes, and determined the caspase-3 activation, apoptotic cell death, as well as a-synuclein-positive inclusions in DA neurons. We found that GDNF treatment significantly suppressed the expression of ERS-related genes and inhibited the activation of caspase-3 and apoptotic cell death without affecting a-synuclein-positive inclusions in DA neurons. Our study suggests that the protection of GDNF against DA neurodegeneration in the UPS impairment model is associated with ERS and caspase-3 suppression.