Publications

CONTEXT

The increasing prevalence of obesity is a major public health concern. Physical activity may promote weight and body fat loss.

OBJECTIVE

To examine the effects of exercise on total and intra-abdominal body fat overall and by level of exercise.

DESIGN

Randomized controlled trial conducted from 1997 to 2001.

SETTING AND PARTICIPANTS

A total of 173 sedentary, overweight (body mass index > or =24.0 and >33% body fat), postmenopausal women aged 50 to 75 years who were living in the Seattle, Wash, area.

INTERVENTION

Participants were randomly assigned to an intervention consisting of exercise facility and home-based moderate-intensity exercise (n = 87) or a stretching control group (n = 86).

MAIN OUTCOME MEASURE

Changes in body weight and waist and hip circumferences at 3 and 12 months; total body, intra-abdominal, and subcutaneous abdominal fat at 12 months.

RESULTS

Twelve-month data were available for 168 women. Women in the exercise group participated in moderate-intensity sports/recreational activity for a mean (SD) of 3.5 (1.2) d/wk for 176 (91) min/wk. Walking was the most frequently reported activity. Exercisers showed statistically significant differences from controls in baseline to 12-month changes in body weight (-1.4 kg; 95% confidence interval [CI], -2.5 to -0.3 kg), total body fat (-1.0%; 95% CI, -1.6% to -0.4%), intra-abdominal fat (-8.6 g/cm2; 95% CI, -17.8 to 0.9 g/cm2), and subcutaneous abdominal fat (-28.8 g/cm2); 95% CI, -47.5 to -10.0 g/cm2). A significant dose response for greater body fat loss was observed with increasing duration of exercise.

CONCLUSIONS

Regular exercise such as brisk walking results in reduced body weight and body fat among overweight and obese postmenopausal women.

OBJECTIVES

To determine whether the failure of the orexigenic hormone ghrelin to increase as it normally does with weight loss contributes to impaired weight recovery in older persons.

DESIGN

Prospective diet intervention study.

SETTING

University of Washington Medical Center from 2001 through 2005.

PARTICIPANTS

Twenty-one younger (18-35) and 18 older (> or =70) men and women.

INTERVENTION

Two weeks of a weight-maintaining diet were followed in sequence by 2 weeks of 30% calorie restriction, then 4 weeks of ad libitum food intake.

MEASUREMENTS

Twenty-four-hour plasma ghrelin levels, dual x-ray absorptiometry scan for body composition, resting energy expenditure, and calorie intakes were measured.

RESULTS

Both younger and older subjects lost weight with calorie restriction and failed to fully regain their baseline weight. The older adults trended toward increasing their calorie intake above their baseline level during the ad libitum period (111+/-66 kcal, P=.11), whereas the younger individuals did not (-236+/-95 kcal, P=.02). There was no statistically significant difference between the two cohorts in 24-hour ghrelin levels before or after calorie restriction. Ghrelin levels in the two cohorts increased equivalently after calorie restriction and decreased after ad libitum food consumption resumed.

CONCLUSION

Ghrelin levels in healthy older individuals respond appropriately in a compensatory manner to changes in body weight and calorie intake.

The purpose of this study was to determine the relationship between plasma C-reactive protein (CRP) and body mass index (BMI) in elderly Korean men. A review of routine health examination records were done. Out of 671 eligible elderly men, who had their routine health examination in 2001 at a Health Promotion Center of a university hospital, 367 subjects were included after excluding inflammatory conditions. Subgroup analyses were performed on those who did not smoke and exercised regularly. Body composition, blood pressure, blood samples and radiologic examinations including chest radiography and abdominal ultrasound were obtained from each subject. Age, BMI, current smoking, regular exercise, WBC count, HDL-cholesterol, gamma glutamyl transferase were independently associated with logCRP. BMI subgroups according to the Asia-Pacific guideline did not show any difference in CRP level from each other by ANCOVA (p>0.05). However, BMI groups subdivided according to our criteria showed an association with CRP; the CRP level was lowest in the group of BMI between 18.5-19.4 and showed significant difference from BMI group of the highest BMI group (>or=29.0). Since elevated CRP levels are associated with higher risk for cardiovascular disease, lower BMI (18.5-19.4) levels may be advised for healthy elderly men in Korea.

CONTEXT

The expression of adipogenic genes in sc adipose tissue has been reported to be lower among patients with HIV-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy.

OBJECTIVE

The objective of the study was to investigate the temporal relationships among changes in adipogenic gene expression in sc adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy.

DESIGN

This was a prospective longitudinal study.

SETTING

The study was conducted at HIV clinics in Seattle, Washington.

PARTICIPANTS

The study population included 31 HIV-infected and 12 control subjects.

INTERVENTIONS

Subjects were followed up for 12 months after they initiated or modified their existing antiretroviral regimen.

MAIN OUTCOME MEASURES

Changes in body composition, plasma lipids, insulin sensitivity, and gene expression in sc abdominal and thigh adipose tissue.

RESULTS

Subjects who developed lipoatrophy (n=10) had elevated fasting triglycerides [3.16 (sd 2.79) mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv glucose tolerance test [1.89 (sd 1.27)x10(-4) min(-1)/microU.ml] after 12 months, whereas those without lipoatrophy (n=21) did not show any metabolic complications [triglycerides 1.32 (sd 0.58) mmol/liter, P=0.01 vs. lipoatrophy; insulin sensitivity 3.52 (sd 1.91)x10(-4) min(-1)/microU.ml, P=0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2-month visit, several months before any loss of extremity fat mass was evident.

CONCLUSIONS

In HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance and might be caused by a direct or indirect effect of antiretroviral drugs on sc adipocyte differentiation.

Optimizing duration of participation in health promotion programs has important implications for program reach and costs. We examined data from 355 participants in EnhanceWellness (EW) to determine whether improvements in disability risk factors (depression, physical inactivity) occurred early or late in the enrollment period. Participants had a mean age of 74 years; 76% were women, and 16% were non-white. The percent depressed declined from enrollment to six months (35% to 28%, p = .001) and from six to 12 months (28% to 22%, p = .03). The percent physically inactive declined over the first six months, without substantial change thereafter (47%, 29%, and 29%). Those remaining inactive at six months had worse self-rated health and more depressive symptoms initially; a subset of those increased their physical activity by 12 months. These data suggest that enrollment could be reduced from 12 to six months without compromising favorable effects of EW participation, although additional benefits may accrue beyond six months.

Previous studies have shown that COPD adversely affects distant organs and body systems, including the brain. This pilot study aims to model the relationships between respiratory insufficiency and domains related to brain function, including low mood, subtly impaired cognition, systemic inflammation, and brain structural and neurochemical abnormalities. Nine healthy controls were compared with 18 age- and education-matched medically stable-COPD patients, half of whom were oxygen-dependent. Measures included depression, anxiety, cognition, health status, spirometry, oximetry at rest and during 6-minute walk, and resting plasma cytokines and soluble receptors, brain MRI, and MR spectroscopy in regions relevant to mood and cognition. ANOVA was used to compare controls with patients and with COPD subgroups (oxygen users [n = 9] and nonusers [n = 9]), and only variables showing group differences at p < or = 0.05 were included in multiple regressions controlling for age, gender, and education to develop the final model. Controls and COPD patients differed significantly in global cognition and memory, mood, and soluble TNFR1 levels but not brain structural or neurochemical measures. Multiple regressions identified pathways linking disease severity with impaired performance on sensitive cognitive processing measures, mediated through oxygen dependence, and with systemic inflammation (TNFR1), related through poor 6-minute walk performance. Oxygen desaturation with activity was related to indicators of brain tissue damage (increased frontal choline, which in turn was associated with subcortical white matter attenuation). This empirically derived model provides a conceptual framework for future studies of clinical interventions to protect the brain in patients with COPD, such as earlier oxygen supplementation for patients with desaturation during everyday activities.

Unintentional weight loss may occur spontaneously in older humans and animals. Further weight losses after surgery or illness in the older patients result in increased morbidity, mortality, and hospital readmission rate. A growing body of work has shown increased appetite and weight gain in response to administration of ghrelin, the "hunger hormone." We conducted two studies in senescent male Brown Norway rats to assess the ability of peripheral administration of ghrelin to increase body weight and food intake. One study assessed the effect of 2 wk of daily subcutaneous ghrelin administration (1 mg.kg(-1).day(-1)) to senescent rats in a baseline condition; a second study used the same administration protocol in an interventional experiment with aged rats subjected to a surgery with 10-15% blood loss as a model of elective surgery. In both studies, animals receiving ghrelin maintained their body weights, whereas control animals lost weight. Body weight stability was achieved in ghrelin-treated animals despite a lack of increase in daily or cumulative food intake in both experiments. Hormone and proinflammatory cytokine levels were measured before surgery and after 14 days of treatment. Ghrelin treatment appeared to blunt declining ghrelin levels and also to blunt cytokine increases seen in the surgical control group. The ability of peripheral ghrelin treatment to maintain body weights of senescent rats without concomitant increases in food intake may be due to its known ability to decrease sympathetic activity and metabolic rate, perhaps by limiting cytokine-driven inflammation.

In the event of a radiation accident or attack, it will be imperative to quickly assess the amount of radiation exposure to accurately triage victims for appropriate care. RNA-based radiation dosimetry assays offer the potential to rapidly screen thousands of individuals in an efficient and cost-effective manner. However, prior to the development of these assays, it will be critical to identify those genes that will be most useful to delineate different radiation doses. Using global expression profiling, we examined expression changes in nonimmortalized T cells across a wide range of doses (0.15-12 Gy). Because many radiation responses are highly dependent on time, expression changes were examined at three different times (3, 8, and 24 h). Analyses identified 61, 512 and 1310 genes with significant linear dose-dependent expression changes at 3, 8 and 24 h, respectively. Using a stepwise regression procedure, a model was developed to estimate in vitro radiation exposures using the expression of three genes (CDKN1A, PSRC1 and TNFSF4) and validated in an independent test set with 86% accuracy. These findings suggest that RNA-based expression assays for a small subset of genes can be employed to develop clinical biodosimetry assays to be used in assessments of radiation exposure and toxicity.