Project description:Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPAR?-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65-79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m(2)) and women (n = 40, BMI = 33.3 ± 4.9 kg/m(2)) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (-1,160 vs. -647 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: -43 vs. -88 cm(3), P = 0.005; women: -34 vs. -59 cm(3), P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.
Project description:ObjectiveWeight loss among metabolically healthy obese (MHO) individuals may be unnecessary or result in elevated cardio-metabolic risk. We studied the effects of exercise- or diet-induced weight loss on cardio-metabolic risk among MHO and metabolically abnormal obese (MAO) adults.Research design and methodsParticipants were 63 MHO and 43 MAO adults who took part in 3 to 6 months of exercise- or diet-induced weight loss intervention. Changes in anthropometry, adipose tissue distribution, and cardio-metabolic risk factors were assessed.ResultsBody weight, waist circumference, and total abdominal and visceral adipose tissue were reduced in all subjects (P < 0.05). Improvements in insulin sensitivity were observed in MHO and MAO men and women (P < 0.05), but were greater in the MAO individuals (P < 0.05). Fasting insulin was the only other cardio-metabolic improvement among MHO individuals (P < 0.05).ConclusionsLifestyle-induced weight loss among MHO subjects is associated with a reduction in total and abdominal obesity and improvement in selected cardio-metabolic risk factors.
Project description:Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Using a high-density antibody array, we assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized double-blinded crossover trial of 44 healthy non-smoking men and women, aged 21-45 years. The plasma proteome was analyzed on an antibody microarray with ~3,300 full-length antibodies, printed in triplicate. Moderated paired t-tests were performed on individual antibodies, and gene-set analyses were performed based on KEGG and GO pathways. Among the 3,000 antibodies analyzed, statistically significant differences in plasma protein levels were observed for nine antibodies after adjusting for false discoveries (FDR adjusted p-value<0.1). The most significant protein was succinate dehydrogenase subunit C (SDHC), a key enzyme complex of the mitochondrial tricarboxylic acid (TCA) cycle. The other statistically significant proteins (NR2F1, MSI1, MYH1, FOXO1, KHDRBS3, NFKBIE, LYZ and IKZF1) are involved in multiple pathways, including DNA base-pair repair, inflammation and oncogenic pathways. None of the 258 KEGG and 1,139 GO pathways was found to be statistically significant after FDR adjustment. This study suggests several chemopreventive mechanisms of aspirin in humans, which have previously been reported to play a role in anti- or pro-carcinogenesis in cell systems; however, larger, confirmatory studies are needed.
Project description:Compared with young adults, older adults have significantly impaired capacities to resist oxidative damage when faced with acute stress such as ischemia/reperfusion. This impairment likely contributes to increased morbidity and mortality in older adults in response to acute trauma, infections, and the susceptibility to diseases such as atherosclerosis, cancer, diabetes, and Alzheimer's disease. Consumption of foods high in polyphenols, particularly anthocyanins, have been associated with improved health, but the mechanisms contributing to these salutary effects remain to be fully established. This study tested the hypothesis that consumption of tart cherry juice containing high levels of anthocyanins improves the capacity of older adults to resist oxidative damage during acute oxidative stress. In a double-blind, placebo-controlled, crossover design, 12 volunteers [6 men and 6 women; age 69 +/- 4 y (61-75 y)] consumed in random order either tart cherry juice or placebo (240 mL twice daily for 14 d) separated by a 4-wk washout period. The capacity to resist oxidative damage was measured as the changes in plasma F(2)-isoprostane levels in response to forearm ischemia-reperfusion (I/R) before and after each treatment. The tart cherry juice intervention reduced the I/R-induced F(2)-isoprostane response (P < 0.05), whereas placebo had no significant effect. The tart cherry juice intervention also reduced basal urinary excretion of oxidized nucleic acids (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine) (P < 0.05) but not urinary excretion of isoprostanes. These data suggest that consumption of tart cherry juice improves antioxidant defenses in vivo in older adults as shown by an increased capacity to constrain an oxidative challenge and reduced oxidative damage to nucleic acids.
Project description:Depressive symptoms are associated with increased risk for cardiovascular disease (CVD), and inflammation may contribute to this relationship. Pericardial fat, a highly metabolically active fat depot, is implicated in the pathogenesis of CVD, but its association with depressive symptoms is unclear. This study examined the cross-sectional and longitudinal association between depressive symptoms and pericardial fat over a three-year period. Participants were 543 healthy men and women (mean age = 62.9 years) without history or objective signs of coronary heart disease from the Whitehall II cohort. In men, depressive symptoms were positively associated with pericardial fat at baseline after adjustment for sociodemographics, waist to hip ratio and conventional cardiovascular risk factors. Inflammation, indexed by plasma interleukin 6 concentration, accounted for 17% of this association. Longitudinally, depressive symptoms did not predict pericardial fat three years later in men once baseline levels of pericardial fat were accounted for. No significant associations between depressive symptoms and pericardial fat were found in women. Overall, our findings suggest that greater pericardial fat might be a mechanism by which depressive symptoms are associated with increased risk for CVD in men, and inflammation may also lie on this pathway.
Project description:Treatment with mirtazapine, a widely prescribed antidepressant, has been linked to weight gain and dyslipidemia. Whether dyslipidemia occurs secondary to increased appetite due to antidepressant treatment, or due to direct pharmacological effects of mirtazapine is unknown. The aim of this analysis is to complement our previously published results of the effect of mirtazapine on metabolism and energy substrate partitioning from a proof-of-concept, open-label clinical study (ClinicalTrials.gov NCT00878540) in 12 healthy males (20-25 years). We report the effect of a seven-day administration of mirtazapine 30 mg per day on weight and lipid metabolism in healthy men under highly standardized conditions with respect to diet, physical activity and day-night-rhythm and under continuous clinical observation. After a 7-day administration of mirtazapine 30 mg, we observed a statistically significant increase in triglyceride levels (mean change + 4.4 mg/dl; 95% CI [- 11.4; 2.6]; p = 0.044) as well as TG/HDL-C ratio (mean change + 0.2; 95% CI [- 0.4; 0.1]; p = 0.019) and a decrease in HDL-cholesterol (mean change - 4.3 mg/dl; 95% CI [2.1; 6.5]; p = 0.004), LDL-cholesterol (mean change - 8.7 mg/dl; 95% CI [3.8; 13.5]; p = 0.008), total cholesterol (mean change - 12.3 mg/dl; 95% CI [5.4; 19.1]; p = 0.005), and non-HDL-C (mean change - 8.0 mg/dl; 95% CI [1.9; 14.0]; p = 0.023). Notably, weight (mean change - 0.6 kg; 95% CI [0.4; 0.8]; p = 0.002) and BMI (mean change - 0.2; 95% CI [0.1; 0.2]; p = 0.002) significantly decreased. No change in waist circumference (mean change - 0.4 cm; 95% CI [- 2.1; 2.9]; p = 0.838) or waist-to-hip-ratio (mean change 0.0; 95% CI [- 0.0; 0.0]; p = 0.814) was observed. This is the first study showing unfavorable changes in lipid metabolism under mirtazapine in healthy individuals despite highly standardized conditions including dietary restriction, and despite the observation of a decrease of weight. Our findings support the hypothesis that mirtazapine has direct pharmacological effects on lipid metabolism. ClinicalTrials.gov: NCT00878540.
Project description:Women with body weight dissatisfaction (BWD) have long-term negative assessments of their body weight, which are often associated with poor eating behavior. In this study, we investigated the effect of body-related information on the food cue processing and attention of women with BWD. Sixty-eight women were recruited and assigned to either a BWD (NPSS-F > 2) (n = 32) or a no body weight dissatisfaction (NBWD) group (NPSS-F < 1) (n = 36). We measured attentional bias to food cues (high- and low-calorie) with a food probe task after exposure to body-related information and recorded eye tracking data. Body-related images were presented prior to a pair of stimulus images (food-neutral or neutral-neutral). Body-related information and food type were repeated measure factors in our study. Our results showed that the first fixation duration bias for high-calorie foods was significantly longer than for low-calorie foods after exposure to overweight cues in the BWD group. Compared with the NBWD group, the BWD group showed longer first fixation duration bias for high-calorie foods after exposure to overweight cues. The direction for high-calorie foods was significantly more often than that for low-calorie foods in the BWD group after exposure to body-related information. Our findings suggest that compared to women with NBWD, women with BWD may be more susceptible to body-related information, resulting in increased attention to high-calorie foods.
Project description:How different measures of adiposity are similarly or differentially related to mobility limitation and mortality is not clear. In total, 5849 community-dwelling men aged ≥65 years (mean age: 72 years) were followed mortality over 10 years and self-reported mobility limitations (any difficulty walking 2-3 blocks or with climbing 10 steps) at six contacts over 14 years. Baseline measures of adiposity included weight, BMI and percent fat by DXA. Appendicular lean mass (ALM, by DXA) was analyzed as ALM/ht2. Proportional hazards models estimated the risk of mortality, and repeated measures generalized estimating equations estimated the likelihood of mobility limitation. Over 10 years, 27.9% of men died; over 14 years, 48.0% of men reported at least one mobility limitation. We observed U-shaped relationships between weight, BMI, percent fat and ALM/ht2 with mortality. There was a clear log-linear relationship between weight, BMI and percent fat with incident mobility limitation, with higher values associated with a greater likelihood of mobility limitation. In contrast, there was a U-shaped relationship between ALM/ht2 and incident mobility limitation. These observational data suggest that no single measure of adiposity or body composition reflects both the lowest risk of mortality and the lowest likelihood for developing mobility limitation in older men.
Project description:Abdominal subcutaneous adipose tissue transcriptomes were analyzed between 11 young and 8 elderly obese men during a lifestyle intervention. Lifestyle intervention: Individuals underwent 8-weeks of calorie-restriction of 20% below their daily energy requirement aerobic combined to two sessions of resistance exercise per weeks.
Project description:Vastus lateralis Skeletal muscle transcriptomes were analyzed between 13 young and 12 elderly obese men during a lifestyle intervention. Lifestyle intervention: Individuals underwent 8-weeks of calorie-restriction of 20% below their daily energy requirement aerobic combined to two sessions of resistance exercise per weeks.