Rudy J. Valentine

A high protein moderate carbohydrate diet fed at discrete meals reduces early progression of N-methyl-N-nitrosourea-induced breast tumorigenesis in rats

Breast cancer is the most prevalent cancer in American women. Dietary factors are thought to have a strong influence on breast cancer incidence. This study utilized a meal-feeding protocol with female Sprague-Dawley rats to evaluate effects of two ratios of carbohydrate:protein on promotion and early progression of breast tissue carcinomas. Mammary tumors were induced by N-methyl-N-nitrosourea (MNU) at 52 d of age. Post-induction, animals were assigned to consume either a low protein high carbohydrate diet (LPHC; 15% and 60% of energy, respectively) or a high protein moderate carbohydrate diet (HPMC; 35% and 40% of energy, respectively) for 10 wk. Animals were fed 3 meals/day to mimic human absorption and metabolism patterns. The rate of palpable tumor incidence was reduced in HPMC relative to LPHC (12.9 ± 1.4%/wk vs. 18.2 ± 1.3%/wk). At 3 wk, post-prandial serum insulin was larger in the LPHC relative to HPMC (+136.4 ± 33.1 pmol/L vs. +38.1 ± 23.4 pmol/L), while at 10 wk there was a trend for post-prandial IGF-I to be increased in HPMC (P = 0.055). There were no differences in tumor latency, tumor surface area, or cumulative tumor mass between diet groups. The present study provides evidence that reducing the dietary carbohydrate:protein ratio attenuates the development of mammary tumors. These findings are consistent with reduced post-prandial insulin release potentially diminishing the proliferative environment required for breast cancer tumors to progress.

Effects of exercise and low-fat diet on adipose tissue inflammation and metabolic complications in obese mice

Adipose tissue inflammation causes metabolic disturbances, including insulin resistance and hepatic steatosis. Exercise training (EX) may decrease adipose tissue inflammation, thereby ameliorating such disturbances, even in the absence of fat loss. The purpose of this study was to 1) compare the effects of low-fat diet (LFD), EX, and their combination on inflammation, insulin resistance, and hepatic steatosis in high-fat diet-induced obese mice and 2) determine the effect of intervention duration (i.e., 6 vs. 12 wk). C57BL/6 mice (n = 109) fed a 45% fat diet (HFD) for 6 wk were randomly assigned to an EX (treadmill: 5 days/wk, 6 or 12 wk, 40 min/day, 65-70% Vo(2max)) or sedentary (SED) group. Mice remained on HFD or were placed on a 10% fat diet (LFD) for 6 or 12 wk. Following interventions, fat pads were weighed and expressed relative to body weight; hepatic steatosis was assessed by total liver triglyceride and insulin resistance by HOMA-IR and glucose AUC. RT-PCR was used to determine adipose gene expression of MCP-1, F4/80, TNF-alpha, and leptin. By 12 wk, MCP-1, F4/80, and TNF-alpha mRNA were reduced by EX and LFD. Exercise (P = 0.02), adiposity (P = 0.03), and adipose F4/80 (P = 0.02) predicted reductions in HOMA-IR (r(2) = 0.75, P < 0.001); only adiposity (P = 0.04) predicted improvements in hepatic steatosis (r(2) = 0.51, P < 0.001). Compared with LFD, EX attenuated increases in adiposity, hepatic steatosis, and adipose MCP-1 expression from 6 to 12 wk. There are unique metabolic consequences of a sedentary lifestyle and HFD that are most evident long term, highlighting the importance of both EX and LFD in preventing obesity-related metabolic disturbances.

Sex impacts the relation between body composition and physical function in older adults.

Objective: To determine the sex-specific relationships between physical activity, aerobic fitness, adiposity (%Fat), mineral-free lean mass (MFLM), and balance and gait performance in older adults. Methods: Eighty-five female and 49 male sedentary, healthy, community-dwelling older adults (mean [SD] age, 69.6 [5.4] and 70.3 [4.7] years, respectively) were evaluated on habitual physical activity via questionnaire, aerobic fitness by a maximal oxygen consumption treadmill test, whole and regional body composition by dual-energy x-ray absorptiometry, and lower extremity physical function using gait tasks and computerized dynamic posturography. Results: As expected, men had less body fat, more lean mass, and higher aerobic fitness than did women and tended to perform better on all lower extremity physical function tasks (all P ≤ 0.1). Physical activity was not related to gait; however, fitness was related to gait in both sexes (r > 0.50, all P < 0.05). Body fat was related to gait in women (r = −0.38, P < 0.05) but not in men. Neither fitness nor body composition was related to balance in men, whereas in women, leg MFLM was positively associated (r = 0.27, P < 0.05). Women, but not men, with a greater ratio of body weight to leg MFLM performed worse on gait tasks (P < 0.001). There was an interaction with sex for %Fat on gait (P = 0.05) and for leg MFLM on balance (P < 0.05). Conclusions: In sedentary healthy older adults, the relation between body composition, aerobic fitness, and balance and gait differs between sexes such that women are more strongly affected by alterations in body composition. Lower %Fat and preservation of lower body lean mass have important implications for reducing the risk of physical disability, especially in older women.

Sex differences in the relationship between obesity, C-reactive protein, physical activity, depression, sleep quality and fatigue in older adults

Fatigue is a serious health concern in the elderly. Sex differences exist in adiposity, systemic inflammation, physical activity/fitness and fatigue; however, the relations among these variables remain inadequately characterized impeding the development of fatigue prevention strategies. Measures of adiposity, C-reactive protein, physical activity, aerobic fitness, fatigue, sleep quality and depression were obtained from 127 community-dwelling older adults. Although similar in age (70 y) and BMI (28.0kg/m(2)) women (n=80) reported 63% greater fatigue than men (p=0.04). Adiposity (r=0.44), CRP (r=0.29), physical activity (r=-0.26) and fitness (r=-0.41) were related to fatigue in women (all p<0.05), but not in men. Depression was also related to fatigue in women (r=0.37), and was the only variable related to fatigue in men (r=0.42). In women, fatigue was independently explained (all p<0.05) by CRP (6.6%), depression (6.3%), physical activity (5.8%), and adiposity (3.9%); however, in men, only depression explained variance in fatigue (12.0%). CRP was 40% higher and adiposity 12% higher in women reporting fatigue compared to those with no fatigue; no such differences existed in men. Obese women perceived a greater degree of fatigue than non-obese women, but this was not the case in men. Women report more fatigue than men which was independently associated with inflammation, depression, physical activity and adiposity, whereas in men the only independent predictor was depression. Strategies to prevent fatigue may differ in older women and men, especially with regard to inflammation, physical activity and adiposity.

Associations of visceral adiposity and exercise participation with C-reactive protein, insulin resistance, and endothelial dysfunction in Korean healthy adults

The aim of the current study was to examine the associations of visceral adiposity and exercise participation with C-reactive protein (CRP), insulin resistance, and endothelial dysfunction in Korean adults selected from the general population. We studied 160 Korean adults (aged 41.3 +/- 13.0 years; n = 38 men and n = 122 women) who volunteered in a health promotion program. Subjects were divided into 2 groups based upon spontaneous exercise participation for using a cross-sectional approach. We measured anthropometric factors (body mass index [BMI], percentage body fat, waist-hip ratio [WHR], and abdominal fat area by computed tomographic scanning), blood pressure (BP), blood levels of glucose, lipids, fibrinogen, CRP, leptin, hemoglobin A(1c), homeostasis model assessment (HOMA), and carotid intima media thickness (IMT; via ultrasonography). Associations among the variables were assessed by Pearson partial correlation and linear regression, controlling for age and sex. Independent t tests were used to assess differences between exercise participants and nonparticipants. Significance was accepted at P < .05. As expected, the measures of adiposity (BMI, percentage body fat, WHR, abdominal fat area) were highly correlated with each other (r = .49-.86, P < .01). Blood levels of high-sensitivity CRP (hsCRP), leptin, and HOMA were modestly correlated with all measures of adiposity. Visceral fat area was the most important predictor of hsCRP, explaining 19.6% of the variance using stepwise linear regression analysis (P < .01). As visceral fat area tertiles increased from low to high, a significant stepwise increment in blood levels of CRP (P < .001), HOMA (P = .005), and left carotid IMT (P = .035) was observed. However, hsCRP and HOMA were not significantly different when compared across whole-body fat tertiles. Systolic BP, diastolic BP, and left carotid IMT were modestly correlated with WHR and visceral fat area (P < .05); but systolic BP and diastolic BP were also correlated with BMI and percentage body fat (P < .05). Therefore, the relative importance of central adiposity as opposed to total body fatness in endothelial dysfunction is unclear. Compared with the nonexercise group, exercise participants had significantly lower (P < .05) WHR, visceral fat area, ratio of visceral fat area to subcutaneous area, hsCRP, hemoglobin A(1c), and HOMA, with no significant differences in BMI, percentage body fat, and physical fitness. Central obesity with high visceral fat is strongly associated with blood level of hsCRP, insulin resistance, and endothelial dysfunction-related factors in healthy Korean adults. In addition, exercise participation, even in the absence of difference in physical fitness, may be protective against development of central obesity and insulin resistance in this understudied Korean population.

Body composition assessment in athletes with spinal cord injury: comparison of field methods with dual-energy X-ray absorptiometry

Study design:Cross-sectional.Objectives:To compare relative body fatness (%Fat) estimates from field methods (skinfold thickness measurement (SKF) and bioelectrical impedance analysis (BIA)) with measures by dual-energy X-ray absorptiometry (DXA).Setting:University of Illinois, Urbana-Champaign, IL, USA.Methods:Field methods used both three- and seven-site SKF prediction equations and BIA generalized, spinal cord injury (SCI)-specific and athlete-specific equations. DXA was used as the reference method. College-aged varsity athletes with SCI (women=8, men=8; time since injury 16.2±5.7 years; injury level range T5–L5) were recruited.Results:Mean BMI was 20.8±2.6 and 22.5±2.1 kg m−2, and mean DXA %Fat was 31.9±3.8 and 20.6±8.4%, for women and men, respectively. All field methods under-predicted the %Fat when compared with DXA (ranges in mean differences: SKF women 2.9–8.2%, SKF men 6.9–12.4%; BIA women 0.5–3.9%, BIA men 0.3–7.0%). None of the field methods accurately predicted the %Fat compared with DXA (total error (TE): SKF women 7.4–12.1%, SKF men 8.4–15.2%; BIA women 5.1–9.3%, BIA men 6.7–10.7%). Of the SKF and BIA prediction equations, Evans et al.s three-site SKF (r=0.95, P<0.001, standard error of the estimate (SEE)=2.8 %Fat) prediction equation provided the best fit for this population.Conclusion:Further studies with larger samples are necessary to develop appropriate prediction equations for field methods in the athletic SCI population.

Effects of Diet and Exercise on Metabolic Disturbances in High Fat Diet-Fed Mice

Consumption of a high-fat diet (HFD) is associated with white adipose tissue (WAT) inflammation, which contributes to key components of the metabolic syndrome, including insulin resistance (IR) and hepatic steatosis (HS). To determine the differential effects of exercise training (EX), low-fat diet (LFD), and their combination on WAT inflammation, Balb/cByJ male mice (n=34) were fed an HFD for 12 wks before they were randomized into one of four intervention groups: HFD-EX, LFD-EX, HFD-sedentary (SED), or LFD-SED. EX mice performed 12 wks of exercise training on a motorized treadmill (1h/d, 5d/wk, 12 m/min, 5% grade, approximately 65% VO(2) max), while SED mice remained sedentary in their home cages. WAT gene expression of adipokines was assessed using rt-PCR. IR was measured using HOMA-IR, and HS via hepatic triglyceride content. EX significantly reduced (53%) WAT gene expression of MCP-1, and LFD significantly reduced (50%) WAT gene expression of the macrophage specific marker, F4/80 as well as the adipocytokine IL-1 ra (25%). EX independently improved IR, while both EX and LFD improved HS. These findings suggest that both diet and exercise have unique beneficial effects on WAT inflammatory markers and the mechanism by which each treatment improves metabolic complications associated with chronic consumption of an HFD may be different.

Reduction in trunk fat predicts cardiovascular exercise training-related reductions in C-reactive protein

C-reactive protein (CRP) is an independent risk factor for cardiovascular disease. We sought to determine (1) if 10 months of cardiovascular exercise training (Cardio) reduces CRP in a group of older adults, (2) if such a reduction is related to improvements in trunk fat, fitness, and/or psychosocial variables, and (3) if the effect of Cardio on CRP differs between men and women. Community-dwelling residents (n=127; 60-83 yrs) were randomized to a Flex group (n=61) where they participated in 2-75 min supervised sessions per wk during which they performed non-cardiovascular flexibility and balance exercises or a Cardio group (n=66) where they participated in three supervised sessions per wk during which they performed cardiovascular exercises for approximately 45-60 min at 60-70% maximal oxygen uptake. The main outcome measures were serum CRP, cardiovascular fitness, total and central adiposity, and self-reported psychosocial function. Cardio experienced a reduction in CRP (-0.5mg/L), as well as improvements in fitness (+7%) and total (-1.5%) and central (i.e., trunk) (-2.5%) adiposity. These relationships were not modified by sex. Regression analyses indicated that only the reduction in trunk fat was significantly related to the reduction in CRP. Ten months of cardiovascular exercise training reduced CRP in previously sedentary older adults and this effect was partially mediated by a reduction in trunk fat.

The associations of adiposity, physical activity and inflammation with fatigue in older adults.

Persistent feelings of fatigue are a widespread complaint reported by older adults, and are associated with detriments in health and quality of life. The aim of this study was to determine the influence of weight status, habitual physical activity and inflammation, after controlling for common psychosocial variables such as depression, on perceptions of fatigue in relatively healthy older adults. Older men and women (N=182, age=69.2±6.7 years, 98 men) were assessed for adiposity via dual-energy X-ray absorptiometry, physical activity (PA) using accelerometers, systemic inflammation [serum C-reactive protein (CRP), interleukin-6 (IL-6), sIL-6R and WBC count], fatigue according to the Multidimensional Fatigue Inventory (MFI), sleep using the Pittsburgh Sleep Quality Index (PSQI) and depression via the Geriatric Depression Scale (GDS). Men and women reported similar levels of fatigue in all dimensions (p>0.05) except women reported higher levels of mental fatigue than men (p=0.049). With the exception of mental fatigue, adiposity was positively, and physical activity was inversely associated with all other dimension of fatigue (r range=0.20-0.42, and -0.18 to -0.37, respectively). CRP, IL-6 and WBC were also related to several dimensions of fatigue (r range=0.15-0.26). Regression analyses revealed that after controlling for other factors, including depression and sleep quality, adiposity independently explained a significant amount of the variance in general and physical fatigue. In addition to depression and sleep quality, adiposity may represent a potential target for reducing fatigue in older adults.

The association between regional body composition and metabolic outcomes in athletes with spinal cord injury

Study design:Cross-sectional study comparing athletes with spinal cord injury (SCI) and age and body mass index matched able-bodied controls (AB).Objective:To examine the impact of exercise training on the relation between whole body, regional and intermuscular adipose tissue (IMAT) and glucose tolerance, insulin action and lipid profile.Setting:University Research Laboratory, USA.Methods:Fourteen college-aged athletes with SCI (seven men; duration of injury 16.5±5.7 years, level of injury T5-L5) and 17 sedentary AB (eight men) were assessed for body composition via dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging. Insulin sensitivity index (ISI) was determined via 2-h oral glucose challenge; standard lipid profile was determined from fasting blood samples.Results:Although ISI was 30% higher in SCI, there were no significant differences between groups in glucose and insulin responses or in lipid measures. Adjusting for absolute and relative thigh IMAT area, fasting insulin (13.8±5.3 μIU, 16.3±5.6 μIU; P<0.05; SCI vs AB respectively) and ISI (4.0±1.4, 3.1±1.3; P<0.05) were significantly better among SCI athletes compared to AB. Measures of adiposity did not correlate with glucose response or most lipid measures. Within SCI and AB, respectively, ISI correlated strongly (all P<0.05) with absolute (r=−0.70, −0.54) and relative IMAT (r=−0.54, −0.50), than with trunk (r=−0.62, −0.64) and whole body fat mass (r=−0.61, −0.64).Conclusion:Habitual physical activity can maintain insulin sensitivity in SCI compared to sedentary AB controls. Total body fat mass, central adiposity and thigh IMAT appear to impact risk for metabolic disease in SCI individuals with IMAT playing a larger role in SCI than AB.