Jennifer Rood

Reduced Adipose Tissue Oxygenation in Human Obesity - Evidence for Rarefaction, Macrophage Chemotaxis and Inflammation without an Angiogenic Response

OBJECTIVE— Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation. RESEARCH DESIGN AND METHODS— Oxygen partial pressure (AT pO2) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay. RESULTS— AT pO2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO2 was negatively correlated with percent body fat (R = −0.50, P < 0.05). Compared with lean subjects, overweight/obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator–activated receptor γ1 and higher collagen VI mRNA expression, which correlated with AT pO2 (P < 0.05). Of clinical importance, AT pO2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α secretion (R = −0.58, R = −0.79, P < 0.05), suggesting that lower AT pO2 could drive AT inflammation in obesity. CONCLUSIONS— Adipose tissue rarefaction might lie upstream of both low AT pO2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity.

Accuracy of Armband Monitors for Measuring Daily Energy Expenditure in Healthy Adults

INTRODUCTION There is a need to develop accurate devices for measuring daily energy expenditure under free-living conditions, particularly given our current obesity epidemic. PURPOSE The purpose of the present study was to evaluate the validity of energy expenditure estimates from two portable armband devices, the SenseWear Pro3 Armband (SWA) monitor and the SenseWear Mini Armband (Mini) monitor, under free-living conditions. METHODS Participants in the study (30 healthy adults aged 24-60 yr) wore both monitors for 14 consecutive days, including while sleeping. Criterion values for total energy expenditure (TEE) were determined using doubly labeled water (DLW), the established criterion standard method for free-living energy expenditure assessment. RESULTS The average TEE estimates were within 112 kcal·d−¹ for the SWA and within 22 kcal·d−¹ for the Mini, but the absolute error rates (computed as the average absolute value of the individual errors) were similar for the two monitors (SWA = 8.1% ± 6.8%, Mini = 8.3% ± 6.5%). Using intraclass correlation (ICC) analysis, significant agreements were found between the SWA and DLW estimates of energy expenditure (ICC = 0.80, 95% CI = 0.89-0.70) and between the Mini and DLW (ICC = 0.85, 95% CI = 0.92-0.76). Graphical plots of the DLW TEE values against the difference between DLW and monitor estimates of TEE showed that the agreement was consistent across a range of TEE values. CONCLUSIONS The SenseWear Pro3 and the SenseWear Mini armbands show promise for accurately measuring daily energy expenditure under free-living conditions. However, more work is needed to improve the ability of these monitors to accurately measure energy expenditure at higher levels of expenditure.

Effect of Dietary Protein Content on Weight Gain, Energy Expenditure, and Body Composition During Overeating: A Randomized Controlled Trial

CONTEXT The role of diet composition in response to overeating and energy dissipation in humans is unclear. OBJECTIVE To evaluate the effects of overconsumption of low, normal, and high protein diets on weight gain, energy expenditure, and body composition. DESIGN, SETTING, AND PARTICIPANTS A single-blind, randomized controlled trial of 25 US healthy, weight-stable male and female volunteers, aged 18 to 35 years with a body mass index between 19 and 30. The first participant was admitted to the inpatient metabolic unit in June 2005 and the last in October 2007. INTERVENTION After consuming a weight-stabilizing diet for 13 to 25 days, participants were randomized to diets containing 5% of energy from protein (low protein), 15% (normal protein), or 25% (high protein), which they were overfed during the last 8 weeks of their 10- to 12-week stay in the inpatient metabolic unit. Compared with energy intake during the weight stabilization period, the protein diets provided approximately 40% more energy intake, which corresponds to 954 kcal/d (95% CI, 884-1022 kcal/d). MAIN OUTCOME MEASURES Body composition was measured by dual-energy x-ray absorptiometry biweekly, resting energy expenditure was measured weekly by ventilated hood, and total energy expenditure by doubly labeled water prior to the overeating and weight stabilization periods and at weeks 7 to 8. RESULTS Overeating produced significantly less weight gain in the low protein diet group (3.16 kg; 95% CI, 1.88-4.44 kg) compared with the normal protein diet group (6.05 kg; 95% CI, 4.84-7.26 kg) or the high protein diet group (6.51 kg; 95% CI, 5.23-7.79 kg) (P = .002). Body fat increased similarly in all 3 protein diet groups and represented 50% to more than 90% of the excess stored calories. Resting energy expenditure, total energy expenditure, and body protein did not increase during overfeeding with the low protein diet. In contrast, resting energy expenditure (normal protein diet: 160 kcal/d [95% CI, 102-218 kcal/d]; high protein diet: 227 kcal/d [95% CI, 165-289 kcal/d]) and body protein (lean body mass) (normal protein diet: 2.87 kg [95% CI, 2.11-3.62 kg]; high protein diet: 3.18 kg [95% CI, 2.37-3.98 kg]) increased significantly with the normal and high protein diets. CONCLUSIONS Among persons living in a controlled setting, calories alone account for the increase in fat; protein affected energy expenditure and storage of lean body mass, but not body fat storage. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00565149.

Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals

UNLABELLED Calorie restriction (CR) delays the development of age-associated disease and increases lifespan in rodents, but the effects in humans remain uncertain. PURPOSE Determine the effect of 6 months of CR with or without exercise on cardiovascular disease (CVD) risk factors and estimated 10-year CVD risk in healthy non-obese men and women. METHODS Thirty-six individuals were randomized to one of three groups for 6 months: Control, 100% of energy requirements; CR, 25% calorie restriction; CR+EX, 12.5% CR+12.5% increase in energy expenditure via aerobic exercise. CVD risk factors were assessed at baseline, 3 and 6 months. RESULTS After 6 months, CR and CR+EX lost approximately 10% of body weight. CR significantly reduced triacylglycerol (-31+/-15mg/dL) and factor VIIc (-10.7+/-2.3%). Similarly CR+EX reduced triacylglycerol (-22+/-8mg/dL) and additionally reduced LDL-C (-16.0+/-5.1mg/dL) and DBP (-4.0+/-2.1mmHg). In contrast, both triacylglycerol (24+/-14mg/dL) and factor VIIc (7.9+/-2.3%) were increased in the Control group. HDL-cholesterol was increased in all groups while hsCRP was lower in the Controls versus CR+EX. Estimated 10-year CVD risk significantly declined from baseline by 29% in CR (P<0.001) and 38% in the CR+EX (P<0.001) while remaining unchanged in the Control group. CONCLUSIONS Based on combined favorable changes in lipid and blood pressure, caloric restriction with or without exercise that induces weight loss favorably reduces risk for CVD even in already healthy non-obese individuals.

Metabolic Slowing with Massive Weight Loss despite Preservation of Fat-Free Mass

CONTEXT An important goal during weight loss is to maximize fat loss while preserving metabolically active fat-free mass (FFM). Massive weight loss typically results in substantial loss of FFM potentially slowing metabolic rate. OBJECTIVE Our objective was to determine whether a weight loss program consisting of diet restriction and vigorous exercise helped to preserve FFM and maintain resting metabolic rate (RMR). PARTICIPANTS AND INTERVENTION We measured body composition by dual-energy x-ray absorptiometry, RMR by indirect calorimetry, and total energy expenditure by doubly labeled water at baseline (n = 16), wk 6 (n = 11), and wk 30 (n = 16). RESULTS At baseline, participants were severely obese (× ± SD; body mass index 49.4 ± 9.4 kg/m(2)) with 49 ± 5% body fat. At wk 30, more than one third of initial body weight was lost (-38 ± 9%) and consisted of 17 ± 8% from FFM and 83 ± 8% from fat. RMR declined out of proportion to the decrease in body mass, demonstrating a substantial metabolic adaptation (-244 ± 231 and -504 ± 171 kcal/d at wk 6 and 30, respectively, P < 0.01). Energy expenditure attributed to physical activity increased by 10.2 ± 5.1 kcal/kg.d at wk 6 and 6.0 ± 4.1 kcal/kg.d at wk 30 (P < 0.001 vs. zero). CONCLUSIONS Despite relative preservation of FFM, exercise did not prevent dramatic slowing of resting metabolism out of proportion to weight loss. This metabolic adaptation may persist during weight maintenance and predispose to weight regain unless high levels of physical activity or caloric restriction are maintained.

Validity of the Remote Food Photography Method (RFPM) for estimating energy and nutrient intake in near real-time.

Two studies are reported; a pilot study to demonstrate feasibility followed by a larger validity study. Study 1s objective was to test the effect of two ecological momentary assessment (EMA) approaches that varied in intensity on the validity/accuracy of estimating energy intake (EI) with the Remote Food Photography Method (RFPM) over 6 days in free‐living conditions. When using the RFPM, Smartphones are used to capture images of food selection and plate waste and to send the images to a server for food intake estimation. Consistent with EMA, prompts are sent to the Smartphones reminding participants to capture food images. During Study 1, EI estimated with the RFPM and the gold standard, doubly labeled water (DLW), were compared. Participants were assigned to receive Standard EMA Prompts (n = 24) or Customized Prompts (n = 16) (the latter received more reminders delivered at personalized meal times). The RFPM differed significantly from DLW at estimating EI when Standard (mean ± s.d. = −895 ± 770 kcal/day, P < 0.0001), but not Customized Prompts (−270 ± 748 kcal/day, P = 0.22) were used. Error (EI from the RFPM minus that from DLW) was significantly smaller with Customized vs. Standard Prompts. The objectives of Study 2 included testing the RFPMs ability to accurately estimate EI in free‐living adults (N = 50) over 6 days, and energy and nutrient intake in laboratory‐based meals. The RFPM did not differ significantly from DLW at estimating free‐living EI (−152 ± 694 kcal/day, P = 0.16). During laboratory‐based meals, estimating energy and macronutrient intake with the RFPM did not differ significantly compared to directly weighed intake.

Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial

The purpose of this work was to determine the effects of varying levels of dietary protein on body composition and muscle protein synthesis during energy deficit (ED). A randomized controlled trial of 39 adults assigned the subjects diets providing protein at 0.8 (recommended dietary allowance; RDA), 1.6 (2X‐RDA), and 2.4 (3X‐RDA) g kg–1 d–1 for 31 d. A 10‐d weight‐maintenance (WM) period was followed by a 21 d, 40% ED. Body composition and postabsorptive and postprandial muscle protein synthesis were assessed during WM (d 9‐10) and ED (d 30‐31). Volunteers lost (P<0.05) 3.2 ± 0.2 kg body weight during ED regardless of dietary protein. The proportion of weight loss due to reductions in fat‐free mass was lower (P<0.05) and the loss of fat mass was higher (P<0.05) in those receiving 2X‐RDA and 3X‐RDA compared to RDA. The anabolic muscle response to a protein‐rich meal during ED was not different (P>0.05) from WM for 2X‐RDA and 3X‐RDA, but was lower during ED than WM for those consuming RDA levels of protein (energy × protein interaction, P<0.05). To assess muscle protein metabolic responses to varied protein intakes during ED, RDA served as the study control. In summary, we determined that consuming dietary protein at levels exceeding the RDA may protect fat‐free mass during short‐term weight loss.—Pasiakos, S. M., Cao, J. J., Margolis, L. M., Sauter, E. R., Whigham, L. D., McClung, J. P., Rood, J. C., Carbone, J. W., Combs, G. F., Jr., Young, A. J. Effects of high‐protein diets on fat‐free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 27, 3837–3847 (2013). www.fasebj.org

Effect of a controlled high-fat versus low-fat diet on insulin sensitivity and leptin levels in African-American and Caucasian women

African-American women have been shown to be more insulin-resistant than age- and weight-matched Caucasian women, but the reasons for this difference are unclear. The purpose of the present study was to determine whether experimental manipulation of dietary fat intake has differential effects by race on insulin sensitivity (S(I)) in 20 African-American and 11 Caucasian women. Additionally, leptin levels before and after 3 weeks of an isocaloric high-fat ([HF] 50% fat, 35% carbohydrate, and 15% protein) or low-fat ([LF] 20% fat, 55% carbohydrate, and 15% protein) diet were compared. African-American and Caucasian women did not differ significantly in the body mass index (BMI) or percentage body fat at baseline. S(I) (adjusted for BMI) decreased on the HF diet and increased on the LF diet in both races combined relative to the baseline control (control, 2.42 +/- 0.22; HF, 2.29 +/- 0.22; LF, 2.75 +/- 0.21 x 10(-4) min(-1)/microU x mL; main effect of diet, P = .04). There was a 6% decrease in S(I) on the HF diet compared with the control in women of both races, while the LF diet increased S(I) by 6% in African-American and 20% in Caucasian women. Leptin levels increased by 14% on the HF versus control diet in African-Americans (35.2 +/- 3.0 v 30.8 +/- 3.0 ng/mL, P < .01), but did not change with diet in Caucasian women. Glucose and insulin administration had no effect on leptin levels. We conclude that a HF diet consumed over several weeks reduces S(I) in healthy women of both races; however, the magnitude of increase in S(I) on a LF diet is greater in Caucasian women. The HF diet significantly increased leptin levels in African-American women, although there were no other influences of diet, insulin, or race on serum leptin.

Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis

BACKGROUND The effects of essential amino acid (EAA) supplementation during moderate steady state (ie, endurance) exercise on postexercise skeletal muscle metabolism are not well described, and the potential role of supplemental leucine on muscle protein synthesis (MPS) and associated molecular responses remains to be elucidated. OBJECTIVE This randomized crossover study examined whether EAA supplementation with 2 different concentrations of leucine affected post-steady state exercise MPS, whole-body protein turnover, and mammalian target of rapamycin 1 (mTORC1) intracellular signaling. DESIGN Eight adults completed 2 separate bouts of cycle ergometry [60 min, 60% VO(2)peak (peak oxygen uptake)]. Isonitrogenous (10 g EAA) drinks with different leucine contents [leucine-enriched (l)-EAA, 3.5 g leucine; EAA, 1.87 g leucine] were consumed during exercise. MPS and whole-body protein turnover were determined by using primed continuous infusions of [(2)H(5)]phenylalanine and [1-(13)C]leucine. Multiplex and immunoblot analyses were used to quantify mTORC1 signaling. RESULTS MPS was 33% greater (P < 0.05) after consumption of L-EAA (0.08 ± 0.01%/h) than after consumption of EAA (0.06 ± 0.01%/h). Whole-body protein breakdown and synthesis were lower (P < 0.05) and oxidation was greater (P < 0.05) after consumption of L-EAA than after consumption of EAA. Regardless of dietary treatment, multiplex analysis indicated that Akt and mammalian target of rapamycin phosphorylation were increased (P < 0.05) 30 min after exercise. Immunoblot analysis indicated that phosphorylation of ribosomal protein S6 and extracellular-signal regulated protein kinase increased (P < 0.05) and phosphorylation of eukaryotic elongation factor 2 decreased (P < 0.05) after exercise but was not affected by dietary treatment. CONCLUSION These findings suggest that increasing the concentration of leucine in an EAA supplement consumed during steady state exercise elicits a greater MPS response during recovery. This trial is registered at clinicaltrials.gov as NCT01366924.

Calorie Restriction and Bone Health in Young, Overweight Individuals

BACKGROUND Calorie restriction (CR) is promoted to increase longevity, yet this regimen could lead to bone loss and fracture and therefore affect quality of life. METHODS Forty-six individuals were randomized to 4 groups for 6 months: (1) healthy diet (control group); (2) 25% CR from baseline energy requirements (CR group); (3) 25% energy deficit by a combination of CR and increased aerobic exercise (CR + EX group); and (4) low-calorie diet (890 kcal/d; goal, 15% weight loss) followed by weight maintenance (LCD group). Bone mineral density (total body and hip by dual-energy x-ray absorptiometry) and serum bone markers (bone-specific alkaline phosphatase, osteocalcin, cross-linked C-telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured at baseline and after 6 months. RESULTS Mean +/- SE body weight was reduced by -1.0% +/- 1.1% (control), -10.4% +/- 0.9% (CR), -10.0% +/- 0.8% (CR + EX), and -13.9% +/- 0.7% (LCD). Compared with the control group, none of the groups showed any change in bone mineral density for total body or hip. Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups, with the largest change observed in the LCD group (CR, 23% +/- 10%; CR + EX, 22% +/- 9%; and LCD, 74% +/- 16% vs control, 4% +/- 10%). Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group. With regard to bone formation, bone alkaline phosphatase levels were decreased in the CR group (-23% +/- 10%) but were unchanged in the CR + EX, LCD, and control groups. CONCLUSIONS Moderate CR, with or without exercise, that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults. Longer studies with assessments of bone architecture are needed to confirm that CR nutrient-dense diets have no deleterious effect on bone health. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00099151.