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At least 415 records · Page 23
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Exercise alters molecular profiles of inflammation and substrate metabolism in human white adipose tissue

White adipose tissue (WAT) plays a significant role in whole body energy homeostasis, and its excess typifies obesity. In addition to WAT quantity, perturbations in the basic cellular processes of WAT (i.e., quality) are also associated with obesity and metabolic disease. Exercise training alleviates metabolic perturbations associated with obesity; however, the underlying molecular mechanisms that drive these metabolic adaptations in WAT are not well described. For this work, abdominal subcutaneous WAT biopsies were collected after an acute bout of exercise (1 day after) at baseline and following 3 wk of supervised aerobic training in sedentary overweight women (n = 6) without alterations in body weight and fat mass. RNA-seq, global proteomics, and phosphoproteomics in WAT revealed training-induced changes in 1,527 transcripts, 154 proteins, and 144 phosphosites, respectively. Training decreased abundance of transcripts and proteins involved in inflammation and components of the extracellular matrix and increased abundance of transcripts and proteins related to fatty acid esterification and lipolysis. In summary, short-term aerobic training significantly reduces local inflammation and increases lipid metabolism in WAT of sedentary overweight women—independent of alterations in body and fat mass. As such, some of the health benefits of aerobic training may occur through molecular alterations in WAT (i.e., enhanced quality) rather than a sheer reduction in WAT quantity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

An Evaluation of Army Wellness Center Clients’ Health-Related Outcomes

Purpose: To examine whether Army community members participating in a best-practice based workplace health promotion program (WHPP) experience goal-moderated improvements in health-related outcomes. Design: Pretest/posttest outcome evaluation examining an autonomously participating client cohort over 1 year. Setting: Army Wellness Center facilities on 19 Army installations. Participants: Army community members sample (N = 5703), mostly Active Duty Soldiers (64%). Intervention: Assessment of health risks with feedback, health assessments, health education classes, and health coaching sessions conducted by health educators at a recommended frequency of once a month for 3 to 12 months. Measures: Initial and follow-up outcome assessments of body mass index (BMI), body fat, cardiorespiratory fitness, blood pressure, and perceived stress. Analysis: Mixed model linear regression testing for goal-moderated improvements in outcomes. Results: Clients experienced significant improvements in body fat (−2% change), perceived stress (−6% to −12% change), cardiorespiratory fitness (+6% change), and blood pressure (−1% change) regardless of health-related goal. Only clients with a weight loss goal experienced BMI improvement (−1% change). Follow-up outcome assessment rates ranged from 44% (N = 2509) for BMI to 6% (N = 342) for perceived stress. Conclusion: Army Wellness Center clients with at least 1 follow-up outcome assessment experienced improvements in military readiness correlates and chronic disease risk factors. Evaluation design and follow-up-related limitations notwithstanding results suggest that best practices in WHPPs can effectively serve a globally distributed military force.

Rivera, L. Omar↗
DOE OSTI2018

Copper-dependent amino oxidase 3 governs selection of metabolic fuels in adipocytes

Copper (Cu) has emerged as an important modifier of body lipid metabolism. However, how Cu contributes to the physiology of fat cells remains largely unknown. We found that adipocytes require Cu to establish a balance between main metabolic fuels. Differentiating adipocytes increase their Cu uptake along with the ATP7A-dependent transport of Cu into the secretory pathway to activate a highly up-regulated amino-oxidase copper-containing 3 (AOC3)/semicarbazide-sensitive amine oxidase (SSAO); in vivo, the activity of SSAO depends on the organism's Cu status. Activated SSAO oppositely regulates uptake of glucose and long-chain fatty acids and remodels the cellular proteome to coordinate changes in fuel availability and related downstream processes, such as glycolysis, de novo lipogenesis, and sphingomyelin/ceramide synthesis. The loss of SSAO-dependent regulation due to Cu deficiency, limited Cu transport to the secretory pathway, or SSAO inactivation shifts metabolism towards lipid-dependent pathways and results in adipocyte hypertrophy and fat accumulation. The results establish a role for Cu homeostasis in adipocyte metabolism and identify SSAO as a regulator of energy utilization processes in adipocytes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2011

Reduction in Inflammatory Gene Expression in Skeletal Muscle from Roux-en-Y Gastric Bypass Patients Randomized to Omentectomy

To examine the effects of Roux-en-Y gastric bypass (RYGB) surgery with and without laparoscopic removal of omental fat (omentectomy) on the temporal gene expression profiles of skeletal muscle. Previously reported were the whole-body metabolic effects of a randomized, single-blinded study in patients receiving RYGB surgery stratified to receive or not receive omentectomy. In this follow up study we report on changes in skeletal muscle gene expression in a subset of 21 patients, for whom biopsies were collected preoperatively and at either 6 months or 12 months postoperatively. RNA isolated from skeletal muscle biopsies of 21 subjects (8 without omentectomy and 13 with omentectomy) taken before RYGB or at 6 and 12 months postoperatively were subjected to gene expression profiling via Exon 1.0 S/T Array and Taqman Low Density Array. Robust Multichip Analysis and gene enrichment data analysis revealed 84 genes with at least a 4-fold expression difference after surgery. At 6 and 12 months the RYGB with omentectomy group displayed a greater reduction in the expression of genes associated with skeletal muscle inflammation (ANKRD1, CDR1, CH25H, CXCL2, CX3CR1, IL8, LBP, NFIL3, SELE, SOCS3, TNFAIP3, and ZFP36) relative to the RYGB nonomentectomy group. Expressions of IL6 and CCL2 were decreased at all postoperative time points. There was differential expression of genes driving protein turnover (IGFN1, FBXW10) in both groups over time and increased expression of PAAF1 in the non-omentectomy group at 12 months. Evidence for the activation of skeletal muscle satellite cells was inferred from the up-regulation of HOXC10. The elevated post-operative expression of 22 small nucleolar RNAs and the decreased expression of the transcription factors JUNB, FOS, FOSB, ATF3 MYC, EGR1 as well as the orphan nuclear receptors NR4A1, NR4A2, NR4A3 suggest dramatic reorganizations at both the cellular and genetic levels. These data indicate that RYGB reduces skeletal muscle inflammation, and removal of omental fat further amplifies this response.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Dual Function of Novel Pollen Coat (Surface) Proteins: IgE-binding Capacity and Proteolytic Activity Disrupting the Airway Epithelial Barrier

The pollen coat is the first structure of the pollen to encounter the mucosal immune system upon inhalation. Prior characterizations of pollen allergens have focused on water-soluble, cytoplasmic proteins, but have overlooked much of the extracellular pollen coat. Due to washing with organic solvents when prepared, these pollen coat proteins are typically absent from commercial standardized allergenic extracts (i.e., ‘‘de-fatted’’), and, as a result, their involvement in allergy has not been explored. Using a unique approach to search for pollen allergenic proteins residing in the pollen coat, we employed transmission electron microscopy (TEM) to assess the impact of organic solvents on the structural integrity of the pollen coat. TEM results indicated that de-fatting of Cynodon dactylon (Bermuda grass) pollen (BGP) by use of organic solvents altered the structural integrity of the pollen coat. The novel IgE-binding proteins of the BGP coat include a cysteine protease (CP) and endoxylanase (EXY). The full-length cDNA that encodes the novel IgE-reactive CP was cloned from floral RNA. The EXY and CP were purified to homogeneity and tested for IgE reactivity. The CP from the BGP coat increased the permeability of human airway epithelial cells, caused a clear concentration-dependent detachment of cells, and damaged their barrier integrity. Using an immunoproteomics approach, novel allergenic proteins of the BGP coat were identified. These proteins represent a class of novel dual-function proteins residing on the coat of the pollen grain that have IgE-binding capacity and proteolytic activity, which disrupts the integrity of the airway epithelial barrier. The identification of pollen coat allergens might explain the IgE-negative response to available skin-prick-testing proteins in patients who have positive symptoms. Further study of the role of these pollen coat proteins in allergic responses is warranted and could potentially lead to the development of improved diagnostic and therapeutic tools.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease

In the United States non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting an estimated 80 to 100 million people. It occurs in every age group, but predominantly in people with risk factors such as obesity and type 2 diabetes. NAFLD is marked by fat accumulation in the liver leading to liver inflammation, which may lead to scarring and irreversible damage progressing to cirrhosis and liver failure. In animal models, genetic ablation of the protein G0S2 leads to alleviation of liver damage and insulin resistance in high fat diets. The research presented in this paper aims to aid in rational based drug design for the treatment of NAFLD by providing a pathway for a solution state NMR structure of G0S2. Here we describe the expression of G0S2 in an E. coli system from two different constructs, both of which are confirmed to be functionally active based on the ability to inhibit the activity of Adipose Triglyceride Lipase. In one of the constructs, preliminary NMR spectroscopy measurements show dominant alpha-helical characteristics as well as resonance assignments on the N-terminus of G0S2, allowing for further NMR work with this protein. Additionally, the characterization of G0S2 oligomers are outlined for both constructs, suggesting that G0S2 may defensively exist in a multimeric state to protect and potentially stabilize the small 104 amino acid protein within the cell. This information presented on the structure of G0S2 will further guide future development in the therapy for NAFLD.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

How did the world’s first atomic bomb get its name? Looking back on the Trinity test on its 76th anniversary

The world’s first-ever atomic bomb is called The Gadget. It was detonated in the New Mexico desert on July 16,1945 during the Trinity test, verifying that an implosion-type plutonium bomb would be successful when released above Nagasaki just weeks later. That atomic bomb was called Fat Man and it was a weaponized version of the Trinity device of The Gadget. According to the longtime lore, the bulbous-looking Fat Man bomb’s name was inspired by British Prime Minister Winston Churchill. After the Thin Man bomb, whose moniker was inspired by the U.S. President Franklin Roosevelt, didn’t come to fruition, the gun-type uranium atomic bomb named Little Boy was developed. It was likely dubbed as such because it was smaller in size.

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF↗
DOE OSTI2024

Diabetes-specific formula with standard of care improves glycemic control, body composition, and cardiometabolic risk factors in overweight and obese adults with type 2 diabetes: results from a randomized controlled trial

Background and aims Medical nutrition therapy is important for diabetes management. This randomized controlled trial investigated the effects of a diabetes-specific formula (DSF) on glycemic control and cardiometabolic risk factors in adults with type 2 diabetes (T2D). Methods Participants ( n = 235) were randomized to either DSF with standard of care (SOC) (DSF group; n = 117) or SOC only (control group; n = 118). The DSF group consumed one or two DSF servings daily as meal replacement or partial meal replacement. The assessments were done at baseline, on day 45, and on day 90. Results There were significant reductions in glycated hemoglobin (−0.44% vs. –0.26%, p = 0.015, at day 45; −0.50% vs. −0.21%, p = 0.002, at day 90) and fasting blood glucose (−0.14 mmol/L vs. +0.32 mmol/L, p = 0.036, at day 90), as well as twofold greater weight loss (−1.30 kg vs. –0.61 kg, p < 0.001, at day 45; −1.74 kg vs. –0.76 kg, p < 0.001, at day 90) in the DSF group compared with the control group. The decrease in percent body fat and increase in percent fat-free mass at day 90 in the DSF group were almost twice that of the control group (1.44% vs. 0.79%, p = 0.047). In addition, the percent change in visceral adipose tissue at day 90 in the DSF group was several-fold lower than in the control group (−6.52% vs. –0.95%, p < 0.001). The DSF group also showed smaller waist and hip circumferences, and lower diastolic blood pressure than the control group (all overall p ≤ 0.045). Conclusion DSF with SOC yielded significantly greater improvements than only SOC in glycemic control, body composition, and cardiometabolic risk factors in adults with T2D.

Tey, Siew Ling↗
DOE OSTI2022

The Supplementation of FloraMax-B11 Did Not Affect the Bile Acid Neosynthesis and the Enterohepatic Circulation in Broiler Chickens

Most probiotics possess bile salt hydrolase enzymes and may increase bile acid excretion and negatively affect fat digestion and absorption. Therefore, the study objective was to determine the time course effects of a commercial probiotic (P) FloraMax-B11 (FM) supplementation on bile acid neosynthesis and enterohepatic circulation in broiler chickens. Fertile Ross 708 eggs were incubated under standard commercial conditions. At hatch, chicks (n = 550) were randomly assigned to 5 treatment groups (n = 5 replicates per treatment group) with 22 birds per pen. The 5 treatment groups consisted of: control group (C, normal water from hatch to 35 days of age without supplements); P3, water supplemented with FM for the first 3 days post-hatch followed by normal water until day 35; P10, water supplemented with FM for the first 10 days post-hatch followed by normal water until day 35; P35, water supplemented with FM from hatch to day 35; and AGP, water supplemented with antibiotic growth promoter (AGP) from hatch until day 35. Ileum, liver, and plasma were collected at hatch, days 3, 10, 21, and 35 post-hatch. The relative mRNA expression of genes involved in bile acid synthesis (CYP7A1, CYP8B1, FXR, FGFR4, and FGF19) and transport (ASBT, I-BABP, OSTα, OSTβ, and BSEP) as well as ileal deoxycholic acid and plasma cholic acid were determined. There was no FM and AGP interaction for any of the response criteria. No FM or AGP effects were observed (p > 0.05) for any genes, except FGF19, which expression was increased (p < 0.0001) in AGP compared to P35. No FM or AGP effects were observed (p > 0.05) for levels of deoxycholic and cholic acids. However, all the genes, deoxycholic acid, and plasma cholic acid were affected by age (p < 0.0001). In general, the data indicate that FM did not negatively impact bile acid metabolism and enterohepatic circulation, which appeared to be age dependent. However, more research should be conducted to confirm these results and investigate the effects of FM on bile acid metabolism, fat digestion, and intestinal microbiota in broiler chickens.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1973

Advanced investigation of two-phase charge-coupled devices

The performance of experimental two phase, charge-coupled shift registers constructed using polysilicon gates overlapped by aluminum gates was studied. Shift registers with 64, 128, and 500 stages were built and operated. Devices were operated at the maximum clock frequency of 20 MHz. Loss per transfer of less than .0001 was demonstrated for fat zero operation. The effect upon transfer efficiency of various structural and materials parameters was investigated including substrate orientation, resistivity, and conductivity type; channel width and channel length; and method of channel confinement. Operation of the devices with and without fat zero was studied as well as operation in the complete charge transfer mode and the bias charge, or bucket brigade mode.

Kosonocky, W. F.↗
NASA NTRS1973

Effects of gravity on ontogeny in animals.

Inversion or clinostat rotation of frogs' eggs demonstrated a critical period of enhanced gravity-sensitivity prior to the first cleavage. These results were corroborated by centrifugation studies which localized the period of maximal sensitivity at approximately 20 minutes post-fertilization. Eggs of various invertebrates suspended in aqueous solution proved capable of normal development following brief ultracentrifugation. Among fly larvae, grasshopper nymphs, turtles, mice, rats, and chickens, growth rates were inversely related to G-force, and maximal chronic acceleration tolerated was inversely related to body size. Body composition data demonstrated the importance of separately evaluating fat and the fat-free portion of the body in studies of the effect of acceleration on growth in homeotherms. The attempt to evaluate the effect of weightlessness on the development of frogs' eggs in Biosatellite 2 was inconclusive for technical reasons.

Pitts, G. C.↗
NASA NTRS1976

Body composition changes in men and women after 2-3 weeks of bed rest

Several parameters of body composition were measured in eight men before and after 14 days of continuous recumbency, and in eight women before and after 17 days of recumbency. The parameters measured included body weight, body water, body potassium, plasma volume, and plasma protein concentrations. From these, values were derived for body fat content, lean body mass, body mass, and circulating plasma proteins. In general, the men and women responded similarly to continuous recumbency. Characteristically, there was significant reduction of plasma volume and body potassium in both groups. The women showed a significant reduction in circulating plasma protein, entirely in the albumin fraction; a similar change was observed in the men. The women, but not the men, showed a significant increase in circulating fibrinogen. Both men and women lost body cell mass, while body fat content remained the same or tended to increase slightly. It is expected that similar changes would occur in weightlessness. It is further concluded that women should tolerate the weightlessness of space flight physiologically as well as men.

Pace, N.↗
NASA NTRS1978

Rat growth during chronic centrifugation

Female weanling rats were chronically centrifuged at 4.15 G with controls at terrestrial gravity. Samples were sacrificed for body composition studies at 0, 28, 63, 105 and 308 days of centrifugation. The centrifuged group approached a significantly lower mature body mass than the controls (251 and 318g) but the rate of approach was the same in both groups. Retirement to 1G on the 60th day resulted in complete recovery. Among individual components muscle, bone, skin, CNS, heart, kidneys, body water and body fat were changed in the centrifuged group. However, an analysis of the growth of individual components relative to growth of the total fat-free compartment revealed that only skin (which increased in mass) was responding to centrifugation per se.

Pitts, G. C.↗
NASA NTRS1978

Controlled cellular energy conversion in brown adipose tissue thermogenesis

Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

Horowitz, J. M.↗
NASA NTRS1981

Simulated spaceflight effects on mating and pregnancy of rats

The mating of rats was studied to determine the effects of: simulated reentry stresses at known stages of pregnancy, and full flight simulation, consisting of sequential launch stresses, group housing, mating opportunity, diet, simulated reentry, and postreentry isolation of male and female rats. Uterine contents, adrenal mass and abdominal fat as a proportion of body mass, duration of pregnancy, and number and sex of offspring were studied. It is found that: (1) parturition following full flight simulation was delayed relative to that of controls; (2) litter size was reduced and resorptions increased compared with previous matings in the same group of animals; and (3) abdominal fat was highly elevated in animals that were fed the Soviet paste diet. It is suggested that the combined effects of diet, stress, spacecraft environment, and weightlessness decreased the probability of mating or of viable pregnancies in the Cosmos 1129 flight and control animals.

Sabelman, E. E.↗
NASA NTRS1982

Response of rat body composition to simultaneous exercise and centrifugation at 3.14g

A study is described calling into question the hypothesis that an increased physical load during chronic centrifugation contributes to the body composition changes observed in centrifuged rats. Considering fat-free and fat-free dry masses of the total body and carcass, it is seen that centrifugation combined with either wheel running or restraint reduced these masses to approximately 85% of the respective 1-g values, that is, the same result with either sedentary rats or rats running several hundred meters per day. It is pointed out that if an effect of a centrifugation-induced load is present but hidden by opposing factors, an analysis of variance should reveal it as an interaction between acceleration and other variables; however, no such interactions are found here. Tables are included emphasizing the pervasive influence of chronic centrifugation after only 12 days exposure.

Pitts, G. C.↗
NASA NTRS1982

Skeletal abnormalities in rats induced by simulated weightlessness

A hypokinetic model has been developed which attempts to simulate the weightlessness experienced during space flight. Male rats were suspended from the model with a head-down tilt for a two-week period. Total mechanical unloading of the hind limbs and partial unloading of the fore limbs occurred. In comparison to pair-fed control rats, the skeletal alterations in the proximal tibial and humeral metaphyses of suspended rats were determined to be a diminished rate of longitudinal bone growth, a reduced mass of mineralized tissue, and an accumulation of marrow fat. Also, suspended rats exhibited decreased numbers of osteoblasts and increased numbers of osteoclasts immediately adjacent to the growth plate-metaphyseal junction at both skeletal sites. Although the reduction in mineralized tissue and the fat accumulation were more marked in the tibia, the skeletal changes in the proximal tibial and humeral metaphyses were generally comparable. The observed abnormalities may be due to mechanical unloading and/or a hypersecretion of corticosteroids.

Wronski, T. J.↗
NASA NTRS1983

Quantitation of tissue loss during prolonged space flight

An analysis of data from the three Skylab missions was performed to assess the lean body mass (LBM) and fat components of inflight body weight loss. Six methods for determining LBM were employed based on changes in total body water, total body potassium, nitrogen balance, potassium balance, and stereophotometric-body density. Those based solely on body potassium, and potassium and nitrogen balances (when expressed as shifts from preflight control), consistently overestimated LBM loss unless appropriate corrections were made. The average results from the various methods indicated that of a mean inflight total body weight loss of 2.7 + or - 0.3 kg (SD) for all nine crewmembers, more than half (1.5 + or - 0.3 kg) can be attributed to loss of LBM (including 1.1 kg body water), the remainder (1.2 + or - 0.3 kg) being derived from fat stores. The reduction of LBM appeared to be complete after the first month of flight and thereafter was largely independent of mission duration, diet, and exercise.

Leonard, J. I.↗