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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Circulating unmethylated CHTOP and INS DNA fragments provide evidence of possible islet cell death in youth with obesity and diabetes

Circulating unmethylated DNA fragments arising from the human INS gene have been proposed as biomarkers of islet beta-cell death and diabetes risk, but this gene alone does not yield sufficiently specific information to report ß-cell death. We employed an unbiased approach to identify the CHTOP gene as a new candidate biomarker whose CpGs show a greater frequency of unmethylation in human islets. Although both INS and CHTOP contained unmethylated CpG sites in several human tissues, they occurred in a non-overlapping pattern. Based on Naïve Bayes classifier analysis, the two genes used together, however, report 100% specificity for islet damage. Compared to healthy controls, differentially methylated CHTOP and INS levels were higher in youth with new onset type 1 diabetes (T1D) and, unexpectedly, in healthy autoantibody-negative youth who have first-degree relatives with T1D. When tested in youth at risk for type 2 diabetes (T2D), increased levels of unmethylated INS and CHTOP were observed in obese individuals. Our data suggest that concurrent measurement of circulating unmethylated INS and CHTOP detects islet death in youth at risk for both T1D and T2D, and support the use of multiple parameters to increase the confidence of detecting islet damage in at-risk individuals.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2001

A new perspective on adiposity in a naturally obese mammal

Many mammals seasonally reduce body fat due to inherent periods of fasting, which is associated with decreased leptin concentrations. However, no data exist on the correlation between fat mass (FM) and circulating leptin in marine mammals, which have evolved large fat stores as part of their adaptation to periods of prolonged fasting. Therefore, FM was estimated (by tritiated water dilution), and serum leptin and cortisol were measured in 40 northern elephant seal (Mirounga angustirostris) pups early (<1 wk postweaning) and late (6-8 wk postweaning) during their natural, postweaning fast. Body mass (BM) and FM were reduced late; however, percent FM (early: 43.9 +/- 0.5, late: 45.5 +/- 0.5%) and leptin [early: 2.9 +/- 0.1 ng/ml human equivalents (HE), late: 3.0 +/- 0.1 ng/ml HE] did not change. Cortisol increased between early (9.2 +/- 0.5 microg/dl) and late (16.3 +/- 0.9 microg/dl) periods and was significantly and negatively correlated with BM (r = 0.426; P < 0.0001) and FM (r = 0.328; P = 0.003). FM and percent FM were not correlated (P > 0.10) with leptin at either period. The present study suggests that these naturally obese mammals appear to possess a novel cascade for regulating body fat that includes cortisol. The lack of a correlation between leptin and FM may reflect the different functions of fat between terrestrial and marine mammals.

Non-NASA Center↗
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↗
NASA NTRS1977

Exercise, dietary obesity, and growth in the rat

Experiments were conducted on weanling male rats 35 days old and weighing about 100 g to determine how endurance-type exercise and high-fat diet administered during growth influence body mass and composition. The animals were divided into four weight-matched groups of 25 animals each: group I - high-fat diet, exercised; group II - chow, exercised; group III - high-fat diet, sedentary; and group IV - chow, sedentary. During growth, masses of water, muscle and skin increased as functions of body size; bone as a function of age; and heart, liver, gut, testes, and CNS were affected by combinations of size, age, activity, and diet. Major conclusions are that growth in body size is expressed more precisely with fat-free body mass (FFBM), that late rectilinear growth is probably attributable to fat accretion, and that the observed influences on FFBM of exercise and high-fat diet are obtained only if the regimen is started at or before age 5-7 weeks.

Pitts, G. C.↗
NASA NTRS2003

Evolutionary, structural and biochemical evidence for a new interaction site of the leptin obesity protein

The Leptin protein is central to the regulation of energy metabolism in mammals. By integrating evolutionary, structural, and biochemical information, a surface segment, outside of its known receptor contacts, is predicted as a second interaction site that may help to further define its roles in energy balance and its functional differences between humans and other mammals.

Evolution, Molecular↗
NASA NTRS2015

NASA Child Fitness Promotion Program in Young Children in South Korea

Childhood obesity is a serious global public health concern (WHO, 2015; Wang Y & Lobstein T, 2006). Low self-esteem and related mental health problems are common in obese children (Strauss RS, 2000) as well as poor academic performance and career development (Gurley-Calvez T, 2010).Westernized dietary habits and sedentary lifestyles are identified as the major risk factors of current alarming rate of obesity along with genetic susceptibility (Popkin BM, 1999). Children in many countries, including South Korea, have become increasingly sedentary due to urbanization changes in their respective societies (Ng SW, et al. 2009, Salmon J et al. 2011). In particular, South Korea had abundant dissemination of mobile technology, such as tablet and smart phone devices. Children have become reliant on mobile devices and are less likely to perform physical activities (Do, et al, 2013). Effective and sustainable intervention programs are needed to fight the global obesity epidemic (IOM, 2012; Wang Y et al, 2013; Wang Y et al, 2015). Previous studies suggested focus on prevention strategies that begin in early childhood, a period when children establish their life habits. (Salmon J et al. 2011). Recent systematic reviews and meta-analysis including ours found that obesity prevention programs for young children have a greater intervention effect (Waters E, et al, 2011; Wang Y et al, 2013; Wang Y et al, 2015). The NASA Mission X: Train Like an Astronaut (MX) program was developed to promote children's exercise and healthy eating with excitement for training like an astronaut (Lloyd C, 2012).At present, the NASA MX Program covered 28 countries, enrolled children through their teachers in school setting (MX report 2014, 2015). This pilot study adapted the NASA MX intervention program for young children in South Korea. We assessed its feasibility and effectiveness in promoting physical activity (PA) in children and in improving parents' perspectives. We also examined the status of PA in young children. More than 80% of five-year-old children go to a Kindergarten or day care center in South Korea (MH Suh et al, 2013).Thus, reaching young children through child care and education settings could be a good approach for early childhood obesity prevention.

Min, Jungwon↗
DOE OSTI2020

Estimation of Body Fat Percentage for Clinical Pharmacokinetic Studies in Children

Obesity is a prevalent childhood condition and the degree of adiposity appears likely to be an important covariate in the pharmacokinetics (PKs) of many drugs. We undertook these studies to facilitate the evaluation and, where appropriate, quantification of the covariate effect of body fat percentage (BF%) on PK parameters in children. We examined two large databases to determine the values and variabilities of BF% in children with healthy body weights and in those with obesity, comparing the accuracy and precision of BF% estimation by both clinical methods and demographically derived techniques. Additionally, we conducted simulation studies to evaluate the utility of the several methods for application in clinical trials. BF% was correlated with body mass index (BMI), but was highly variable among both children with healthy body weights and those with obesity. Bio‐impedance and several demographically derived techniques produced mean estimates of BF% that differed from dual x‐ray absorptiometry by < 1% (accuracy) and a SD of 5% or less (precision). Simulation studies confirmed that when the differences in precision among the several methods were small compared with unexplained between‐subject variability of a PK parameter, the techniques were of similar value in assessing the contribution of BF%, if any, as a covariate for that PK parameter. The combination of sex and obesity stage explained 68% of the variance of BF% with BMI. The estimation of BF% from sex and obesity stage can routinely be applied to PK clinical trials to evaluate the contribution of BF% as a potential covariate.

Green, Thomas P.↗
NASA NTRS2015

Effect of the Adapted NASA Mission X International Child Fitness Program on Young Children and their Parents in South Korea

Obesity has become a global epidemic. Childhood obesity is global public health concern including in South Korea where 16.2% of boys and 9.9% of girls are overweight or obese in 2011. Effective and sustainable intervention programs are needed for prevention of childhood obesity. Obesity prevention programs for young children may have a greater intervention effect than in older children. The NASA Mission X: Train Like an Astronaut (MX) program was developed to promote children's exercise and healthy eating by tapping into their excitement for training like an astronaut. This study aimed to examine the feasibility and effectiveness of the adapted NASA MX intervention in promoting PA in young children and in improving parents' related perspectives.

Min, Jungwon↗
DOE OSTI2020

Temporospatial shifts in the human gut microbiome and metabolome after gastric bypass surgery

Although the etiology of obesity is not well-understood, genetic, environmental, and microbiome elements are recognized as contributors to this rising pandemic. For morbid obesity, Roux-en-Y gastric bypass (RYGB) surgery alters the fecal microbiome, but data are sparse on temporal and spatial changes in the microbiome and metabolome. We characterized the structure and metabolism of the microbial communities in the gut lumen and on mucosal surfaces in morbidly obese individuals before and after RYGB surgery, and we compared our longitudinal cohort to a previously studied cross-sectional one. RYGB concurrently changed the gut microbiome and led to improvements of obesity comorbidities. Changes in the gut microbiome were reflected in the metabolome, including fermentation products and bile acids. The effects persisted 12 months post-surgery, and the microbiomes and metabolomes were similar to those found for the cross-sectional RYGB cohort. Thus, RYGB surgery had profound and persistent impacts on the intestinal microbiome and metabolome.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

High-fat and high-carbohydrate diets increase bone fragility through TGF-β–dependent control of osteocyte function

Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood. Using male mouse models of obesity, we discovered TGF-β signaling plays a critical role in mediating the effects of obesity on bone. High-carbohydrate and high-fat diets increase TGF-β signaling in osteocytes, which impairs their mitochondrial function, increases cellular senescence, and compromises perilacunar/canalicular remodeling and bone quality. By specifically inhibiting TGF-β signaling in mouse osteocytes, some of the negative effects of high-fat and high-carbohydrate diets on bones, including the lacunocanalicular network, perilacunar/canalicular remodeling, senescence, and mechanical properties such as yield stress, were mitigated. DMP1-Cre–mediated deletion of TGF-β receptor II also blunted adverse effects of high-fat and high-carbohydrate diets on energy balance and metabolism. These findings suggest osteocytes are key in controlling bone quality in response to high-fat and high-carbohydrate diets. Calibrating osteocyte function could mitigate bone fragility associated with metabolic diseases while reestablishing energy balance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Hepatic SerpinA1 improves energy and glucose metabolism through regulation of preadipocyte proliferation and UCP1 expression

Lipodystrophy and obesity are associated with insulin resistance and metabolic syndrome accompanied by fat tissue dysregulation. Here, we show that serine protease inhibitor A1 (SerpinA1) expression in the liver is increased during recovery from lipodystrophy caused by the adipocyte-specific loss of insulin signaling in mice. SerpinA1 induces the proliferation of white and brown preadipocytes and increases the expression of uncoupling protein 1 (UCP1) to promote mitochondrial activation in mature white and brown adipocytes. Liver-specific SerpinA1 transgenic mice exhibit increased browning of adipose tissues, leading to increased energy expenditure, reduced adiposity and improved glucose tolerance. Conversely, SerpinA1 knockout mice exhibit decreased adipocyte mitochondrial function, impaired thermogenesis, obesity, and systemic insulin resistance. SerpinA1 forms a complex with the Eph receptor B2 and regulates its downstream signaling in adipocytes. These results demonstrate that SerpinA1 is an important hepatokine that improves obesity, energy expenditure and glucose metabolism by promoting preadipocyte proliferation and activating mitochondrial UCP1 expression in adipocytes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Synchrotron fluorescence imaging of individual mouse beta-cells reveals changes in zinc, calcium, and iron in a model of low-grade inflammation

Pancreatic beta-cells synthesize and secrete insulin maintaining an organism's energy homeostasis. In humans, beta-cell dysfunction and death contribute to the pathogenesis of type 2 diabetes (T2D). Although the causes of beta-cell dysfunction are complex, obesity-induced low-grade systemic inflammation plays a role. For example, obese individuals exhibiting increased levels of proinflammatory cytokines IL-6 and IL-1beta have a higher risk of beta-cell dysfunction and T2D. Interestingly, obesity-induced inflammation changes the expression of several cellular metal regulating genes, prompting this study to examine changes in the beta-cell metallome after exposure to proinflammatory-cytokines. Here, primary mouse beta-cells were exposed to a combination of IL-6 and IL-1beta for 48 hours, were chemically fixed and imaged by synchrotron X-ray fluorescent microscopy. Quantitative analysis showed a surprising 2.4-fold decrease in the mean total cellular content of zinc from 158 ± 57.7 femtograms (fg) to 65.7 ± 29.7 fg; calcium decreased from 216 ± 67.4 to 154.3 ± 68.7 fg (control vs. cytokines, respectively). The mean total cellular iron content slightly increased from 30.4 ± 12.2 to 47.2 ± 36.4 fg after cytokine treatment; a sub-population of cells (38%) exhibited larger increases of iron density. Changes in the subcellular distributions of zinc and calcium were observed after cytokine exposure. Beta-cells contained numerous iron puncta that accumulated still more iron after exposure to cytokines. These findings provide evidence that exposure to low levels of cytokines is sufficient to cause changes in the total cellular content and/or subcellular distribution of several metals known to be critical for normal beta-cell function.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Reexamining Fat: Exploring Diversity, Plasticity, Development, Functional Implication, and Therapeutic Options

Obesity has become so prevalent in many developed countries that it is increasingly perceived as a new norm, despite decades of interventions and drug development. Although research continues to explore novel strategies, no single approach to date has demonstrated sustained success in reducing its population-level dominance. This underscores the need to better evaluate and integrate the growing body of knowledge surrounding obesity’s multifaceted nature. Stamped under one ‘fat’ name, adipose tissue varies by color, location, morphology, composition, and function. This variability suggests a level of complexity that demands deeper investigation. Although the relevance and roles of different adipose types have been extensively discussed throughout the literature, their interdependence, synergy, and collective impact on the body remain to be fully expounded. This review aims to further consolidate and elucidate the available information on the different adipose tissue types and their association with obesity and metabolic health. We also discuss existing and emerging therapeutic strategies, highlighting their respective strengths and limitations.

BAT↗