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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Salivary microbiome composition changes after bariatric surgery

Recent studies show that the salivary microbiome in subjects with obesity differ from those without obesity, but the mechanism of interaction between the salivary microbiome composition and body weight is unclear. Herein we investigate this relation by analyzing saliva samples from 35 adult patients with obesity undergoing bariatric surgery. Our aim was to describe salivary microbiome changes during body weight loss on an individual-specific level, and to elucidate the effect of bariatric surgery on the salivary microbiome which has not been studied before. Analysis of samples collected before and 1 day after surgery, as well as 3 and 12 months after surgery, showed that the salivary microbiome changed in all study participants, but these changes were heterogeneous. In the majority of participants proportions of Gemella species, Granulicatella elegans, Porphyromonas pasteri, Prevotella nanceiensis and Streptococcus oralis decreased, while Veillonella species, Megasphaera micronuciformis and Prevotella saliva increased. Nevertheless, we found participants deviating from this general trend which suggests that a variety of individual-specific factors influence the salivary microbiome composition more effectively than the body weight dynamics alone. The observed microbiome alternations could be related to dietary changes. Therefore, further studies should focus on association with altered taste preferences and potential oral health consequences.

59 BASIC BIOLOGICAL SCIENCES↗
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↗
NASA NTRS2001

Determinants Affecting Physical Activity Levels In Animal Models

Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play all underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multi-factorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked making it difficult to determine whether a single, combination or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to tile ventral medial hypothalamus and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

Tou, Janet C. L.↗
NASA NTRS2002

Determinants affecting physical activity levels in animal models

Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play an underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multifactorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked, making it difficult to determine whether a single, combination, or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to the ventral medial hypothalamus, and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

Review↗
NASA NTRS2000

Dietary fat intake, supplements, and weight loss

Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been tested for their effectiveness or safety over prolonged periods of time.

NASA Discipline Musculoskeletal↗
DOE OSTI2023

Restrictive spirometry pattern among construction trade workers

Spirometry-based studies of occupational lung disease have mostly focused on obstructive or mixed obstructive/restrictive outcomes. We wanted to determine if restrictive spirometry pattern (RSP) is associated with occupation and increased mortality. Study participants included 18,145 workers with demographic and smoking data and repeatable spirometry. The mortality analysis cohort included 15,445 workers with known vital status and cause of death through December 31, 2016. Stratified analyses explored RSP prevalence by demographic and clinical variables and trade. Log-binomial regression models explored RSP risk factors while controlling for important confounders such as smoking, obesity, and comorbidities. Cox regression models explored mortality risk by spirometry category. Prevalence of RSP was very high (28.6%). Mortality hazard ratios for RSP were 1.50 for all causes, 1.86 for cardiovascular diseases, 2.31 for respiratory diseases, and 1.66 for lung cancer. All construction trades except painters, machinists, and roofers had significantly elevated risk for RSP compared to our internal reference group. RSP was significantly associated with both parenchymal and pleural changes seen by chest X-ray. Construction trade workers are at significantly increased risk for RSP independent of obesity. Individuals with RSP are at increased risk for all-cause mortality as well as mortality attributable to respiratory diseases, cardiovascular diseases, and lung cancer. RSP deserves greater attention in occupational medicine and epidemiology.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Elucidating nanoscale mechanical properties of diabetic human adipose tissue using atomic force microscopy

Abstract Obesity-related type 2 diabetes (DM) is a major public health concern. Adipose tissue metabolic dysfunction, including fibrosis, plays a central role in DM pathogenesis. Obesity is associated with changes in adipose tissue extracellular matrix (ECM), but the impact of these changes on adipose tissue mechanics and their role in metabolic disease is poorly defined. This study utilized atomic force microscopy (AFM) to quantify difference in elasticity between human DM and non-diabetic (NDM) visceral adipose tissue. The mean elastic modulus of DM adipose tissue was twice that of NDM adipose tissue (11.50 kPa vs. 4.48 kPa) to a 95% confidence level, with significant variability in elasticity of DM compared to NDM adipose tissue. Histologic and chemical measures of fibrosis revealed increased hydroxyproline content in DM adipose tissue, but no difference in Sirius Red staining between DM and NDM tissues. These findings support the hypothesis that fibrosis, evidenced by increased elastic modulus, is enhanced in DM adipose tissue, and suggest that measures of tissue mechanics may better resolve disease-specific differences in adipose tissue fibrosis compared with histologic measures. These data demonstrate the power of AFM nanoindentation to probe tissue mechanics, and delineate the impact of metabolic disease on the mechanical properties of adipose tissue.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients

Abstract Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Diabetes and hypertension are related to amyloid-beta burden in the population-based Rotterdam Study

Abstract Higher vascular disease burden increases the likelihood of developing dementia, including Alzheimer’s disease. Better understanding the association between vascular risk factors and Alzheimer’s disease pathology at the predementia stage is critical for developing effective strategies to delay cognitive decline. In this work, we estimated the impact of six vascular risk factors on the presence and severity of in vivo measured brain amyloid-beta (Aβ) plaques in participants from the population-based Rotterdam Study. Vascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, physical inactivity and smoking) were assessed 13 (2004–2008) and 7 years (2009–2014) prior to 18F-florbetaben PET (2018–2021) in 635 dementia-free participants. Vascular risk factors were associated with binary amyloid PET status or continuous PET readouts (standard uptake value ratios, SUVrs) using logistic and linear regression models, respectively, adjusted for age, sex, education, APOE4 risk allele count and time between vascular risk and PET assessment. Participants’ mean age at time of amyloid PET was 69 years (range: 60–90), 325 (51.2%) were women and 190 (29.9%) carried at least one APOE4 risk allele. The adjusted prevalence estimates of an amyloid-positive PET status markedly increased with age [12.8% (95% CI 11.6; 14) in 60–69 years versus 35% (36; 40.8) in 80–89 years age groups] and APOE4 allele count [9.7% (8.8; 10.6) in non-carriers versus 38.4% (36; 40.8) to 60.4% (54; 66.8) in carriers of one or two risk allele(s)]. Diabetes 7 years prior to PET assessment was associated with a higher risk of a positive amyloid status [odds ratio (95% CI) = 3.68 (1.76; 7.61), P < 0.001] and higher standard uptake value ratios, indicating more severe Aβ pathology [standardized beta = 0.40 (0.17; 0.64), P = 0.001]. Hypertension was associated with higher SUVr values in APOE4 carriers (mean SUVr difference of 0.09), but not in non-carriers (mean SUVr difference 0.02; P = 0.005). In contrast, hypercholesterolaemia was related to lower SUVr values in APOE4 carriers (mean SUVr difference −0.06), but not in non-carriers (mean SUVr difference 0.02). Obesity, physical inactivity and smoking were not related to amyloid PET measures. The current findings suggest a contribution of diabetes, hypertension and hypercholesterolaemia to the pathophysiology of Alzheimer’s disease in a general population of older non-demented adults. As these conditions respond well to lifestyle modification and drug treatment, further research should focus on the preventative effect of early risk management on the development of Alzheimer’s disease neuropathology.

van Arendonk, Joyce (ORCID:0000000172941633)↗
DOE OSTI2020

The effect of school intervention programs on the body mass index of adolescents: a systematic review with meta-analysis

Abstract Effective obesity interventions in adolescent populations have been identified as an immediate priority action to stem the increasing prevalence of adult obesity. The purpose of this meta-analysis was to make a quantitative analysis of the impact of school-based interventions on body mass index during adolescence. Studies were retrieved from PubMed, Scopus, Science Direct and Web of Science databases. Results were pooled using a random-effects model with 95% confidence interval considered statistically significant. Of the 18 798 possible relevant articles identified, 12 articles were included in this meta-analysis. The global result showed a low magnitude effect, though it was statistically significant (N = 14 428), global e.s. = −0.055, P = 0.004 (95% CI = −0.092, −0.017). Heterogeneity was low among the studies (I2 = 9.017%). The funnel plot showed no evidence of publication bias. The rank-correlation test of Begg (P = 0.45641) and Egger’s regression (P = 0.19459) confirmed the absence of bias. This meta-analysis reported a significant effect favoring the interventions; however, future research are needed since the reported the evidence was of low magnitude, with the studies following a substantial range of approaches and mostly had a modest methodological quality.

Saavedra Dias, R.↗
DOE OSTI2025

Actinomycetota isolated from the sponge Hymeniacidon perlevis as a source of novel compounds with pharmacological applications: diversity, bioactivity screening, and metabolomic analysis

Abstract Aims To combat health conditions, such as multi-resistant bacterial infections, cancer, and metabolic diseases, new drugs need to be urgently found and, in this respect, marine Actinomycetota have a high potential to produce secondary metabolites with pharmacological importance. We aimed to study the cultivable Actinomycetota community associated with a marine sponge from the Portuguese coast, Hymeniacidon perlevis, and investigate the potential of the retrieved isolates to produce compounds with antimicrobial, anticancer and anti-obesity properties. Methods and results The analysis of the 16S rRNA gene revealed 79 Actinomycetota isolates affiliated with 12 genera—Brachybacterium, Dietzia, Glutamicibacter, Gordonia, Micrococcus, Micromonospora, Nocardia, Nocardiopsis, Paenoartrhobacter, Rhodococcus, Streptomyces, and Tsukamurella, most of which affiliated with the genus Streptomyces. The screening of antimicrobial activity revealed 13 strains, all belonging to the Streptomyces genus, capable of inhibiting the growth of Candida albicans, Bacillus subtilis, or Staphylococcus aureus. Forty-three extracts exhibited cytotoxic activity against at least one tested cell line (HepG2, HCT-116, and hCMEC-D3). Three extracts that were active against the two cancer cell lines tested, did not reduce the viability of the non-cancer endothelial cell line, hCMEC-D3. One Gordonia strain exhibited anti-obesity activity, revealed by its ability to reduce the neutral lipids in zebrafish larvae. Mass spectrometry-based dereplication analysis of active extracts identified several compounds associated with known Actinomycetota natural products. Nonetheless, five clusters contained metabolites that did not match any annotated natural products, suggesting they may represent new bioactive molecules. Conclusions This work contributed to increase the knowledge on the diversity and bioactive potential of Actinomycetota associated with H. perlevis.

Fonseca, Ana C.↗
DOE OSTI2021

Quantile-Dependent Expressivity of Serum Uric Acid Concentrations

“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., serum uric acid) is high or low relative to its distribution. Analyses were performed to test whether serum uric acid heritability is quantile-specific and whether this could explain some reported gene-environment interactions. Methods. Serum uric acid concentrations were analyzed from 2151 sibships and 12,068 offspring-parent pairs from the Framingham Heart Study. Quantile-specific heritability from offspring-parent regression slopes (β OP , h 2 = 2β OP /(1 + r spouse )) and full-sib regression slopes (β FS ,h 2 = {(1 + 8r spouse β FS ) 0.5 - 1}/(2r spouse ) was robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. Results. Quantile-specific h 2 (±SE) increased with increasing percentiles of the offspring’s sex- and age-adjusted uric acid distribution when estimated from β OP (P trend = 0.001): 0.34 ± 0.03 at the 10th, 0.36 ± 0.03 at the 25th, 0.41 ± 0.03 at the 50th, 0.46 ± 0.04 at the 75th, and 0.49 ± 0.05 at the 90th percentile and when estimated from β FS (P trend = 0.006). This is consistent with the larger genetic effect size of (1) the SLC2A9 rs11722228 polymorphism in gout patients vs. controls, (2) the ABCG2 rs2231142 polymorphism in men vs. women, (3) the SLC2A9 rs13113918 polymorphism in obese patients prior to bariatric surgery vs. two-year postsurgery following 29 kg weight loss, (4) the ABCG2 rs6855911 polymorphism in obese vs. nonobese women, and (5) the LRP2 rs2544390 polymorphism in heavier drinkers vs. abstainers. Quantile-dependent expressivity may also explain the larger genetic effect size of an SLC2A9/PKD2/ABCG2 haplotype for high vs. low intakes of alcohol, chicken, or processed meats. Conclusions. Heritability of serum uric acid concentrations is quantile-specific.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Risk of longer-term endocrine and metabolic conditions in the Deepwater Horizon Oil Spill Coast Guard cohort study – five years of follow-up

Abstract Introduction Long-term endocrine and metabolic health risks associated with oil spill cleanup exposures are largely unknown, despite the endocrine-disrupting potential of crude oil and oil dispersant constituents. We aimed to investigate risks of longer-term endocrine and metabolic conditions among U.S. Coast Guard (USCG) responders to the Deepwater Horizon (DWH) oil spill. Methods Our study population included all active duty DWH Oil Spill Coast Guard Cohort members ( N = 45,224). Self-reported spill exposures were ascertained from post-deployment surveys. Incident endocrine and metabolic outcomes were defined using International Classification of Diseases (9th Revision) diagnostic codes from military health encounter records up to 5.5 years post-DWH. Using Cox proportional hazards regression, we estimated adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for various incident endocrine and metabolic diagnoses (2010–2015, and separately during 2010–2012 and 2013–2015). Results The mean baseline age was 30 years (~ 77% white, ~ 86% male). Compared to non-responders ( n = 39,260), spill responders ( n = 5,964) had elevated risks for simple and unspecified goiter (aHR = 2.09, 95% CI: 1.29–3.38) and disorders of lipid metabolism (aHR = 1.09, 95% CI: 1.00–1.18), including its subcategory other and unspecified hyperlipidemia (aHR = 1.10, 95% CI: 1.01–1.21). The dysmetabolic syndrome X risk was elevated only during 2010–2012 (aHR = 2.07, 95% CI: 1.22–3.51). Responders reporting ever ( n = 1,068) vs. never ( n = 2,424) crude oil inhalation exposure had elevated risks for disorders of lipid metabolism (aHR = 1.24, 95% CI: 1.00–1.53), including its subcategory pure hypercholesterolemia (aHR = 1.71, 95% CI: 1.08–2.72), the overweight, obesity and other hyperalimentation subcategory of unspecified obesity (aHR = 1.52, 95% CI: 1.09–2.13), and abnormal weight gain (aHR = 2.60, 95% CI: 1.04–6.55). Risk estimates for endocrine/metabolic conditions were generally stronger among responders reporting exposure to both crude oil and dispersants (vs. neither) than among responders reporting only oil exposure (vs. neither). Conclusion In this large cohort of active duty USCG responders to the DWH disaster, oil spill cleanup exposures were associated with elevated risks for longer-term endocrine and metabolic conditions.

Denic-Roberts, Hristina↗
DOE OSTI2023

Impaired cardiac glycolysis and glycogen depletion are linked to poor myocardial outcomes in juvenile male swine with metabolic syndrome and ischemia

Abstract Obesity continues to rise in the juveniles and obese children are more likely to develop metabolic syndrome (MetS) and related cardiovascular disease. Unfortunately, effective prevention and long‐term treatment options remain limited. We determined the juvenile cardiac response to MetS in a swine model. Juvenile male swine were fed either an obesogenic diet, to induce MetS, or a lean diet, as a control (LD). Myocardial ischemia was induced with surgically placed ameroid constrictor on the left circumflex artery. Physiological data were recorded and at 22 weeks of age the animals underwent a terminal harvest procedure and myocardial tissue was extracted for total metabolic and proteomic LC/MS–MS, RNA‐seq analysis, and data underwent nonnegative matrix factorization for metabolic signatures. Significantly altered in MetS versus. LD were the glycolysis‐related metabolites and enzymes. In MetS compared with LD Glycogen synthase 1 (GYS1)‐glycogen phosphorylases (PYGM/PYGL) expression disbalance resulted in a loss of myocardial glycogen. Our findings are consistent with the concept that transcriptionally driven myocardial changes in glycogen and glucose metabolism‐related enzymes lead to a deficiency of their metabolite products in MetS. This abnormal energy metabolism provides insight into the pathogenesis of the juvenile heart in MetS. This study reveals that MetS and ischemia diminishes ATP availability in the myocardium via altering the glucose‐G6P‐pyruvate axis at the level of metabolites and gene expression of related enzymes. The observed severe glycogen depletion in MetS coincides with disbalance in expression of GYS1 and both PYGM and PYGL. This altered energy substrate metabolism is a potential target of pharmacological agents for improving juvenile myocardial function in MetS and ischemia.

Broadwin, Mark↗
DOE OSTI2023

Deletion of Carboxypeptidase E in β-Cells Disrupts Proinsulin Processing but Does Not Lead to Spontaneous Development of Diabetes in Mice

Carboxypeptidase E (CPE) facilitates the conversion of prohormones into mature hormones and is highly expressed in multiple neuroendocrine tissues. Carriers of CPE mutations have elevated plasma proinsulin and develop severe obesity and hyperglycemia. We aimed to determine whether loss of Cpe in pancreatic β-cells disrupts proinsulin processing and accelerates development of diabetes and obesity in mice. Pancreatic β-cell–specific Cpe knockout mice (βCpeKO; Cpe fl/fl x Ins1 Cre/+ ) lack mature insulin granules and have elevated proinsulin in plasma; however, glucose-and KCl-stimulated insulin secretion in βCpeKO islets remained intact. High-fat diet–fed βCpeKO mice showed weight gain and glucose tolerance comparable with those of Wt littermates. Notably, β-cell area was increased in chow-fed βCpeKO mice and β-cell replication was elevated in βCpeKO islets. Transcriptomic analysis of βCpeKO β-cells revealed elevated glycolysis and Hif1α-target gene expression. On high glucose challenge, β-cells from βCpeKO mice showed reduced mitochondrial membrane potential, increased reactive oxygen species, reduced MafA, and elevated Aldh1a3 transcript levels. Following multiple low-dose streptozotocin injections, βCpeKO mice had accelerated development of hyperglycemia with reduced β-cell insulin and Glut2 expression. In conclusion, these findings suggest that Cpe and proper proinsulin processing are critical in maintaining β-cell function during the development of hyperglycemia.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

The association between neighborhood obesogenic factors and prostate cancer risk and mortality: the Southern Community Cohort Study

Background: Prostate cancer is one of the leading causes of cancer-related mortality among men in the United States. We examined the role of neighborhood obesogenic attributes on prostate cancer risk and mortality in the Southern Community Cohort Study (SCCS). Methods: From the total of 34,166 SCCS male participants, 28,356 were included in the analysis. We assessed the relationship between neighborhood obesogenic factors [neighborhood socioeconomic status (nSES) and neighborhood obesogenic environment indices including the restaurant environment index, the retail food environment index, parks, recreational facilities, and businesses] and prostate cancer risk and mortality by controlling for individual-level factors using a multivariable Cox proportional hazards model. We further stratified prostate cancer risk analysis by race and body mass index (BMI). Results: Median follow-up time was 133 months [interquartile range (IQR): 103, 152], and the mean age was 51.62 (SD: ± 8.42) years. There were 1,524 (5.37%) prostate cancer diagnoses and 98 (6.43%) prostate cancer deaths during follow-up. Compared to participants residing in the wealthiest quintile, those residing in the poorest quintile had a higher risk of prostate cancer (aHR = 1.32, 95% CI 1.12–1.57, p = 0.001), particularly among non-obese men with a BMI < 30 (aHR = 1.46, 95% CI 1.07–1.98, p = 0.016). The restaurant environment index was associated with a higher prostate cancer risk in overweight (BMI ≥ 25) White men (aHR = 3.37, 95% CI 1.04–10.94, p = 0.043, quintile 1 vs. None). Obese Black individuals without any neighborhood recreational facilities had a 42% higher risk (aHR = 1.42, 95% CI 1.04–1.94, p = 0.026) compared to those with any access. Compared to residents in the wealthiest quintile and most walkable area, those residing within the poorest quintile (aHR = 3.43, 95% CI 1.54–7.64, p = 0.003) or the least walkable area (aHR = 3.45, 95% CI 1.22–9.78, p = 0.020) had a higher risk of prostate cancer death. Conclusion: Living in a lower-nSES area was associated with a higher prostate cancer risk, particularly among Black men. Restaurant and retail food environment indices were also associated with a higher prostate cancer risk, with stronger associations within overweight White individuals. Finally, residing in a low-SES neighborhood or the least walkable areas were associated with a higher risk of prostate cancer mortality.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Transcriptomic Analysis of Arachidonic Acid Pathway Genes Provides Mechanistic Insight into Multi-Organ Inflammatory and Vascular Diseases

Arachidonic acid (AA) metabolites have been associated with several diseases across various organ systems, including the cardiovascular, pulmonary, and renal systems. Lipid mediators generated from AA oxidation have been studied to control macrophages, T-cells, cytokines, and fibroblasts, and regulate inflammatory mediators that induce vascular remodeling and dysfunction. AA is metabolized by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) to generate anti-inflammatory, pro-inflammatory, and pro-resolutory oxidized lipids. As comorbid states such as diabetes, hypertension, and obesity become more prevalent in cardiovascular disease, studying the expression of AA pathway genes and their association with these diseases can provide unique pathophysiological insights. In addition, the AA pathway of oxidized lipids exhibits diverse functions across different organ systems, where a lipid can be both anti-inflammatory and pro-inflammatory depending on the location of metabolic activity. Therefore, we aimed to characterize the gene expression of these lipid enzymes and receptors throughout multi-organ diseases via a transcriptomic meta-analysis using the Gene Expression Omnibus (GEO) Database. In our study, we found that distinct AA pathways were expressed in various comorbid conditions, especially those with prominent inflammatory risk factors. Comorbidities, such as hypertension, diabetes, and obesity appeared to contribute to elevated expression of pro-inflammatory lipid mediator genes. Our results demonstrate that expression of inflammatory AA pathway genes may potentiate and attenuate disease; therefore, we suggest further exploration of these pathways as therapeutic targets to improve outcomes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Urban Green Spaces, Greenness Exposure and Species Richness in Residential Environments and Relations with Physical Activity and BMI in Portuguese Adolescents

Environmental factors play an important role in obesity-related behaviors. Evidence indicates significant associations between weight and urban green spaces in adults, but it is not clear whether this relationship applies to adolescents. Therefore, our aim was to determine the associations between urban green spaces, greenness exposure and species richness in residential environments with physical activity and body mass index. Sixty-two adolescents between 12 and 18 years of age answered a self-administered questionnaire, providing information on height, weight, age, sex and home address. Data on socioeconomic deprivation were obtained from the European Index of Deprivation for Small Portuguese Areas. Physical activity levels were assessed using accelerometers. Urban green space counts and the normalized difference vegetation index values were measured using buffers along the roads with distances of 300, 500, 1000 and 1500 m from each participant’s residence. To quantify the species richness, the species richness index was used. Linear regression models were fitted to analyze whether urban green spaces, exposure to green spaces and species richness counts for each distance were associated with physical activity and self-reported body mass index. We did not find significant associations between the independent variables and the probability of overweight or obesity. The relationship between environmental variables, adolescents’ physical activity and body weight seems to be complex and further studies may contribute to better understanding of the topic.

Melo, Juliana (ORCID:0000000301275340)↗