bluuebunny/crossref_metadata_2025_split huggingface dataset:
General Control Nonderepressible 2 (GCN2) Kinase Regulates Body Composition and Antioxidant Defenses during Dietary Methionine Restriction.
Authors: Pettit Ashley P. , Bargoud Albert , Mirek Emily T. , Anthony Tracy G. 
Published: June 2021

Dietary methionine restriction (MR) produces physiological responses associated with resistance to metabolic disease and increased lifespan, but the sensing mechanism remains to be established. As a part of the integrated stress response pathway (ISR), the eukaryotic initiation factor 2 (eIF2) kinase GCN2 is a sensor of amino acid insufficiency by diet, drug or genetics. We hypothesized that phosphorylation of eIF2 (eIF2~P) by GCN2 mediates the metabolic phenotype by dietary MR. C57Bl/6J wildtype mice (WT) or mice deleted for Gcn2 (KO) were fed an obesity‐promoting diet (60% kcal fat) sufficient in methionine (0.86% kcal met, CON) for 1 week. Mice then remained on CON or were switched to an obesity‐promoting diet restricted in methionine (0.12% kcal met, MR) for an additional 5 weeks (n=6–8 per group). Results were evaluated by 2 factor ANOVA and Tukey post hoc with a significance level set at p<0.05. MR reduced body weight in WT and KO mice similarly (↓22%) even though MR mice consumed more energy (↑13%) than CON mice. WTMR mice also lost a significant amount of body fat (↓15%) as compared to WTCON but surprisingly, KOMR mice lost an insignificant amount of body fat as compared to KOCON (↓4%). Consistent with this difference in body composition, subcutaneous fat weights were decreased ~60% in WTMR as compared to WTCON but unchanged in KOMR as compared to KOCON. In the liver, activation of the ISR was indicated in both WTMR and KOMR via eIF2~P. MR also induced ISR genes Atf5, Atf3, Asns, Fgf21 and a profile of antioxidant genes including Ho1 and Nqo1 regardless of GCN2 status. On the other hand, MR reduced expression of fatty acid synthesis genes Fasn and Scd1 to a greater extent in the liver of WT versus KO mice. Furthermore, expression of the hepatic antioxidant defense gene Sod2 was increased in WTMR but not KOMR. These results indicate that GCN2 contributes to but is not a primary sensor of MR because activation of the ISR in the liver and reduction of body weight occurred largely independent of GCN2. However, certain physiological outcomes such as body composition and mitochondrial oxidative defenses in the liver were influenced by GCN2 status. Our study provides new insights into the GCN2 dependent and independent mechanisms by which MR alters metabolism and cellular defenses.Support or Funding InformationNIH HD070487, USDA NIFA NC1184, INSPIRE at Rutgers, Rutgers University
Impact of Imposed Exercise on Children's Ad Libitum Energy Intake
Authors: Fearnbach Stephanie Nicole , Masterson Travis D , Schlechter Haley A , Downs Danielle Symons , Thivel David , Keller Kathleen L 
Published: June 2021

Determining strategies to decrease energy intake (EI) and promote energy expenditure (EE) is of utmost importance to prevent childhood obesity. Exercise not only has a direct effect on energy balance through EE, but also has an indirect effect through its impact on EI. Previous studies in adolescents with obesity have demonstrated that exercise, relative to rest, is effective in reducing subsequent EI and overall energy balance. From a prevention standpoint, it is vital to determine the effectiveness of exercise‐related strategies to reduce overeating in children who are healthy weight, but are at risk for developing obesity due to family history. This study examined the effects of acute exercise on EI in 18 healthy‐weight children (ages 9–12 years, n = 11 male) with at least 1 overweight biological parent (body mass index ≥ 25 kg/m2). Children reported to the laboratory for 1 baseline and 2 experimental visits (EX = exercise, SED = sedentary) each separated by 1 week in a randomized crossover design. Two hours into the EX day session, children exercised at 70% estimated VO2peak for 30 minutes on a cycle ergometer. Objective EI (kcal) was measured at a standard breakfast (285 kcal) and ad libitum lunch, snack, and dinner. Meals were identical on the EX and SED days. Activity‐related EE (kcal) was estimated with ActiGraph GT3X‐BT accelerometers worn on the non‐dominant wrist and ankle, scored using ActiLife 6 software. Relative EI (kcal) was computed as the difference between total EI and activity‐related EE for each testing day. Paired t‐tests were performed to test differences in total EI, activity‐related EE, and relative EI between the EX and SED days, analyzed using SPSS. Across all meals, total EI was not statistically different between the EX and SED days (t = 0.47, p = 0.64). Total intake on the two days was highly correlated (r = 0.83, p < 0.01). Activity‐related EE was greater on the EX day compared to the SED day (t = 9.18, p < 0.001). By design, this difference was predominantly driven by activity during the morning (t = 18.20, p < 0.001). Because children ate a similar number of kcal on each day, but had greater activity‐related EE on the EX day, relative EI was lower (t = −5.37, p < 0.001) for the EX day (1429 ± 354 kcal) relative to the SED day (1714 ± 296 kcal). Children did not adjust their daily EI to reflect differences in activity‐related EE between the two days, resulting in over‐consumption on the SED day compared to the EX day. Imposed exercise may help at‐risk children to better regulate their food intake within the course of a day.Support or Funding InformationSupported by USDA/NIFA Grant #2011‐67001‐30117 Program A2121.
Effects of dietary protein and fiber at breakfast on postprandial appetite, neural responses to visual food stimuli, and ad libitum energy intake at lunch in overweight adults
Authors: Sayer R Drew , Amankwaah Akua , Tamer Gregory , Chen Ningning , Wright Amy , Tregellas Jason , Cornier Marc , Kareken David , Talavage Thomas , McCrory Megan , Campbell Wayne 
Published: June 2021

Increasing either protein or fiber at mealtimes has relatively modest effects on satiety and ingestive behavior. Whether increasing protein and fiber in the same meal has additive or interactive effects on ingestive behavior is not known. Five female and 10 male overweight (BMI: 27.1 ± 0.2 kg/m2) young adults (26 ± 1 y) were provided with breakfast meals of varying protein and fiber amounts (normal protein [12.5 g] + normal fiber [3 g], normal protein [12.5 g] + high fiber [8 g], high protein [25 g] + normal fiber [3 g], high protein [25 g] + high fiber [8 g]) during 4, 2‐week interventions in a randomized crossover manner. At the end of each intervention, fasting and postprandial appetite ratings, neural responses to visual food stimuli, and ad libitum energy intake at lunch were collected. A priori reward‐related brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fiber intake at breakfast did not affect ingestive behavior outcomes. Higher protein intake at breakfast transiently decreased desire to eat 60 minutes after breakfast, but did not influence hunger, fullness, or energy intake at lunch. Compared to fasting‐state, right insula responses to visual food stimuli were decreased 180 min after consuming normal protein, but not high protein, breakfasts. In conclusion, these data do not support increasing dietary protein and fiber at breakfast as effective strategies for modulating neural reward processing and ingestive behavior in overweight adults.Support or Funding InformationAmerican Egg Board, NIH UL1 TR001108, USDA‐NIFA 2011‐38420‐20038, Purdue University Ingestive Behavior Research Center
Reversal Effects of Genistein and (−)‐Epigallocatechin‐3‐Gallate on Repression of BRCA‐1 Expression in Human Breast Cancer Cells with Activated AhR
Authors: Selmin Ornella I , Papoutsis Andreas J , Romagnolo Donato F 
Published: June 2021

Sporadic breast cancers, which represent the vast majority (~90%) of breast tumor cases, do not have mutations in the tumor suppressor gene, BRCA‐1 but have absent or markedly reduced levels of BRCA‐1 similar to those observed in hereditary BRCA‐1 tumors. Therefore, understanding the non‐mutational mechanisms that contribute to silencing of BRCA‐1 has important implications for the prevention of both hereditary and sporadic breast tumors. Agonists of the aromatic hydrocarbon receptor (AhR) are ubiquitous in the environment and include dietary compounds, metabolites of fatty acids, industrial pollution, and photoproducts generated in the skin from ultraviolet radiation. In cultured estrogen‐receptor (ER)α‐positive MCF‐7 breast cancer cells, we found that the BRCA‐1 gene is a molecular target for activation by estradiol. In contrast, the cotreatment with equimolar (10 nM) concentrations of the prototype AhR‐ligand 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin (TCDD) repressed by 50% estrogen‐induced BRCA‐1 protein expression. The post‐treatment with the soy isoflavone genistein and tea (−)‐epigallocatechin‐3‐gallate (EGCG) at physiological doses (1 μM) rescued within 24 to 48 h BRCA‐1 protein expression to levels ~2.0 to 3.0‐fold higher than those measured in cells treated with estradiol. In ERα‐negative/AhR‐overexpressing UACC‐3199 breast cancer cells, genistein increased BRCA‐1 expression in a dose‐dependent fashion (1nM to 1μM). In chromatin immunoprecipitation assays with MCF‐7 cells, the post‐treatment with genistein and EGCG antagonized the TCDD‐induced recruitment of DNA‐methyl transferase‐1 (DNMT‐1) enzyme at the BRCA‐1 gene. These results suggest the involvement of epigenetic mechanisms in the reactivation of BRCA‐1 expression and preventative effects of genistein and EGCG against breast tumorigenesis associated with exposure to AhR carcinogens.Support or Funding InformationThis work was supported by grants from the Arizona Biomedical Research Commission (QSR14082995), the US Department of Defense Breast Cancer Program (BC134119), and Soy Health Research Foundation.
A High Flavonoid Diet Reduces Gut Permeability, Short Chain Fatty Acid Production and Decreases Gut Inflammation in Overweight and Obese Men and Women
Authors: Ward Robert Edwin , Bergerson Janet , Hergert Nancie , Hergert John , Aguilar Sheryl , Khan Abdullah , Kung Stephanie , Lefevre Michael 
Published: June 2021

We hypothesized that providing a diet high in flavonoids would reduce gut permeability, and gut inflammation, and possibly differentially affect the fecal concentrations of short chain fatty acids (SCFA). To test this hypothesis, 29 overweight/obese (BMI; 25.2–34.5 kg/m2) men (N=16) and women (N=16) were provided two well‐controlled diets that were identical in macronutrient content (Protein 17% en; Fat, 30% en, Carbohydrate, 53% en), but formulated to have large differences in the flavonoid content. The Low Flavonoid Diet (LFD) contained 10 mg/1000 Kcals, while the High Flavonoid Diet (HFD) contained 340 mg/1000 Kcals. The study was a randomized cross‐over design with six weeks for each arm, and subjects were provided all meals. Endpoints were determined in duplicate during the last week of each diet period. Gut permeability was assessed by the differential sugar test using mannitol, sucrose, lactulose and sucralose which were measured after ingestion and 24h collection by gas chromatography. Fecal SCFA (acetic, butyric, proprionic, valeric, caproic, isovaleric and isobutyric acids) were measured using gas chromatography. Gut inflammation was determined by measure of fecal calprotectin (Calp), myeloperoxidase (MPO) and eosinophil derived neurotoxin (EDN). Food was well tolerated by participants; compliance was assessed by questionnaires and direct observation and was deemed to be excellent. Compared to the LFD, the HFD significantly reduced gut permeability, with differential effects along the length of the GI tract. Compared to the LFD, sucrose recovery was reduced 45% by the HFD, whereas lactulose and sucralose were reduced by 34% and 22%. Collectively, these data indicate the HFD has a greater effect on gut permeability in proximal gastrointestinal tract. The HFD also significantly reduced the fecal concentration of all seven SCFA in the range of 15 to 50%. For the three most abundant SCFA the reductions were 24% (acetic), 20% (butyric) and 34% (proprionic). Lastly, the HFD also significantly reduced markers of intestinal inflammation by 53% to 72%. Despite significant reductions in both intestinal permeability and inflammation, there was no effect on plasma lipopolysaccharide. Collectively, these data indicate dietary flavonoids have a substantial effect on the barrier properties of the gut, metabolic activity of the microbiome and intestinal inflammation.Support or Funding InformationThis work was supported by USDA/NIFA grant 2014‐67017‐21749.
Use of Skin Carotenoids as a Biomarker for Fruit and Vegetable Intake Among Mexican‐Origin Children in a Community Setting
Authors: Aguilera Alberto Leopoldo , de la Torre Adela , Kaiser Lucia Lynn 
Published: June 2021

Measuring fruit and vegetable (F/V) consumption in individuals is important for evaluating nutrition interventions and population‐based studies. Traditional methods of assessing F/V intake rely on participant recall, which raises concerns of accuracy. Recently, clinical studies using skin carotenoid levels show promising results as an objective measure of F/V intake. However, there is a need to further develop this method in community‐based studies with hard to reach populations. The Niños Sanos, Familia Sana (Healthy Children, Healthy Family) study is a multi‐year, multi‐faceted intervention aimed at reducing obesity rates and increasing F/V consumption among Mexican‐origin children. The purpose of this study was to compare skin carotenoid levels to F/V intake as measured by a food frequency questionnaire (FFQ) and 24‐hour dietary recalls (24HDR). Participants included 51 Mexican‐origin children (ages 3–8 years) from a rural, Central Valley community in California. The researchers measured the skin carotenoid levels of the children were using the Pharmanex BioPhotonic Scanner. Trained bilingual university students interviewed parents in person and over the phone to collect three 24HDR recalls of their children's dietary intake. The researchers calculated the children's F/V intake over 30 previous days a 26‐item, parent‐reported FFQ (including fresh fruit, canned fruit, vegetable soup, other cooked vegetables, salsa, lettuce or cabbage, and other vegetables). Preliminary results of the study demonstrate a significant positive correlation between skin carotenoid levels and parent‐reported 24HDR vegetable consumption (r=0.41, p=0.003) but not with 24HDR fruit, FFQ fruit, or FFQ vegetable consumption. The use of skin carotenoid measurements may be more indicative of vegetable consumption than overall fruit and vegetable consumption in this population of Mexican‐origin children.Support or Funding InformationFunded by USDA‐NIFA Fund number: 82705
Genetic Ablation of TNF‐α Attenuates High Fat Diet‐induced Obesity Potentially via Diminishing Wnt‐signaling and Determinant Genes of Adipogenesis
Authors: Li Jinchao , Frederick Armina‐Lyn , Kim Young‐Cheul , Wood Richard J. , Liu Zhenhua 
Published: June 2021

Recent decades have seen a rapid increase in obesity, which is associated with increased risk of multiple medical complications including diabetes, cardiovascular disease, and some cancers. As obesity has reached an epidemic level and no decrease is projected in the near future, new prevention and medication strategies are needed for obesity and related disorders. Tumor necrosis factor alpha (TNF‐α), a critical pro‐inflammatory cytokine, is elevated in adipose tissue and its expression level correlates with the degree of obesity. Impressive evidence shows that diets or drugs, which are used to reduce inflammation, can ameliorate obesity. The objective of the study was to investigate the role of TNF‐α in high‐fat diet‐induced obesity and thereby to examine the potential implication of targeting TNF‐α in obesity and obesity‐related complications. Fifty‐two wildtype and 52 TNF‐α knockout mice (male and female evenly) with the same C57BL6 genetic background were randomly divided into two groups receiving either a high‐fat diet (HFD, 60% fat) or a low fat diet (LFD, 10% fat) for 16 weeks. Body weight were monitored weekly and body composition were determined by Magnetic Resonance Imaging (MRI), The expression of pro‐inflammatory cytokines, key components within Wnt pathway and determinants of adipogenesis in the visceral adipose tissue were also measured. The results shows that, while there are no significant differences among the LFD groups (p > 0.05), wildtype HFD group has significantly higher body weight and fat composition compared to TNF‐α knockout HFD group. In addition to TNF‐α itself, the expressions of IL‐6 and IFNγ, as measured by chemiluminescent immunoassay, were also significantly lower in the HFD‐induced obese animals with TNF‐α knockout when comparing to the wildtype HFD group (p < 0.05). In the obese state, the genetic ablation of TNF‐α significantly reduced Wnt‐signaling, as indicated by decreased phospho‐GSK3β and active β‐catenin as well as Wnt pathway downstream genes (p < 0.05). The deletion of TNF‐α significantly increased both mRNA and protein expression of PPARγ and C/EBPα, two critical genes which are key determinants of adipogenesis. All these data collectively indicate that depletion of TNF‐α may ameliorate HFD‐induced obesity, potentially via altering Wnt‐signaling and determinants of adipogenesis.Support or Funding InformationThis project is supported by USDA grants (2014‐67017‐21762 and MAS00454) and the Pilot grant from Rays of Hope Center for Breast Cancer Research
Increasing Physical Activity in American Indian Adults: Preliminary Results from a Multi‐institutional Obesity Prevention Program
Authors: Redmond Leslie , Eckmann Thomas , Pardilla Marla , Swartz Jacqueline , Platero Harrison , Gittelsohn Joel 
Published: June 2021

BackgroundPrevalence of obesity is disproportionately high among American Indians (AIs) and is associated with increased prevalence of diabetes, hypertension, and cardiovascular disease. Increasing physical activity (PA) is associated with weight loss and maintenance of a healthy body weight.ObjectiveThe objective of this study was to decrease obesity and promote healthier bodyweights using a multi‐level, multi‐institutional obesity intervention designed to increase knowledge, build self‐efficacy, and influence intentions for improved behavior change at multiple levels. Primary areas of focus were nutrition, PA, and behaviors related to food consumption and purchasing. The aim of this analysis was to determine whether or not participants in the intervention communities engaged in a greater amount of PA versus comparison at follow‐up.MethodsA randomized controlled community‐based program (OPREVENT) was developed, implemented, and evaluated within five AI communities. The five communities were randomly assigned to intervention (n=3) or delayed intervention (comparison; n=2)in New Mexico and Michigan. A modified International Physical Activity Questionnaire‐Short Form (IPAQ‐SF) was administered to 180 randomly selected community members at baseline and follow‐up from intervention and comparison communities.ResultsTotal days per week participating in vigorous PA was significantly different between intervention and comparison at follow‐up (p<0.05). Total Metabolic Equivalents(METs) of vigorous PA was significantly different between intervention and comparison at follow‐up (p<0.05).ConclusionsOPREVENT was associated with an increase in days per week engaged invigorous PA as well as an increase in total METs vigorous PA in communities that received the OPREVENT program.Support or Funding InformationThe USDA provided funding for this project. Approval and support was obtained from all participating tribal communities.
Level of tool‐use proficiency in chimpanzees is associated with differences in gray matter distribution in the inferior parietal cortex: a voxel‐based morphometry study
Authors: Reyes Laura Denise , Hopkins William D , Sherwood Chet C 
Published: June 2021

Evidence from paleoneurology and neuroimaging studies suggests that the inferior parietal region expanded in the human lineage. We compared gray matter distribution in MRI scans of chimpanzees with high and low proficiency at tool‐use with voxel‐based morphometry (VBM) to assess the link between tool‐use and structural differences in the inferior parietal cortex (IPC). The sample consisted of nine high proficiency (HP) and nine low proficiency (LP) female chimpanzee tool‐users to avoid a possible sex bias. Tool‐use proficiency was based on Z‐scores for average performance time on a simulated termite‐fishing task; Z‐scores greater than or equal to 0.5 standard deviations above and below the mean were classified as HP and LP, respectively. A VBM analysis focused on the IPC showed significantly increased gray matter in HP compared to LP tool‐users in the left supramarginal gyrus (SMG; X=43, Y=75, Z=79; p < 0.05). The left SMG is part of a left‐lateralized network involved in human tool‐use, and its anterior portion is activated during tool‐use in humans but not macaques. SMG activation is also observed during expert stone tool‐making in humans. These results indicate that there are structural differences in the IPC based on tool‐use proficiency in this sample of chimpanzees, suggesting that cortical variation associated with tool‐use and tool‐making predated the evolution of the genus Homo. and could have provided a basis for the evolution of stone tool‐making in the human lineage.Support or Funding InformationNSF BCS‐1455629, NSF DGE‐0801634, James S. McDonnell Foundation 22002078, James S. McDonnell Foundation 220020293, NIH NS‐ 73134, NIH NS ‐ 42867
Regulation of the Development of Human Neurons by Substratum Elasticity
Authors: Rivera‐Pérez Luis Miguel , Nichol Robert , Gomez Timothy 
Published: June 2021

Growth cones, the sensory tips of developing axons, respond to molecular cues present in the environment. Additionally, recent studies suggest local differences in environmental rigidity affect axon development via mechanosensitive protein regulation in growth cones, and is dependent upon neuronal subtype. Neurites innervating the Central Nervous System (CNS) grow more rapidly on flexible substrata. Conversely, neurites projecting into the Peripheral Nervous System (PNS) prefer rigid substrata. By using human forebrain (hFBs) and motor neurons (hMNs) differentiated from Induced Pluripotent Stem Cells (IPSCs), we compared growth rates and morphology of CNS and PNS neurons on varying substrata stiffnesses. We found MNs prefer more rigid substrata, while forebrain neurons do not have a strong preference for rigidity. Finally, we found both hFBs and hMNs express mechanosensitive ion channels. Future studies should investigate differential expression patterns of these ion channels on different rigidities as a possible mechanism for the differential growth we observed.Support or Funding InformationNIH RO1NS41564‐10 (to T.M.G)NIH T32GM007507 (to UW‐NTP)IBS‐SRP at UW‐Madison (NSF grant NSF‐DBI 1063085)NIH‐NIGMS R25GM096955 (to Edu B. Suarez‐Martinez)