bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 22 bp FADS2 Insertion‐Deletion (Indel) Polymorphism Influences Arachidonic Acid Status
Authors: Kothapalli Kumar S.D , Gadgil Maithili S. , Carlson Susan E. , O'Brien Kimberly O. , Ye Kaixiong , Zhang Ji Yao , Park Hui Gyu , Ojukwu Kinsley , Zou James , Hyon Stephanie S. , Joshi Kalpana S. , Keinan Alon , Brenna J. Thomas 
Published: November 2023

IntroductionThe fatty acid desaturase 2 (FADS2) gene product catalyzes a key step in the biosynthesis of biologically active long chain polyunsaturated fatty acids (LCPUFA). The rs66698963 a 22 bp polymorphic insertion‐deletion (Indel) is associated with basal expression of FADS1 which mediates the Δ5‐desaturation of dihomo‐gamma‐linolenic acid to arachidonic acid (20:3n‐6→20:4n‐6), as well as coordinated induction of FADS1 and FADS2 expression in vitro. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage.MethodsA total of 234 individuals of a primarily vegetarian Indian population and 311 individuals from the U.S were genotyped. Evolutionary analysis testing for positive selection on the FADS region was performed using genetic variations data from the 1000 Genomes Project (1000GP). Functional analysis of rs66698963 genotypes and fatty acid levels was evaluated in a subset of the U.S. population.ResultsA much higher I/I genotype frequency was found in Indians (68%) than in the U.S. (18%). Data from 1000 Genomes Project confirmed our observation and revealed a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Evolutionary analyses revealed for the first time signals of positive selection around rs66698963 in only South Asians. Basal plasma phospholipid arachidonic acid status was 8% greater in I/I compared to D/D individuals. The biochemical pathway product‐precursor difference, arachidonic acid minus linoleic acid, was 31% and 13% greater for I/I and I/D compared to D/D, respectively.ConclusionOur study is consistent with previous in vitro data suggesting that the insertion allele enhances n‐6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant‐based diet practice.Support or Funding InformationR01 AT007003
Anti‐inflammatory and anti‐cancer effects of the colonic metabolites of polymethoxyflavone
Authors: Wang Minqi , Wu Xian , Song Mingyue , Xiao Hang 
Published: November 2023

Polymethoxyflavones (PMFs) are unique flavonoids found in citrus fruits, and they have been shown to possess protective effects against inflammation‐associated colon carcinogenesis in mice. To further understand the molecular mechanism underlying these effects, we characterized the colonic metabolites of PMFs in mice fed with two major citrus PMFs, i.e. nobiletin (NOB) and 5‐demethoxylnobiletin (5DN) respectively (0.1% in the diet for 20 weeks). Multiple demethylated metabolites of NOB and 5DN were identified in the colonic mucosa. Interestingly, the abundance of these metabolites in the colon was much higher than that of the parent compounds. Mixture of colonic metabolites were isolated from feces, and subject to in vitro tests for anti‐inflammatory and anti‐cancer effects. It was found that the fecal isolates potently inhibited the growth of multiple human colon cancer cells, and suppressed the lipopolysaccharide‐induced inflammation in macrophages. It is noteworthy that the aforementioned biological effects of the fecal isolates were observed at the achievable levels of metabolites found in the colonic tissues of mice fed with PMFs, and these effects were hundreds folds more potent than those of the parent compounds alone. Overall, this study revealed that the colonic metabolites of PMFs, rather than the PMFs themselves, were mainly responsible for the protective effects of orally administered PMFs against inflammation and carcinogenesis in the colon.Support or Funding InformationThis study was supported by funding from NIH, AICR and USDA.
Dietary Sphingomyelin Attenuates Inflammation and Metabolic Dysfunction in Diet‐ Induced Obese Mice
Authors: Norris Gregory H , Porter Caitlin M , Jiang Christina , Blesso Christopher 
Published: November 2023

Current evidence indicates that dietary sphingomyelin (SM) is lipid‐lowering and anti‐inflammatory, although its potential to prevent chronic disease as part of the diet has not been fully explored. SM is not a dietary essential and there is no recommended dietary intake. Consumption of dietary sphingolipids in Western diets is relatively common (0.3–0.4 g/day) and comes mainly from eggs and milk products. However, little is known about an optimal intake of SM and whether an increased dietary intake of SM is beneficial to health. Egg SM (ESM) and milk SM (MSM) differ in their fatty acid and sphingoid base composition, and may have different bioactivities when consumed in the diet. We evaluated the effects of milk and egg SM on diet‐induced obesity in high fat, high cholesterol diet‐fed C57BL/6J mice. We hypothesized that dietary SM would attenuate inflammation and metabolic dysfunction that occurs with obesity. We fed male C57BL/6J mice a high fat, high cholesterol diet (31% lard and 0.2% cholesterol by weight) (CTL; n = 14), or the same diet supplemented with either 0.1% (w/w) egg SM (ESM; n = 14) or 0.1% (w/w) milk SM (MSM; n = 13). After 10 weeks, ESM had gained significantly less weight than CTL reflected by a reduced epididymal adipose weight. ESM had significantly lower plasma cholesterol and fasting glucose when compared with the other groups. Although no significant difference was found in liver weight, H&E staining of both SM groups revealed an attenuation in the development of hepatic steatosis. Both SM groups had significantly lower plasma IFNγ and MCP‐1 compared to CTL. MSM also significantly lowered plasma TNFα, MIP‐1β, and IL‐6 compared to CTL. The reduction in inflammatory markers lead to an exploration of SM effects on macrophage activation. Milk SM significantly blunted LPS induction of both MCP‐1 and TNFα mRNA in RAW264.7 macrophages. These data suggest dietary SM has potential to influence obesity, through inhibiting lipid absorption and inflammation.Support or Funding InformationSupported by the University of Connecticut
Gamma Tocotrienol Suppresses NLRP3 Inflammasome by Dual Mechanism of A20‐ mediated Priming Inhibition and AMPK/autophagy Axis Activation
Authors: Kim Yongeun , Chung Soonkyu 
Published: November 2023

Nod‐like receptor 3 (NLRP3) inflammasome is the intracellular innate immunity sensor that processes and releases IL‐1β in response to microbial invasion or metabolic danger signals such as saturated fatty acids and free cholesterol. Aberrant activation of NLRP3 is intimately associated with numerous chronic inflammatory diseases. However, little information is available as to whether NLRP3 inflammasome is regulated by dietary factors. The aim of this study is to investigate whether gamma‐tocotrienol (γT3), an unsaturated form of vitamin E, downregulates NLRP3 inflammasome activation, and to determine the molecular mechanisms. Pretreatment of γT3 (0.5–10 mM) significantly suppressed activation of NLRP3 inflammasome reporter, caspase‐1 cleavage, and IL‐1β and IL‐18 secretion in J774 macrophages as well as bone marrow‐derived murine macrophages (BMDM). To further determine the mechanisms, we investigate the role of γT3 on NFκB activation and AMPK/autophagy axis activation. γT3 significantly attenuated proinflammatory gene expressions of IL‐1β, IL‐18 and NLRP3, and induced A20 expression, an ubiquitin‐editing enzyme to interrupt NFκB signaling. Induction of A20 concurred with 1) the decrease of p‐IKKα/β, p‐ERK, and p‐IκBα; 2) the reappearance of IκBα, and 3) the disappearance of TRAF6, suggesting a negative feedback of A20 on TRAF6/IKK/NF‐κB signaling. Moreover, silencing of A20 markedly dampened the inflammasome inhibitory effects of γT3. Intriguingly, γT3 treatment was also associated with AMPK/autophagy axis activation shown through LC3II accumulation and increased levels of AMPK phosphorylation. The inhibition of AMPK with Compound C completely reversed γT3's inhibitory role on NLRP3 inflammasome and caspase‐1 cleavage. Taken together, we demonstrated that γT3 suppresses NLRP3 inflammasome by two mechanisms, 1) inhibition of TRAF6/NFκB axis activation through induction of A20, and 2) activation of AMP kinase/autophagy thereby inhibiting inflammasome assembly.Support or Funding InformationAmerican Heart Association
Docosahexaenoic Acid Inhibits Cerulein‐Induced Cytokine Expression by Activating Peroxisome Proliferator‐Activated Receptor γ in Pancreatic Acinar Cells
Authors: Song Eun Ah , Lim Joo Weon , Kim Hyeyoung 
Published: November 2023

Oxidative stress is regarded as a major pathogenic factor in acute pancreatitis. Cerulein pancreatitis is similar to human edematous pancreatitis involving dysregulation of digestive enzyme production, cytoplasmic vacuolization, and increased cytokine production. Previously, we showed that cerulein activates NADPH oxidase to produce reactive oxygens species (ROS). ROS mediate Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and cytokine expression in pancreatic acinar cells. And agonists of peroxisome proliferator‐activated receptor γ (PPARγ) inhibit cerulein‐induced cytokine expression by regulating JAK2/STAT3 in pancreatic acinar cells. Docosahexaenoic acid (DHA) exerts anti‐inflammatory and anti‐oxidant effect. Recently, DHA has been known to activate PPARγ in the cells. PPARs are ligand‐activated transcription factors belonging to nuclear receptor superfamily. PPARγ ligands show anti‐inflammatory activities in various cells by inhibiting the expression of pro‐inflammatory cytokines. PPARγ agonists protect the cells against oxidative stress‐mediated inflammation through reducing ROS levels by inducing antioxidant enzymes such as catalase and GSH peroxidase.The present study is purposed to investigate whether DHA inhibits cerulein‐induced cytokine expression by activating PPARγ and inhibiting JAK2/STAT3 signaling in pancreatic acinar AR42J cells.The cells were pre‐treated with DHA for 2h, and then stimulated with cerulein (10−8 M). In other sets of experiments, the cells were treated with PPARγ agonists (Troglitazone, 15‐Deoxy‐ Δ12,14‐prostaglandin J2) or DHA and PPARγ antagonist GW9662. The mRNA and protein levels of IL‐6 and PPARγ were determined using Real‐time PCR and Western blot analyses. ROS levels were determined using DCF‐DA.The results showed that DHA inhibited cerulein‐induced IL‐6 expression and JAK2/STAT3 activation in AR42J cells. DHA induced the expression of PPARγ. PPARγ agonists inhibited cerulein‐induced IL‐6 expression. DHA reduces the levels of ROS and IL‐6, which was reversed by co‐treatment of PPARγ antagonist in cerulein‐stimulated AR42J cells.In conclusion, DHA inhibits Jak2/Stat3‐mediated IL‐6 expression by activating PPARγ and reducing ROS levels in pancreatic acinar cells. DHA may be beneficial for suppressing the development of pancreatitis by inhibiting cytokine expression in pancreatic acinar cells.Support or Funding InformationThis study was supported by a grant (NRF‐2015R1A2A2A01004855) from the NRF of Korea.
Anti‐inflammatory properties of tangeretin, 5‐demethyltangeretin and their primary metabolites
Authors: Guo Shanshan , Wu Xian , Zheng Jinkai , Dong Ping , Qiu Peiju , Xiao Hang 
Published: November 2023

Inflammation plays important roles in the development of multiple chronic diseases. Increased consumption of anti‐inflammatory nutraceuticals has been considered as a promising strategy to prevent inflammation‐driven diseases. Orally ingested nutraceuticals undergo complex metabolism in the body, which gives rise to various metabolites. As the results, both the parent nutraceuticals and their metabolites may contribute to the overall biological effects. Tangeretin (TAN) and 5‐demethyltangeretin (5DT) are unique flavonoids found in citrus fruits. In mice fed with TAN and 5DT, we identified the primary metabolites of TAN and 5DT as 4′‐ demethyltangeretin (4DT) and xanthomicrol (XAN), respectively. Our results showed that TAN, 5DT and their metabolites exhibited extensive anti‐inflammatory effects in lipopolysaccharide (LPS)‐stimulated RAW 264.7 macrophages. More importantly, 4DT and XAN showed stronger anti‐inflammatory effects than their parent compounds TAN and 5DT. 4DT inhibited LPS‐induced expression of iNOS and COX‐2 by modulating multiple signaling pathways, particularly by suppressing the activation of p38, JNK, and PI3K/Akt, and inhibiting nuclear translocation of NF‐κB. XAN also significantly inhibited LPS‐induced inflammation in RAW 264.7 macrophage, which was evidenced by lowered nitric oxide and PGE2 production, decreased protein levels of iNOS and COX‐2, decreased gene expression of IL‐1β, and increased expression of phase II enzyme HO‐1. Overall, our results showed that TAN and 5DT are promising dietary anti‐inflammatory agents due to the fact that their primary metabolites possess potent anti‐inflammatory activities.Support or Funding InformationThis study was supported by funding from NIH, AICR and USDA.
Effects of a higher vs. lower protein diet on weight loss in teenagers: Results from a randomized controlled trial
Authors: Apolzan John William , Hsia Daniel S , Martin Corby K 
Published: November 2023

ObjectiveTo provide pilot data on weight loss efficacy in overweight and obese adolescents during isocaloric lower vs higher protein weight loss diets utilizing the U.S. Department of Agriculture (USDA) MyPlate nutrition guide.MethodsThirty two, 12–17 year old adolescents with body mass index ≥ 85th percentile were recruited for a 12‐week free‐living weight loss intervention. Participants were randomized to either a lower protein group with 15% of energy as protein and 60% of energy from carbohydrate or a higher protein group with 30% of energy as protein and 45% of energy from carbohydrate. Both diets restricted energy intake by 25%. Dietary counseling was based on the USDA MyPlate guidelines. The first intervention session was individual followed by 6 (biweekly) group sessions. Participants had anthropometric measurements and performed retrospective visual analogue scale (VAS) appetite ratings at baseline and week 12.ResultsParticipants were 75 % female and 62.5 % black. The baseline mean (± SD) age, body weight, and BMI z‐score were 14.3 ± 1.5 y, 96.0 ± 21.9 kg, and 2.21 ± 0.48, respectively. The lower protein group reduced BMI z‐score compared to the higher protein group (0.18 ± 0.16 vs. 0.05 ± 0.09; p<0.05). No other group differences were found but fullness tended to increase in the higher protein group (0.5 ± 20.5 vs. 14.9 ± 15.2; p=0.08). Participants lost 3.1 ± 2.0 kg vs. 1.5 ± 4.2 kg body weight and 2.8 ± 2.4 % vs. 3.0 ± 5.2 % body fat in the lower vs. higher protein groups, respectively. The lower protein group change from baseline BMI z‐score, body weight, and body fat were reduced (p≤0.002) but the higher protein group change from baseline values were not different from baseline. Exploratory analyses, with the protein groups combined, indicated that overweight adolescents reduced BMI z‐score 0.38 ± 0.12 compared to 0.07 ± 0.08 in the obese subgroup (p<0.01).ConclusionsParticipants in the higher protein group tended to increase fullness, but this did not translate to greater weight loss. Higher dietary protein intake should not be recommended for weight loss in group based interventions in this study population. An adolescent intervention based on the USDA MyPlate guidelines is efficacious for weight loss in adolescents.Support or Funding InformationNIH U54 GM104940 and NIH P30 DK072476
A Father's Response to Having a Child who is Overweight/Obese
Authors: Battisti Francis Louis , Battisti Helen E. 
Published: November 2023

Study ObjectiveThe objective of this qualitative study was to develop a theory to understand a father's response to having a child who is overweight or obese. This study was pursued for four reasons: 1) The literature is rich with studies that explore the influences of the mother/child interaction as it relates to weight. 2) Studies exploring the influences of the parent/child perspective, as they relate to weight of the child, tend to focus on maternal influences, while largely ignoring the paternal impact. 3) The limited number of father/child interaction studies suggests that researchers see this relationship as insignificant. 4) Studies that do explore the father's influence tend to look only at paternal genetic factors which contribute to the child's weight.Statement of MethodsA Grounded Theory research design was utilized to develop a theory to understand a father's response to having a child who is overweight or obese. The fathers (n=12) were recruited from a family medical practice in Upstate New York. Using a two‐component approach, demographic information was obtained, followed by a semi‐structured individual interview to understand each father's response. All were the biological fathers and married, with two in the process of divorce. The mean age (n=10) was 42.6 years (two fathers refused to report their age). Eleven fathers were Caucasian and one was Hispanic/Latino. The mean age of the children, all of whom were >85% for weight (n=13, 77%M) was 9.6 years. One father had two children who met the research criteria.Summary of ResultsThe interviews revealed the complex, multi‐dimensional nature of identifying aspects of the father's response to his child's overweight or obese status. From the interviews, six themes evolved: 1) Fathers worry about their child being overweight or obese related to psychological and physical health. 2) Fathers experience confusion as to the cause of their child being overweight. 3) Fathers minimize their impact on their child's weight and eating behaviors. 4) Fathers become overwhelmed and non‐functional when attempting to address their child's overweight or obesity. 5) Fathers defer responsibility for their child's weight to others when they don't know how to help their child manage weight. 6) Fathers engage with their child's weight issues when they can cognitively and/or emotionally understand what the child is feeling. The Theory of Interactive Factors That Lead to a Father's Response (TIF) was developed.Conclusion StatementLimited research regarding the father's influence on a child's weight has been conducted. With fathers making up an estimated 16% of stay‐at‐home parents, researchers are becoming increasingly interested in the role that fathers play. The TIF provides a framework that increases the understanding of motivational factors of fathers for affective and cognitive engagement.Support or Funding InformationNone
Ethnic Differences in Cumulative Exposure to Food Insecurity and Risk of Childhood Asthma
Authors: Mangini Lauren D , Dong Yongquan , Hayward Mark D , Forman Michele R 
Published: November 2023

Background & ObjectivesPrevalence rates of asthma have steadily risen in the U.S. and are higher in non‐Hispanic black (NHB) than in non‐Hispanic white (NHW) or Hispanic children. Likewise, NHBs are at higher risk for food insecurity than the other 2 ethnic groups. Little is known about the relationship between cumulative exposure to household food insecurity and childhood asthma. The objective was to determine the relationship between exposure to food insecurity and asthma in NHW, NHB and Hispanic school‐aged children.MethodsData from 4 waves of the Early Childhood Longitudinal Study‐Kindergarten cohort (ECLS‐K) were analyzed beginning in kindergarten through 8th grade (N=6,031). Food insecurity was measured with the 18‐item USDA module and at each wave of data collection, an episode is defined as household food insecurity during the prior year. Ever‐diagnosis of asthma and sociodemographic characteristics were parent‐reported; anthropometric data were collected in person. Multivariate logistic regression models were stratified by race to test the association between cumulative exposure to food insecurity and ever being diagnosed with asthma, controlling for covariates.ResultsAmong NHWs, odds of asthma were highest in children in households that had two episodes of food insecurity and were ever poor (OR 2.80, 95% CI 2.69–2.92). Among NHBs, one episode of food insecurity and ever being poor were associated with the highest odds of asthma (OR 2.05, 95% CI 1.97–2.14). Among Hispanics, one episode of food insecurity alone was associated with the highest odds of asthma (OR 1.63, 95% CI 1.58–1.69). Contrasting results appeared by ethnic group for parental depression, with odds for NHWs (OR 1.74, 95% CI 1.72–1.75) higher than Hispanics (OR 1.06, 95% CI 1.05–1.08) and NHBs (OR 0.98, 95% CI 0.96–0.99). Results were adjusted for child sex, birth weight, health insurance status, overweight or obesity, and maternal nativity and education.ConclusionIn 2014, 19% of U.S. households with children experienced food insecurity, which we have previously demonstrated is associated with asthma. These results demonstrate that asthma is associated with strong ethnic differences in life course exposure to food insecurity and poverty. Thus, recent pediatric healthcare policy urging screening for food insecurity at pediatric visits may potentially reduce interethnic health disparities in asthma outcomes.Support or Funding InformationMs. Mangini and Dr. Forman are supported by the David Bruton, Jr. Professorship funds.
Food Insecurity Status and Mortality in Ontario, Canada
Authors: Gundersen Craig , Tarasuk Valerie , Cheng Joyce , de Oliveira Claire , Kurdyak Paul , Dachner Naomi 
Published: November 2023

Multiple negative health outcomes are linked to household food insecurity in Canada and the US. What has not been examined, though, is whether food insecurity is associated with higher risks of mortality. We examined the relationship between individuals’ food security status over a 12‐ month period and their mortality status (a) at any point since the survey and (b) within four years of the survey. We used data for 67,033 Ontario adults from the Canadian Community Health Survey linked with administrative health care data. Among individuals 18 to 64, 2.3% of food secure individuals had died at some point after the survey while over twice as many severely food insecure individuals (6.1%) had died. Among individuals over the age of 65, the figures are 24.5% and 33.1%. Even after adjusting for age, sex, education, homeownership, household composition, and neighborhood income quintile, when we look at all adults, mortality rates at any time after the survey are 95.3% higher for severely food insecure, 40.4% higher for moderately food insecure, and 26.8% higher for marginally food insecure adults versus food secure adults; when mortality within four years is considered, that rate is 83.6% higher for severely food insecure and 49.4% higher for moderately food insecure adults. Our results suggest that household food security status is a robust predictor of mortality, further indicating the importance of pursuing policies to reduce food insecurity.Support or Funding InformationFunded by the Canadian Institutes of Health Research (FRN 115208).