bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermuscular adipose tissue according to obese phenotype in Korean obese individuals
Authors: Yim Jung‐Eun , Kim Young‐Seol 
Published: November 2023

IntroductionAdipose tissue (AT) and its distribution are major risk factor for metabolic diseases. The purpose of this study was to investigate body composition measured by whole body maJgnetic resonance imaging (MRI) and to elucidate the association of metabolically healthy but obese (MHO) and metabolically abnormally obese (MAO) with their cardiometabolic risks in Korean obese individuals.MethodsSubjects were classified as metabolically abnormal obese (MAO) at‐risk with ≥ 3 cardiometabolic abnormalities by the NCEP criteria. The following criteria were used to determine metabolically healthy obese (MHO) status. Body composition was measured by bioimpedance, dual X‐ray absorptiometry (DXA) and whole body MRI methods. MRI images were analyzed by SLICEOMATIC image analysis software. Resting energy expenditure (REE) and respiratory quotient (RQ) were evaluated by indirect calories methods. Fasting blood levels of glucose, insulin, lipids, alanine aminotransferase (ALT), aspartate aminotrasferase(AST), leptin, visfatin, and adiponectin were determined.ResultsMHO men (n=5, BMI 27.3) and MAO men (n=8, BMI 27.9) were significantly different in trunk subcutaneous adipose tissue (SAT) and lower leg total adipose tissue (p<0.05), but were not different in visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT). MHO (n=7, BMI 25.9) women and MAO (n=8, BMI 27.9) women were significantly different in arm SAT and leg IMAT (p<0.05), but were net different in VAT. The average amounts of IMAT were 72.8g and 40.8g in MAO men and women, respectively. REE and RQ were not different in MAO and MHO. The levels of leptin were significantly correlated with trunk SAT and leg SAT.ConclusionsThese results suggested that the amount of IMAT was much in Korean men than women and significantly different in Korean MAO and MHO women.Support or Funding InformationThis research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education, Science and Technology(NRF‐2013R1A1A3010917)
Birth weight, early life weight gain and age at menarche: a systematic review of longitudinal studies
Authors: Juul Filippa , Chang Virginia , Brar Preneet , Parekh Niyati 
Published: November 2023

Background and objectiveAdiposity in pre‐ and postnatal life may influence age of menarche. Evidence linking BMI and menarche is primarily cross‐sectional, failing to address temporality, for which the role of adiposity in early life remains unclear. The objective of the current study was therefore to systematically review longitudinal studies evaluating the associations between birth weight and infant/childhood weight status/weight gain in relation to menarcheal age.MethodsFive databases were systematically searched: PubMed, EMBASE, Web of Science, Global Health (Ovid) and CINAHL. Selected studies were limited to English‐language articles, sample n≥200, presenting multi‐variable analyses. Fifteen original research articles reporting risk estimates for birth weight (n=4), infant/childhood weight gain/weight status (n=4), or both (n=7), in relation to menarcheal age were included. Information on cohort name, study location, years of study, study design, sample size, outcome, exposure, contrast group, risk estimates and confounders was extracted.ResultsAge at menarche was significantly associated with birth weight in eight of eleven studies. Greater BMI or weight gain over time and greater childhood weight was significantly associated with earlier menarche in seven of seven and five of six studies, respectively.ConclusionsTaken together, studies suggested that lower birth weight and higher body weight and weight gain in infancy and childhood may increase the risk of early menarche. This review suggests that the pre‐ and post‐natal period may be an opportune time for weight control interventions to prevent early menarche, and its subsequent consequences.Support or Funding InformationThis study was unfunded.
Increased Transcription of the Seryl‐tRNA Synthetase (SARS) Gene in Response to Amino Acid Limitation is Mediated by an Intronic C/EBP‐ATF Response Element (CARE) that Functions as an Distal Enhancer
Authors: Shan Jixiu , Sharkey Jason , Tsang Sylvia , Kilberg Michael S 
Published: November 2023

Amino acid (AA) limitation activates transcription from 16 of the 20 genes encoding cytoplasmic‐localized aminoacyl‐tRNA synthetase (ARS) genes via action of activating transcription factor 4 (ATF4) binding at C/EBP‐ATF‐Response‐Element (CARE) enhancers. Most of the activated genes have a functional CARE near the transcription start site (TSS), but for some the CARE is located downstream within the first intron. For all ARS genes, regardless of the CARE location, there is constitutive association of RNA polymerase II (Pol II) and the general transcription machinery (GTM) near the TSS. For those genes with a downstream CARE, during AA limitation there is enhanced recruitment of ATF4, Pol II, and the GTM to the CARE, not the TSS region. The AAR‐induced expression of ARS genes results from modulation of transcription elongation. Using the seryl‐tRNA synthetase (SARS) gene as a model, the goal of the present research was to further characterize the mechanism by which an intronic CARE enhancer, about 1 kb downstream of the TSS, functions to increase transcription in response to AA limitation. Using CRISPR‐CAS9 technology and HepG2 hepatoma cells, the SARS CARE was deleted and then the wild type and SARS‐CARE−/− cells were subjected to AA limitation. Analysis at both the promoter and the CARE regions of the SARS gene revealed significant changes in association of the GTM, transcription elongation factors, and enhancer binding proteins, in a CARE‐specific manner. Likewise, the absence of the CARE caused changes in localized histone modification within the SARS genomic locus. Collectively, the results indicate that intronic CARE enhancers, such as those contained within the ARS gene family, modulate transcription from the corresponding promoter through changes in histone modification and recruitment of specific factors that control elongation.Support or Funding Informationthis work was supported by a grant to MSK from The National Cancer Institute, CA203565.
Interaction Between the Ratio of Polyunsaturated Fat and Saturated Fat Intake and Peroxisome Proliferator‐Activated Receptor‐γ Coactivator 1‐α (PPARGC1A) rs4235308 Polymorphism in Relation to the Risk of Type 2 Diabetes in Cuban American Population
Authors: Xu Ling , Cheema Amanpreet , Zarini Gustavo G. , Li Tan , Huffman Fatma G. 
Published: November 2023

BackgroundResults from multiline studies suggested that oxidative stress might be the underlying cause of the development of insulin resistance, β‐cell dysfunction, impaired glucose tolerance and type 2 diabetes (T2D). The importance of the peroxisome proliferator‐activated receptor‐gamma, coactivator 1 (PPARGC1A) in mitochondrial biogenesis and regulation of oxidative stress has been extensively investigated. Association of PPARGC1A variants with T2D has been confirmed in several studies. Differences in environmental factors, particularly dietary factors influencing oxidative stress balance, may mask some genetic association. We hypothesized that the association of a common variant (SNP rs4235308) in PPARGC1A gene may be altered by the ratio of polyunsaturated to saturated fats (P/S fat ratio) in the diet.Subjects/MethodsWe genotyped rs4235308 polymorphism in the PPARGC1A gene from 315 Cuban Americans (164 without T2D/151 with T2D) using ABI TaqMan assays. Logistic regression method was used to assess the association between rs4235308 genotypes in an additive model and the risk of T2D. Interaction was tested by including the product of genotype*P/S fat ratio in the model.ResultsThere was no significance between rs4235308 polymorphism and the risk of T2D when we didn't include the P/S fat ratio in the model. After including the P/S fat ratio and the interaction term in the model, a strong interaction was evident between P/S fat ratio and rs4235308 polymorphism for the risk of T2D (P=0.010) after adjusting for body mass index (BMI), age, gender, physical activity and calorie intake. SNP rs4235308 (OR=0.57, P=0.027) showed a protective association with T2D for the subgroup who has a lower P/S fat ratio (P/S fat ratio < median (0.456)) while there were no significant results when the same analysis was conducted in the subgroup that had a higher P/S fat ratio (P/S fat ratio ≥ median). In addition, we found that the P/S fat ratio was negatively associated with serum HDL‐cholesterol level in T2D patients (P=0.008) after adjustment of BMI, age, gender, physical activity and calorie intake. Further analysis on this association stratified by genotyping status (C allele carrier vs. non‐carrier) showed that the negative association between serum HDL‐cholesterol and the P/S fat ratio in patients with T2D was only significant in non‐carrier (P=0.021).ConclusionThe common PPARGC1A rs4235308 variant was associated with decreased risk of T2D in Cuban American when dietary P/S fat ratio was low. Dietary factors need to be taken into consideration when investigating genetic associations with T2D within populations.Support or Funding InformationFunding for this research was provided through an NIH/NIDDK sponsored grant # SC1DK083060
Correlation of mRNA Levels with CpG Methylation Status of Genes Regulated by Fatty Acids in Differentiated Adipocytes
Authors: Li Yi , Cheng Elliott , Bower Brittney 
Published: November 2023

Adipose and muscle tissues are significantly affected in obesity and type 2 diabetes. In order to study the involvement of epigenetic modifications in mediating gene expression induced by diets, 3T3‐L1 preadipocytes were cultured in media containing saturated fatty acids to mimic hyperlipidemia conditions, which occur during the development of obesity and type 2 diabetes. DNA methylation sequencing was used to identify the methylated regions from the DNA samples isolated from the differentiated 3T3‐L1 adipocytes treated with saturated and polyunsaturated fatty acids. In combination with the pool of previously identified genes that mRNA levels were regulated by fatty acids, we have found correlation between some of the highly methylated regions with the genes that were regulated by fatty acids. We are currently individually validating methylation status of these highly methylated genes including RASA2, MEF2C, and GRP78. We are also studying the signaling pathways mediating methylation of these genes.Support or Funding InformationThis research is supported by grant SC3GM116737 from the NIGMS of the NIH to Y. Li.
EFFECTS OF PROTEIN SUPPLEMENTATION ON FRAILTY AND SARCOPENIA IN PRE‐FRAIL AND FRAIL ELDERLY: STUDY PROTOCAL FOR A DOSE‐RESPONSE, DOUBLE‐BLIND, RANDOMIZED PLACEBO‐CONTROLLED TRAIL
Authors: Park Yongsoon , Kwon Soo‐Jung 
Published: November 2023

With a rapidly aging population, frailty defined as geriatric syndrome that increases the risk of falls, disability, hospitalization and mortality, is a major health concern. Previous studies suggest that protein supplementation is an effective dietary strategy to decrease frailty by positively influence aspects of sarcopenia in elderly. However, adequate amount of protein intake for preventing or delaying development of frailty is still a controversial issue. The aim of this study was to investigate the dose‐dependent effect of protein supplementation on muscle mass, frailty status and physical performance in pre‐frail and frail malnourished elderly.This study is a double‐blind randomized controlled trial with concealed allocation and intention‐to‐treat analysis. This study was approved by the Institutional Review Board of Hanyang University (HYI‐15–228). A total of 120 participants aged from 70 to 85 who meet one or more of the Cardiovascular Health Study (CHS) frailty criteria (weight loss, exhaustion, low physical activity, slowness and low handgrip strength) with risk of malnutrition (Mini Nutritional Assessment (MNA) ≤23.5). Participants are excluded if they have comorbidities such as kidney and liver failure and are unable to communicate. During 12 weeks, eligible participants will be randomly assigned to either control, 1.2 g/kg body weight or 1.5 g/kg body weight protein group taking iso‐caloric supplementation. Primary outcomes is appendicular muscle mass, and secondary outcomes include CHS frailty score, Korean Longitudinal Study on Health and Aging (KLoSHA) frailty criteria (Short Physical Performance Battery, Korean Activity of Daily Living, Korean Instrumental Activity of Daily Living, the Korean Mini‐Mental State Examination, serum albumin), timed up and go, falling history, admission history, hsCRP, C‐peptide, insulin‐like growth factor 1 and MNA. Safety measurement, compliance and adverse effect are also measured.TRIAL REGISTRATION NUMBER: Clinical Research Information Service (CRIS, http://cris.nih.go.kr): KCT0001923.Support or Funding InformationThis study was supported by a Korean Health Industry Development Institute grand funded by the Korean Government (HI15C3207).
Dietary Pattern Associated with Frailty: Results from Nutrition and Health Survey in Taiwan
Authors: Pan Wen‐Harn , Lo Yen‐Li 
Published: November 2023

ObjectivesTo identify dietary patterns and to explore their associations with frailty.DesignAnalyses were conducted with data from the Nutrition and Health Survey in Taiwan (NAHSIT), a representative nationwide survey.SettingParticipants were recruited from NAHSIT between 2013 and 2015.ParticipantsIndividuals aged 65 years and older (N=954).MeasurementsDietary intake was evaluated using a 79‐item food‐frequency questionnaire. Frailty phenotype was determined using the modified Fried criteria. Using data from NAHSIT 2013 (n=274), we applied reduce rank regression to find dietary pattern which maximized the variation explained for multiple parameters associated with frailty, including grip strength, lean mass, hemoglobin concentration, 36‐item Short‐Form, and Brief Symptom Rating Scale‐5. Logistic regression models were used to estimate the association between frailty and dietary pattern using data from NAHSIT 2014–2015 (n=680).ResultsConsumption frequency of vegetable, tea, whole grains, shell fish, nuts and seeds, snacks, fish, and poultry were positively associated, but that of sweetened beverage was inversely associated with the frailty parameter. Prevalence of frailty and pre‐frailty was 4.7% and 45.9%, respectively in the NAHSIT 2014–2015 survey where we first incorporated Fried questionnaire. Dietary pattern score tertiles were inversely associated with frailty risk (odds ratio=1, 0.64, 0.10; p for trend=0.03).ConclusionA dietary pattern featured with more “phytonutrient‐rich plant foods, tea, low‐saturated fat containing protein‐rich foods, n‐3 rich deep‐sea fish, discretionary calories from between‐meal snack; but less sweeten beverage” was associated with lower risk of frailty. This information can be considered in designing dietary intervention for frail elders.Support or Funding InformationThis study was supported from the intramural funds from the Health Promotion Administration, Ministry of Health and Welfare (MOHW103‐HPA‐H‐114‐124710) and the Department of Health (DOH102‐HP‐1703) in Taiwan.
Alaskan berry treatments maintain C. elegans motility and sarcomere integrity with age
Authors: Touray Farimang , Maulik Malabika , Scerbak Courtney , Vayndorf Elena , Ito Abel Bult , Taylor Barbara 
Published: November 2023

Maintaining health with age is a major health concern due to loss of muscle mass, locomotion and increased likelihood of developing neurodegenerative disease associated with increased chronological age. This project aims to study the impact of consuming Arctic‐adapted Alaskan berries has on the maintenance of health with age. We tested the hypothesis that bog blueberry (Vaccinium uliginosum) and low bush cranberry (Vaccinium vitis‐idaea) treatments improve various markers of health in the model organism Caenorhabditis elegans. Individually, blueberry and low bush cranberry treatments significantly increase mean lifespan and result in the maintenance of motility with age. However, concurrent blueberry and cranberry treatment results in no significant change in lifespan and no improvement in motility over control, suggesting that the molecular mechanisms behind the lifespan extension of the two berries are antagonistic. For muscle integrity, only Alaskan blueberry had a significant improvement in muscle integrity when compared to the control. We also investigated the role of Alaskan berry treatments on the onset of paralysis in C. elegans models of Alzheimer's and Parkinson's disease. This study establishes the role of Alaskan botanicals as possible therapeutic agents for aging and neurodegenerative disorders, and encourages further exploration of active ingredients within the extracts.Support or Funding InformationProject funded by Biomedical Learning and Student Training (BLaST)
The Effects of Age on the Gut and Brain: Insights into the Gut‐Brain Axis
Authors: Hoffman Jared , Bakshi Vikas , Parikh Ishita , Guo Janet , Armstrong Rachel , Green Stefan , Lin Ai‐Ling 
Published: November 2023

Age is the top risk factor for the development of numerous diseases including neurological disorders such as dementia. Indeed, this may be due to the increased inflammation exhibited in the aging process. Interestingly, an altered gut microbiota has also been linked to increasing one's risk for the development of inflammation and neurological disorders. We hypothesize that with age, this inflammatory response originates in the gut and reaches the brain, disrupting the gut‐brain axis, and increasing one's risk of disease. Our objective was to examine the effects of the aging process on the gut‐brain axis in Young and Old mice and how this can alter brain function. Specifically, our multi‐faceted approach included magnetic resonance imaging, P‐gp transport via brain capillary isolation, mTOR staining, biochemical assyays, behavior testing, brain metabolomics assessment, and 16S sequencing of the gut microbiome. Our preliminary results found variations in the diversity and taxa of the gut microbiome and an increased inflammatory response in the brain with age. Collectively, we conclude the aging process may indeed alter the gut microbiome and increase inflammation in the brain but more research needs to be conducted to further elucidate the mechanisms of the gut‐brain axis.Support or Funding InformationThe study was supported by NIA K01AG040164 to Dr. Ai‐Ling Lin
Potential Skin Anti‐Aging Effects of Korean Medicinal Plant Extracts
Authors: Averilla Janice Nullan , Kim Jeung Eun , Ju Sung Hee , Oh Jisun , Kim Jong‐Sang 
Published: November 2023

The development of a variety of human diseases is related to aging. During the aging process, a normal homeostatic condition of biological systems including free radicals, antioxidants and biomolecules, becomes disrupted, promoting the accumulation of oxidants that cause deterioration of vital cellular functions. Thus, alternative methods in delaying the signs of aging, such as functional food supplementation, have emerged in the past few decades. In previous research studies, antioxidants have been reported to stimulate the expression of the genes that regulate essential antioxidant signaling pathways. As part of the global continuous effort to inhibit the rate of skin aging, we screened various Korean traditional medicinal plant extracts by examining the effect on the cellular defense key transcription factors, particularly nuclear factor erythroid 2 (NF‐E2)‐related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), and heme oxygenase 1 (HO‐1). Interestingly, two of the plant extracts screened, Inula japonica Thunberg (dogyeong) and Carpeslum abrotanoides Linne (hakseul), resulted in enhanced antioxidant gene expression in mouse hepatoma Hepa1c1c7 and human keratinocyte HaCaT cells as measured by Western blot and were found to provide strong beneficial effect against skin aging. Additionally, we evaluated the effect of the plant extracts on transcriptional activity of Nrf2 using a cell line stably transfected with antioxidant response element (ARE) and reporter luciferase gene. We also demonstrated that the non‐toxic administration of dogyeong and hakseul had notable skin anti‐aging effect in animal model, thereby warranting further clinical efficacy study.Support or Funding InformationThis study was funded by BK21 Plus Program
Decreased consumption of specific macronutrients promotes metabolic health and longevity
Authors: Cummings Nicole Elise , Radcliff Abigail , Brodbeck Allison , Konon Elizabeth , Wu Jessica , Sherman Dawn , Williams Elizabeth , Apelo Sebastian Arriola , Barnes Macy , Hacker Timothy , Lamming Dudley 
Published: November 2023

Calorie restriction (CR) is the nutritional ‘gold standard’ in lifespan extension, improving metabolic health in many metabolic organisms. This intervention is extremely difficult to sustain, especially in a population struggling with both obesity and readily available food sources. While CR limits the intake of all macronutrients, it's unclear what macronutrient drives these benefits. An attractive alternative to restricting all calories is to limit only certain macronutrients, changing the ratio of macronutrient intake. A low protein, high carbohydrate diet can increase lifespan and improve metabolic health in both rodents and humans. However, the specific amino acid composition of protein intake may have more of an impact on metabolism and aging than researchers and physicians previously thought.Our lab has previously determined that a diet restricted in branched chain amino acids (BCAAs; leucine, isoleucine, and valine) improves glycemic control and metabolic health in young, wild‐type mice. In addition, we have determined that reduced consumption of BCAAs does not induce the production of fibroblast growth factor 21 (FGF21), a hormone produced in fasting and protein restriciton, but does result in specific inhibition of the mechanistic Target of Rapamycin Complex 1 (mTORC1). We have since expanded our research to explore the effects of BCAA restriction in aged and metabolically disadvantaged mice.We find that Low BCAA diets rapidly reverse diet induced obesity, improving glucoregulatory control and inducing weight loss. When BCAAs or total protein are restricted in a progeroid mouse, we promote longevity and rescue some aspects of cardiac function. BCAA restriction improves weight and glycemic control of aged, wild‐type mice. Our results suggest that a reduction in dietary BCAAs promotes metabolic health and longevity, and may represent a highly translatable option to treat age‐related disease.Support or Funding InformationThe Lamming lab is supported by a K99/R00 Pathway to Independence Award to D.W.L. from the National Institute of Health/National Institute on Aging (AG041765), a New Investigator Program Award from the Wisconsin Partnership Program, and an Innovator Award from the Progeria Research Foundation, as well as startup funds from the UW‐Madison School of Medicine and Public Health and the UW‐Madison Department of Medicine. N.E.C. is supported in part by a training grant from the UW Institute on Aging (NIA T32 AG000213). This work was supported using facilities and resources from the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States Government.