bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying fatty acid synthesis using heavy water: Enabling back‐to‐back studies
Authors: Previs Stephen , Herath Kithsiri , Nawrocki Andrea , Singh Sheo , Kang Ling , Erion Mark , Kelley David 
Published: November 2023

Studies aimed at modulating the contribution of de novo lipogenesis (DNL) to lipid homeostasis are of interest. For example, there appears to be an increased contribution of DNL in cases of dyslipidemia and adipose accretion suggesting that the inhibition of fatty acid synthesis may affect clinical phenotypes. Unfortunately, it is unclear whether inhibition of one specific step in the lipogenic pathway is more important than another. Heavy water (D2O) is generally considered to be a reliable isotopic tracer for quantifying DNL. In contrast to other tracers, D2O yields a homogeneous and quantifiable precursor labeling. However, a drawback of using D2O centers on the relatively long half‐life of water implying that one must wait a substantial time before performing repeat studies in the same subjects; this can create a bottleneck in the development and evaluation of novel therapeutics for inhibiting DNL especially in cases where one aims to use subjects as their own controls. We previously demonstrated the ability to perform back‐to‐back studies of glucose and cholesterol flux by administering multiple doses of D2O and therein circumvent an extensive washout time; presumably these “tricks” can help minimize resources and decrease the turnaround time when testing hypotheses. Herein we now demonstrate the ability to perform back‐to‐back studies of DNL using D2O. However, we have identified special circumstances that limit some aspects of the data analysis, i.e. it is possible to obtain what appear to be negative values for DNL. Using a rodent model we have identified the physiological mechanism that explains the data. We show that one can use D2O to test inhibitors of DNL by performing back‐to‐back studies in higher species (i.e. treat non‐human primates with platensimycin, an inhibitor of fatty acid synthase).Support or Funding InformationAll authors were employed by Merck while this work was being done.
Exogenous Oxidation of Lipids Reduces The Deleterious Effects of A High Fat Diet Composed of These Lipids in A Swine Model of Familial Hypercholesterolemia and Spontaneous Atherosclerosis
Authors: Arowolo Folagbayi , Meudt Jennifer J. , Cabelka Colin , Schomberg Dominic T. , Chesmore Nathan J. , López Ana Cecilia Escobar , Trace Sam T. , Reichert Jamie L. , Crenshaw Thomas D. , Richards Mark P. , Shanmuganayagam Dhanansayan 
Published: November 2023

High‐fat diets elevate the risk of atherosclerotic cardiovascular disease (CVD), especially in individuals susceptible to dyslipidemia. Dietary fats consumed in westernized countries contain increasingly higher proportions of lipid oxidation byproducts, such as lipid hydroperoxides (LPOs), because of changes in agricultural, food processing, and cooking practices over the years. Although the formation of LPOs within the body is recognized as a central driver of the atherosclerotic process, it is unclear what impact exogenous (dietary) LPOs have in this context. We postulated that LPOs in the diet would not pose the same risk because of existing mechanisms for mitigating their absorption at the gastrointestinal level. Thus, we examined whether the conversion of a portion of lipids into LPOs by deep frying would reduce the atherogenicity of a high‐fat diet composed of such lipids in a novel swine model of spontaneous atherosclerosis.We placed four‐month old swine with familial hypercholesterolemia on the following isocaloric dietary regimens for four months: (1) [Control, N=6] low‐fat swine diet (~9% calories from fat); (2) [HF–LPOs, N=5] high‐fat diet (~44% calories from fat) containing negligible amounts of LPOs; (3) [HF+LPOs, N=5] high‐fat diet (~44% calories from fat) containing LPOs generated by heating of oil under an established protocol. The diets delivered equal amounts of micronutrients. Body weight (BW) measurements and serum samples were obtained at baseline and monthly during the study. At the end of the study period, the animals were euthanized and tissue harvested for gross and histological analysis of atherogenesis. Compared to the Control group, the HF–LPOs group showed a 58.5±20.4% increase in total serum cholesterol (TSC), while the HF+LPOs group only showed a 38.5±9.1% increase in TSC. Compared to HF–LPOs group, HF+LPOs showed a 20±11% lower BW gain over the course of the study; there was no notable difference in food intake. Compared to the Control group, the HF–LPOs group showed a 45.6±44.2% higher degree of atherogenesis in the aorta, while the HF+LPOs group only showed a 21.5±38.5% higher atherogenesis. The findings, taken together, suggest that oxidation of a portion of fats in the diet reduces the deleterious effects of the fat by potentially reducing the amount that is absorbed.Support or Funding InformationThe research was supported by the Biomedical & Genomic Research Group Discretionary Fund, University of Wisconsin‐Madison.
Sex differences of body fat distribution in mexican adolescents 10–14 years old with Type 2 Diabetes Mellitus risk factors
Authors: Soto‐Piña Alexandra , Esquivel‐Roque Aurora , Flores‐Reséndiz Constantino , Fernández‐Gaxiola Ana Cecilia , Tlatempa‐Sotelo Patricia 
Published: November 2023

Overweight and obesity are risk factors for developing type 2 Diabetes Mellitus (T2DM). While they are associated with insulin resistance, it is unclear how sex and body fat percentage contribute to the appearance of T2DM risk factors in adolescents. There are few methods to analyze body composition at early life stages, among them the Slaughter equation has proved to be suitable and accurate to obtain the body fat percentage in adolescents. The aim of this study was to determine body fat percentage in adolescents between 10 to 14 years old and to identify adolescents at risk of developing T2DM. The sample consisted of 66 adolescents aged 10 to 14 years who met one or more of the following criteria: fasting glucose ≥100 mg/dL, presence of acanthosis nigricans, family history of T2DM, BMI ≥percentile 95th and hypertension (≥percentile 90). Triceps, subscapular and calf skin folds were measured and the percentage of body fat was obtained. The 11.0% of the population presented low weight, 37.0% normal weight, 25.4% overweight and 28.0% obesity. Moreover, 31.0% of girls had overweight and 25.0% obesity, while the 41.20% of the boys had normal weight and 32.4% obesity. Also, 32.0% of boys and 50.0% of girls had a high body fat percentage. Girls had higher rate of android like hip waist (78.1%). The results indicate that female adolescents have higher body fat percentage mostly in the abdominal region unlike male adolescents and may be more prone to develop T2DM risk factors.Support or Funding InformationBridge Grant UAEMEX‐UNTHSC
Differences in body composition according to gender in schoolchildren in Arandas, Mexico
Authors: Romero‐Velarde Enrique , Caro‐Sabido Erika Alejandra , Vasquez‐Garibay Edgar Manuel , Larrosa‐Haro Alfredo 
Published: November 2023

ObjectiveIdentify differences in body composition according to gender in schoolchildren population of Arandas, and associated factors.MethodsA crossover design in 268 children from 57 to 155 months old. Random multistage sampling was performed in schools in town. Sociodemographic data were collected; anthropometric measurements of the study subjects (weight, height, arm circumference, waist circumference and skin folds) and their mothers (weight, height, waist circumference) were performed. Body composition was assessed by bioelectrical impedance. Energy and macronutrients consumption was evaluated with two dietary surveys by 24‐hour recall. Descriptive statistics were performed; body composition characteristics were compared between boys and girls. The project was approved by the Ethics and Research Committee at the University of Guadalajara.ResultsMean age 96.9 ± 27.2 months, 53.7% male. The values of all parameters of adiposity were higher in boys, but the differences were not statistically significant. The values of waist circumference (p <0.05) energy consumption (p= 0.02) and carbohydrates consumption (p= 0.003) were higher in boys. Mothers of boys had a higher BMI, body fat percentage, waist circumference and prevalence of obesity, than mothers of girls. The maternal BMI was positively correlated with BMI of their children; with a higher correlation with BMI of boys (r=0.42, p <0.001 vs r=0.27, p <0.01).ConclusionsAdiposity was higher in boys vs girls, although the difference was not significant. Genetic (maternal adiposity), epigenetic, and environmental variables (increased energy and carbohydrates consumption) could explain the higher prevalence of obesity in boys in Mexico.
Anthropometric Measurements Differ among Overweight and Obese Adults of Varying Socioeconomic Status but no Differences in Fruit and Vegetable Intake
Authors: Rhee Yeong , Honrath Kerrie , Wagner Meredith G. 
Published: November 2023

Individuals of lower socioeconomic status (SES) tend to have higher rates of obesity and eat poorer quality diets than their counterparts of higher SES. The study was conducted to determine if fruit and vegetable (F/V) intake and anthropometric measurements differ among overweight and obese adults of varying SES. The study was a cross‐sectional design that included 38 adults from the Midwestern United States with a body mass index (BMI) of >25 kg/m2. The study looked at education level, personal income, and household income separately to assess SES. Weight, height, body fat percentage, and waist circumference were measured and BMI was calculated. Intake of F/V was measured by averaging daily intakes from three‐day food records. The results showed that F/V intake did not vary significantly among those of varying SES but BMI and body fat percentage did. Individuals with higher education levels as well as higher personal incomes had a significantly lower BMI and body fat percentage. Also, those with higher household incomes had a significantly lower body fat percentage. Overweight and obesity appear to be more prevalent among those of lower SES, which is why nutrition intervention is important for this population; however, focus should be on barriers to eating higher quality diets other than affordability such as taste, availability, and motivation to make changes.Support or Funding InformationThe research was funded by grants from the Department of Health, Nutrition, and Exercise Science and College of Human Development and Education at North Dakota State University.
DHA Supplementation Alters Cofilin1/pVASP‐S239 Expression, Sub‐cellular, Localization, and Suppresses Migration and Proliferation in Lung Cancer Cells
Authors: Ali Mehboob , Heyob Kathryn M , Rogers Lynette K 
Published: November 2023

Cancer cells exhibit higher migration rates and greater cell viability facilitated by actin binding protein (ABP)‐mediated cytoskeletal remodeling and secondary messengers. APB like vasodilator stimulated phosphoprotein (VASP) and cofilin1 regulate actin remodeling. cGMP mediated VASP phosphorylation at serine 239 (pVASP‐S239) via PKG and cofilin1 are associated with actin stabilization. Docosahexaenoic acid (DHA) has been shown inhibit cancer cell metastatic phenotype. We hypothesize that DHA enhances pVASP‐S239 and its association with cofilin1 to attenuate actin dynamics‐mediated cancer cell migration and survival.Non‐cancer (MLE12) and cancer (A549) cells were treated with DHA for 6h and 24h. pVASP‐S239 and cofilin1 expression were analyzed by western blot and total F‐actin content and VASP/cofilin expression and localization were assessed by immunofluoresence. Cell migration was estimated by wound assay and transwell apparatus. Ki67 and caspase 3 expressions measured by flow cytometry. Protein expression of pVASP‐S239 and cofilin1 increased with DHA supplementation compared to control. F‐actin content, cell migration, and proliferation were decreased with DHA supplementation in cancer cells but not in non‐cancer cells. With stimulation, cellular distribution of cofilin1 and pVASP‐S239 were observed in the perinuclear region while DHA supplementation caused the expression to moved towards cellular edges.In conclusion, DHA specifically inhibits cancer cell migration and proliferation and this effect correlates with ABP expression and subcellular distribution patterns. DHA supplementation suppresses cellular changes related to metastatic potential in cancer cells and could provide therapeutic potential against cancer cell metastasis.Support or Funding InformationThis work was supported by the National Institutes of Health, NCCIH/ODS (LKR R01AT006880).
Antioxidative activity of (3R,3R’) and (3S,3S’) astaxanthin in Caenorhabditis elegans
Authors: Liu Xiaojuan , Luo Qingxin , Cao Yong , Liu Xin , Xiao Hang 
Published: November 2023

As a potent antioxidant in human diet, astaxanthin (AST) may play important roles in alleviating oxidative stress‐driven adverse physiological effects. In this study, we determined the anti‐oxidative and anti‐aging effects of different stereoisomers of AST in Caenorhabditis elegans (C. elegans). Three stereoisomers of AST investigated herein included 3S,3′S (S) AST, 3R,3′R (R) AST and a mixture (S: meso: R=1:2:1) (M) AST. Under normal culture environment, treatment with S, R and M AST extended median lifespan of C. elegans by 27.61%, 25.25% and 22.69%, respectively. Under the peroxidation conditions, all three types of AST significantly enhanced survival rate of C. elegans. The accumulation levels of ROS were reduced by 40.12%, 30.05% and 22.04% by S, R and M AST, respectively (P<0.05). Compared with R and M AST, S significantly enhanced the expression levels of SOD‐3. The results of RNA‐Seq demonstrated that AST protected C. elegans from oxidative damage potentially by modulating the insulin/insulin‐(IIS) pathway and the oxidordeuctase system. It is noteworthy that the different stereoisomers of AST showed different effects on the expression levels of various genes related with oxidative stress. This study provided important information on the in vivo antioxidative effects of AST stereoisomers.Support or Funding InformationNational Natural Science Foundation of China (31401481)
Lutein‐supplemented formula enhances lutein accumulation in brain and other tissues in infant rhesus macaques
Authors: Jeon Sookyoung , Ranard Katherine M. , Neuringer Martha , Johnson Emily E. , Kuchan Matthew , Johnson Elizabeth J. , Erdman John W. 
Published: November 2023

Lutein, a yellow xanthophyll, is well known for its critical role in eye health, and several recent studies also showed associations of lutein intake with improved cognitive function in adults. In addition, it has been suggested that lutein's presence as the most abundant carotenoid in brain may contribute to neural development. However, there is limited data on the effect of lutein bioaccumulation in early life. The purpose of this pilot study was to investigate if a lutein‐supplemented infant formula can increase lutein deposition in brain regions and other tissues using a nonhuman primate model. Infant rhesus macaques (1–3 months old) were fed either a control formula containing a basal level of lutein (10 nmol/L) (n=2) or a formula with a higher level of lutein (100 nmol/L) (n=2) to mimic the breast milk composition from mothers consuming a healthy vegetable‐rich diet. Serum carotenoids were measured monthly, and retina, brain, and other tissues were collected after 4 months of feeding. The levels of carotenoids in serum and tissues were analyzed by high‐performance liquid chromatography. Final serum lutein level in the supplemented group was 5 times higher than in the unsupplemented group (104 nmol/L and 21 nmol/L, respectively). Lutein accumulated differentially across brain areas. Occipital cortex exhibited the highest lutein level among brain areas regardless of the formula type, and was 3‐fold higher in the supplemented group (64 pmol/g versus 21 pmol/g). The other brain areas, including prefrontal and superior temporal cortex, striatum, hippocampus and cerebellum, all showed increased lutein concentrations in supplemented group; indeed, in the unsupplemented group, lutein was undetectable in prefrontal and superior temporal cortex and cerebellum. Lutein was two times higher in mesenteric and thigh subcutaneous adipose tissues, three times higher in abdominal adipose tissue and six times higher in brown adipose tissue in the supplemented group compared with the unsupplemented group. In addition, higher lutein deposition was found in liver, lung, kidney, heart, and other tissues. In conclusion, infant rhesus macaques showed enhanced lutein levels in serum, brain and other tissues in response to formula lutein supplementation, and lutein was preferentially deposited in the occipital cortex. This pilot study demonstrates that increased early exposure to dietary lutein substantially enhances lutein tissue deposition.Support or Funding InformationFunding provided by Abbott Nutrition through the Center for Nutrition, Learning and Memory, University of Illinois, Urbana‐Champaign, and NIH grant P51OD011092.
Retinoic Acid Pretreatment Promotes Vitamin A Accumulation in the Lung of Neonatal Rats
Authors: Li Yaqi , Urbanek Joanna K , Green Michael H , Tan Libo , Ross A. Catharine 
Published: November 2023

Previous studies conducted in our laboratory have shown that a combination of vitamin A (VA) and retinoic acid (RA), known as VARA, increased total retinoid concentration in plasma, liver and lung in neonatal rats. Later studies have further shown that supplementation with VA alone may stimulate the uptake of VA into the liver, resulting in a significantly higher liver total retinol concentration. Here, in order to distinguish the effects of VA and RA, we examined the effect of RA pretreatment, preceding a single‐dose supplementation with VA, on the metabolism and kinetics of total retinoid in plasma and lung tissue of neonatal rats. Sprague‐Dawley female and male rats were mated, and the females were housed with continuous access to food and water and were fed a VA‐marginal diet (0.35 mg retinol equivalents/kg diet). On postnatal day 2 and 3, each pup received an oral dose of either RA (0.625μg /g body weight) or canola oil as the control treatment. Then, on postnatal day 4, all pups received an oral dose of VA (6 μg retinyl palmitate/g body weight) containing 2 μCi of [3H]‐retinol as tracer. Pups (n = 4–6/treatment/time point) were euthanized at 12 time points from 25 min to 30 h after dose administration and the following tissues were collected: plasma, liver, lung, spleen, kidney, heart, stomach, intestine, brain, skin, brown adipose tissue and carcass. Tissue retinoid concentration was determined by ultra‐performance liquid chromatography (UPLC), and the tissue tracer level was determined by liquid scintillation counting. Results showed that, in plasma, retinyl ester was first detected at the 30 min time point, then rapidly increased and peaked at approximately 2 h after dosing and gradually declined afterwards, whereas the retinol level increased slowly and peaked between 4.5–6 h and remained nearly steady until 30 h after dosing. Nevertheless, no significant difference was observed in the plasma 3H tracer response between the two treatment groups. Total retinol in the lungs of the RA‐pretreated group, integrated over the 30‐h study, was ~3 times higher compared to the oil‐pretreated group. In addition, our tracer data showed that a greater proportion of the newly ingested VA was present in the lung of the RA‐pretreated group compared to the oil‐pretreated group. In conclusion, our findings indicate that RA supplementation may modify lung uptake of VA even though RA was given prior to the VA dose.Support or Funding InformationNIH grant HD‐066982
Selective Delivery of Xanthophylls to Human Retinal Pigment Epithelial Cells (ARPE‐19) via Human Lipoproteins
Authors: Thomas Sara , Harrison Earl H 
Published: November 2023

Age‐related macular degeneration (AMD) is an incurable disease affecting older adults in the United States that leads to blindness. Xanthophylls are dietary carotenoids of interest because they selectively accumulate in the macula of the eye and are thought to provide protection against AMD. To reach the macula, xanthophylls and other nutrients such as β‐carotene must cross the retinal pigment epithelium (RPE) through the choroid from the human blood. Xanthophylls associate mostly with HDL (high density lipoprotein) in human serum while β‐carotene associates mostly with LDL (low density lipoprotein). HDL binds to cells via a scavenger receptor class B1 (SRB1)‐dependent mechanism while LDL binds via the LDL receptor (LDLR). Using an in‐vitro, human cell model (ARPE‐19), we studied the mechanisms of xanthophyll (lutein and zeaxanthin) uptake into the RPE cell by evaluating kinetics of cell uptake when carotenoids were delivered in LDL or HDL. For lutein and β‐carotene, LDL delivery resulted in the highest rate and extent of uptake. In contrast, HDL was more effective in delivering zeaxanthin resulting in the highest rate and extent of uptake of the 3 compounds. The preferential uptake of zeaxanthin from HDL and lutein from LDL may be facilitated by SRB1 and LDLR, respectively. Adding increasing amounts of unenriched LDL to lutein‐enriched LDL and unenriched HDL to zeaxanthin‐enriched HDL, decreased xanthophyll uptake in both instances. Competition for access to SRB1 or LDLR between the xanthophyll‐enriched lipoprotein and the unenriched lipoprotein may occur as the unenriched lipoprotein concentration increases. Because carotenoid uptake is lipoprotein‐dependent, we evaluated whether competition may occur between β‐carotene, lutein, or zeaxanthin for cell uptake. Using whole serum to deliver lutein or zeaxanthin in the presence of increasing amounts of β‐carotene, lutein, or zeaxanthin, we found that β‐carotene decreased lutein uptake. Zeaxanthin uptake was unaffected by either lutein or β‐carotene. Using serum amyloid albumin (SAA), an acute phase inflammatory protein known to block HDL binding to SRB1, and BLT‐1, a chemical inhibitor of HDL uptake by SRB1, we evaluated zeaxanthin uptake by HDL in ARPE‐19 cells. Compared to the control treatment, zeaxanthin delivery via HDL was reduced by 49% and 52% by SAA and BLT, respectively. Our results suggest a selective HDL‐mediated uptake of zeaxanthin via SRB1 and potentially a LDL‐mediated uptake mechanism for lutein via LDLR. Overall, our results may partly explain selective uptake of xanthophylls into the RPE.Support or Funding InformationNIH Grant R01HL48679 and R01DK44498