bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomics and Lipidomics Analysis of the NIA CALERIE Trial
Authors: Kristal Bruce S , Gathungu Rose M , Bird Susan S , Marur Vasant R , Sniatynski Matthew J , Sheldon Diane P ,   CALERIE Clinical Trial Consortium
Published: November 2023

Calorie Restriction (CR) is the most potent, robust, and reproducible known means of extending longevity and decreasing morbidity in a vast range of animal species short of primates. Despite 80 years of research, the relevance of this observation for humans remains unknown. Relevance is supported by the established link between obesity and morbidity in humans, and the health status of individuals voluntarily participating in a caloric restricted lifestyle. Other potential linkages are being directly studied in the NIA/NIH‐sponsored CALERIE (Comprehensive Assessment of Long‐term Effects of Reducing Intake of Energy) clinical trial. CALERIE enrolled 238 individuals and collected blood samples at 6 time points over 24 months. We previously examined metabolomics (via HPLC separation with coulometric electrode array‐based detection) and lipidomics (via high resolution LC‐MS‐based lipidomics) effects of the CALERIE intervention and compared these data to those previously obtained in studies of ad libitum fed and calorically restricted FBFN1 rats (males/females, different ages and extents and durations of CR). The results were, surprisingly, nearly completely negative. Retrospective Post‐Hoc analyses identified three potential reasons for these negative findings. First the original trial and our analyses intended to strictly follow trial design (i.e., intention to treat analysis), were powered for a 25% drop in caloric intake – a larger and more consistent goal than was obtained. Second, many individuals on the low calorie diet intervention lost weight in year one but gained in year two – a shift in caloric balance for which our analyses initially were, again in accordance with an intent‐to‐treat design, unprepared to compensate. Third, and most important, we determined that exposure of the forearm to high temperatures prior to some phlebotomy (termed “hot‐box”) time points — which was essential to assess one listed secondary clinical outcome of the trial — destroyed self‐similarity for our measures, rendering the baseline sample unusable for our standard normalization and control methods. Correcting for this revealed some of the expected biological/biochemical differences and provided a potentially interesting signal related to altered stress response in relationship to some aspect of caloric intake, obesity, and/or energy expenditure, consistent with the cognate literature in animal models of normal and delayed aging. We will discuss the results, the implication for metabolomics and lipidomics studies, and initial, promising re‐analysis of these CALERIE data.Support or Funding InformationNIA/NIH
The Replication Kinase Cdc7 Marks Histones to Regulate Biosynthesis Genes
Authors: Grant Patrick 
Published: November 2023

Post‐translational histone modifications (PTMs) play important roles in regulating various DNA‐templated cellular functions including transcription, DNA damage repair, DNA replication and telomeric silencing. Histone H3 Threonine 45 phosphorylation (H3T45ph) is a modification that is enriched during S‐phase of the cell cycle in Saccharomyces cerevisiae and is carried out by the kinase Cdc7‐Dbf4 (DDK) in vivo and in vitro. To understand the function of this mark we identified the genomic H3T45ph locations by performing chromatin immunoprecipitation followed by high throughput sequencing (ChIP‐Seq) of wild‐type budding yeast cell chromatin. Remarkably, this PTM is observed not only at origins of DNA replication, but is also uniquely distributed on the promoters of highly transcribed RNA polymerase I, II and III‐regulated genes dedicated to protein synthesis and glycolysis. Here we show that H3T45 phosphorylation, mediated by Cdc7‐Dbf4, is required for polymerase recruitment and full expression of ribosome protein (RP) and tRNA genes as well as for the regulation of cohesin loading. Collectively, we identify an unexpected gene regulatory function for the DNA‐replication kinase Cdc7‐Dbf4 and identify a novel histone modification regulating the protein biosynthesis gene machinery.Support or Funding InformationThis work is supported by NIH award R01 GM111911.
Mechanism of Neuroprotectin D1 Action after Hypoxic‐Ischemic Injury in Neonatal Mice
Authors: Zirpoli Hylde , Sosunov Sergey A. , Niatsetskaya Zoya , Mayurasakorn Korapat , Manual Denny Joseph Kollareth , Norris Paul C. , Reilly Ian R. , Serhan Charles N. , Ten Vadim S. , Deckelbaum Richard J. 
Published: November 2023

Neonatal hypoxic‐ischemic (HI) brain injury remains a major contributor to neurological disorders in children. We recently reported that acute administration of triglyceride emulsions of docosahexaenoic acid (tri‐DHA) after HI injury, showed marked neuroprotection in neonatal mice decreasing infarct volume by 50%. Post‐HI tri‐DHA injection preserved Ca2+ buffering capacity and markedly decreased reactive oxygen species (ROS) production by mitochondria. We questioned whether DHA‐derived specialized pro‐resolving mediator (SPM) profiles change in ischemic brains of tri‐DHA treated mice relative to untreated mice, and if SPMs directly activate the same mechanisms of neuroprotection as tri‐DHA. After 2h reperfusion we detected a 50% increase in neuroprotectin D1 (NPD1) levels in brains of tri‐DHA treated mice compared to the control group. Tri‐DHA administration also increased brain levels of total D‐ and E‐series resolvins, and LXB4, by 5.8 and 2.5‐fold respectively. Based on these observations, we examined whether NPD1, a potent bioactive mediator derived from DHA, could lead to neuroprotection immediately after HI brain injury. We found that acute intraperitoneal administration of 20ng NPD1 after HI injury reduced infarct volume by 55% compared to saline treated mice (control group). Short‐term neurofunctional outcomes were assessed at 24h after HI. Treatment with NPD1 significantly improved righting and negative geotaxis reflex performances compared to control littermates. Mitochondria from ischemic brains of NPD1 treated mice had similar Ca2+ buffering capacity compared to naïve mice, while mitochondria from the ischemic brains of control treated mice significantly reduced Ca2+ buffering capacity by 40% compared to naïve mice (p<0.05).A number of studies by other groups have reported that dietary n‐3 fatty acids may prevent or reverse impairments in mitochondria content or function. Our findings show that acute injection of a DHA derived mediator, namely NPD1, directly provides neuroprotection after HI and this is associated, in part, by preserving mitochondrial functions.
Providers' Perceptions of Child Feeding and Activity Recommendations Related to Early Childhood Obesity Prevention
Authors: Heller Rebecca , Chiero Jesse , Trout Nancy , Mobley Amy R 
Published: November 2023

Early childhood obesity prevention from birth to 24 months of age (B‐24) is a growing public health concern. However, the child feeding and activity information provided to parents is limited and inconsistent which may contribute to confusion regarding obesity prevention for their children. This is partially due to the lack of uniform dietary guidelines to promote healthy weight in children from B‐24. The objective of this qualitative study was to identify common resources and recommendations used by health and education providers and any misconceptions or barriers faced when educating parents on early childhood feeding and activity practices. One‐on‐one interviews were conducted with health and education providers (n=14) working with families of young children from a variety of demographic and socioeconomic backgrounds. Interviews were audio‐taped, transcribed verbatim, and analyzed using the classic analysis approach. The study results revealed several important themes including how only healthcare providers, but not education providers, working with children B‐24 directly address childhood obesity prevention with parents. Providers reported confusion from parents about when to transition to solid foods and how much or what to feed their child as commonly perceived barriers to optimal child feeding. Parental misconceptions about feeding were often due to cultural, family and media influences, as well as lack of personal knowledge or experience. Screen time and physical activity of children B‐24 were much less of a concern to providers. Sources of child feeding information used by providers to educate parents were derived mainly from online sites and often from non‐evidence based sources. Providers indicated a need for consistent feeding and childhood obesity prevention messaging and free, non‐commercial sources of online information to provide to parents.Support or Funding InformationThe Child Health and Development Institute of Connecticut, Inc.
Food Addiction and Dietary Intake in Morbidly Obese Females Before and After Vertical Sleeve Gastrectomy
Authors: Kim Ashley , Moore Carolyn , Sherman Vadim , Tariq Nabil , Maziarz Mindy 
Published: November 2023

Bariatric surgery can be a successful treatment option for morbid obesity when dietary, exercise, and pharmacotherapy interventions fail. However, food addiction (FA) is a condition that can hinder the perceived value of food reward resulting in overconsumption of highly palatable food. The presence of FA not only contributes to the development of obesity but may also lessen weight loss success that occurs from bariatric surgery. The aim of this study was to examine dietary intake and identify the prevalence of FA in obese women before and three months following vertical sleeve gastrectomy (VSG). Obese females [body mass index (BMI) ≥ 35] undergoing VSG were recruited from a bariatric surgical practice at Houston Methodist Hospital in Houston, Texas. The Yale Food Addiction Scale (YFAS) questionnaire and 24‐hour dietary recall were administered by a Registered Dietitian Nutritionist during the pre‐surgery and three‐month post‐surgery clinic appointments. FA was identified based on results from the YFAS questionnaire, which assessed seven diagnostic symptoms for FA and clinical impairment. Mean energy and nutrient (carbohydrate, fat, protein, fiber, and added sugar) intake were analyzed by the Nutrition Data System for Research program. Fifteen morbidly obese females (mean age of 46.5 ± 3.1 years) were enrolled in the study and 60% (n = 9) reported having FA. Prior to VSG, the mean body weight of females with FA and without FA was 134.4 ± 13.5 kg versus 135.4 ± 10.2 kg, respectively. Likewise, the females with FA had a mean BMI of 50.9 ± 3.9 kg/m2 compared to 49.5 ± 2.7 kg/m2 in the group without FA. Mean body weight, BMI, energy or nutrient intake did not differ between groups before or three months following VSG. However, the females with FA resolution post‐VSG (n = 7; 53.3%) had significant reductions in weight (−13.1%, P = 0.010), BMI (−10.9%; P = 0.037), energy (−43.4%; P = 0.011), fat (−51.9%; P = 0.013), carbohydrate (−42.7%; P = 0.014), and fiber (−45.9%; P= 0.022). The females without FA before and after VSG (n = 6; 40%) had a −7.4% reduction in weight (P = 0.049) and −11.5% reduction in BMI (P = 0.026) without significant changes in nutrient intake over time. Three months post‐VSG the prevalence of FA decreased by −72.1% with only 16.7% (n = 2) reporting FA. In conclusion, body weight and BMI are similar in morbidly obese females with and without FA. VSG resulted in significant reductions in energy, fat, carbohydrate, and fiber intake that coincided with the resolution of FA post‐surgery. VSG is an effective surgical procedure that decreases nutrient intake and assists in the resolution of FA in morbidly obese females.Support or Funding InformationFaculty Research Enhancement Program from the Office of Research and Sponsored Programs at Texas Woman's University
The Impact of Avocado Fruit on Postprandial Satiety: an Acute Dose Response Study
Authors: Huang Yancui , Park Eunyoung , Xiao Di , Edirisinghe Indika , Burton‐Freeman Britt M 
Published: November 2023

Avocado fruit contains a unique combination of monounsaturated fat and dietary fibers. Previous studies have tested the effects of fat or fiber on satiety/appetite control; however data are limited on the interaction of fat and fiber to enhance satiety. The aim of the present study was to characterize the effect of avocados, a fruit naturally high in healthy fat and dietary fiber, on subjective and biological indicators of satiety. Thirty‐one adults who were overweight or obese (body mass index 29.0 ± 2.4 kg/m2, age 37.9 ± 10.3 y, n = 16 female and n = 15 male) participated in this 3‐arm, single‐blinded, cross‐over clinical trial. Participants were provided a low fat high carbohydrate breakfast control meal (CON) or two energy‐matched meals containing either half an avocado (HA, 68 g) or a whole avocado (WA, 136 g) on 3 different occasions at least one week apart. Blood samples were collected at baseline (0 h) and 0.5, 1, 2, 3, 4, and 6 h after treatment to assess changes in glucagon‐like peptide‐17‐36 (GLP‐1), peptide YY3‐36 (PYY) and total ghrelin. Visual analog scales (VAS) were used to measure changes in subjective satiety (hunger, fullness, desire to eat, and prospective consumption) and mood variables during the same 6 h time frame. Area under the curve analysis indicated the WA meal increased GLP‐1 by 17% and PYY by 21% compared to the CON meal, p < 0.05, whereas ghrelin was suppressed 25% more after the CON meal compared to WA meal, p < 0.05. Assessment of motivation to eat and mood variables indicated a significant reduction in prospective consumption after the WA and HA meals compared to CON meal, p ≤ 0.05 and increased fullness after WA meal compared to HA (P<0.05), but not compared to CON (p=0.11). The study results indicate that increasing the fat and fiber content of a breakfast meal with avocados compared to an iso‐energetic low fat meal increased feelings of fullness and reduced the amount of food subjects wanted to eat over 6 h. These data are consistent with an elevation in two known satiety peptides (GLP‐1 and PYY) and suggest that avocados may have an important role in helping individuals manage the amount they want to eat between meals and possibly at the next meal.Support or Funding InformationSupported by Hass Avocado Board, Irvine, CA
Soluble Dietary Fiber in Obesity‐Associated Inflammation and Oxidative Stress in African American Women
Authors: Nance Sierra A. , Duncan A'ja V. , Gwathmey TanYa M. , Hairston Kristen G. 
Published: November 2023

Obesity is a growing epidemic afflicting 1 in every 3 adults in the U.S. and characterized by an excessive accumulation of subcutaneous and visceral adipose tissue (VAT). VAT induces inflammation through the secretion of inflammatory cytokines and consequently promotes oxidative stress, increasing the risk for cardiovascular disease (CVD). Recent studies suggest that dietary fiber induces weight loss in obese subjects; however, there is little evidence regarding the effects of fiber on inflammation and oxidative stress. Therefore, the present study set out to determine if increased soluble dietary fiber intake reduced obesity‐associated inflammation and oxidative stress in a cohort of premenopausal, non‐diabetic, obese African American women. Subjects were randomized to receive 24 grams/day of Benefiber® (n=7) or placebo (n=9) over a 12‐week period. Blood samples were collected at baseline and 12‐week follow‐up visits. Changes in VAT were determined by computed tomography. At the end of the trial, a reduction in VAT was observed for both the fiber supplemented and placebo groups (−17.56 ± 5.03 vs −12.58 ± 4.29); however, the percent change in serum levels for the pro‐inflammatory cytokine IL‐8 were significantly lower in the fiber‐treated group compared to the placebo group (−22.4 ± 13.67 vs 10.34 ± 6.47; p=0.03). There was no effect of fiber supplementation on the percent change in serum CRP expression (−87.49 ± 40.88 vs −94.54 ± 38.91); the percent change in serum levels of oxidative stress marker, 8OHdG (4.75 ± 3.98 vs −0.87 ± 3.34); or percent change in serum cortisol levels (10.53 + 12.83 vs −6.80 + 8.38). However, significant positive correlations were observed between VAT and CRP (R2=0.19; p=0.04); VAT and 8OHdG (R2=0.20; p=0.03); and cortisol and 8OHdG (R2=0.32; p=0.01). In summary, increased soluble dietary fiber intake reduced IL‐8 levels, while elevated levels of VAT were associated with increased levels of CRP and 8OHdG, suggesting that soluble dietary fiber mitigates obesity‐associated inflammation as a consequence of fat loss, accompanied by reduced levels of oxidative stress. In conclusion, increasing intake of soluble dietary fiber may be beneficial in reducing the risk for CVD, especially in high‐risk populations, such as African American women.Support or Funding InformationHypertension & Vascular Research Pilot Funding (PI: Hairston)
Parabacteroides distasonis attenuates colonic inflammation and prevents tumor formation in azoxymethane‐treated high‐fat diet‐fed mice
Authors: Koh Gar Yee , Kane Anne V. , Lee Kyongbum , Xu Qiaobing , Wu Xian , Mason Joel B. , Crott Jimmy W. 
Published: November 2023

Obesity is a major risk factor for colorectal cancer (CRC) and inflammation is thought to constitute one of the underlying mechanisms. We previously observed a depletion of Parabacteroides distasonis (PD) in the stool of tumor‐bearing mice that was inversely related to the abundance of the pro‐inflammatory cytokine IL‐1β in the colon. Here, we aimed to determine whether the administration of PD can suppress obesity‐driven colonic inflammation and tumorigenesis in mice. Six‐week old male A/J mice were randomly assigned to receive one of the 3 diets: 1) low fat diet with 10% calories from fat (LF), 2) high fat diet with 60% calories from fat (HF), and 3) HF+0.04% w/w of freeze‐dried P.distasonis (HF+PD). After 1 week, mice were given 4 weekly injections of the colon carcinogen azoxymethane and were maintained on their respective diet for 20 weeks after the final injection. Histologically‐confirmed colonic tumors were observed in 0% (0 of 19), 25% (5 of 20) and 0% (0 of 20) of LF, HF and HF+PD mice, respectively (Fisher's exact test = 0.0049). Compared to HF mice, HF+PD mice tended to have reduced colonic TNFα concentrations (30% lower; P = 0.08). Activations of both MyD88‐dependent innate immune signaling and Akt signaling have been implicated in inflammation and tumorigenesis. Compared to HF mice, colonic MyD88 and phosphorylated Akt protein expression were reduced by 39% (P < 0.01) and 47% (P = 0.03), respectively, in HF+PD mice. Our results indicate, for the first time, that administration of PD can prevent HF diet‐driven tumorigenesis and attenuate colonic inflammation in azoxymethane‐treated mice. Associated with PD administration was a reduction in pAkt and Myd88, suggesting that PD, to a certain extent, blunts inflammatory signaling. Further work is required to fully elucidate the mechanism and confirm our findings in alternate mouse models of CRC.Support or Funding InformationThis project is funded by Tufts Institute for Innovations
A pilot study assessing whether the consumption of a protein‐rich breakfast improves appetite control, eating behavior, and sleep quality compared to skipping breakfast in healthy young professionals
Authors: Gwin Jess A. , Leidy Heather J. 
Published: November 2023

BackgroundPrevious research has documented the detrimental effects of breakfast skipping on daily appetite control, satiety, and eating behaviors and improvements in these outcomes following the daily consumption of a high‐protein (HP) breakfast in overweight/obese adolescents. While relatively unexplored, observational studies have also illustrated other health‐related detriments with breakfast skipping, including poor sleep quality. Thus, we sought to extend the current evidence to healthy young professionals and include assessments of sleep quality.PurposeTo examine the effects of consuming a HP breakfast vs. breakfast skipping on daily appetite control, food intake, and sleep quality in healthy young professionals.MethodsThirteen adults (age: 23.5 ± 0.9y; BMI: 23.6 ± 0.6 kg/m2) completed the following randomized cross‐over design. The participants consumed a HP breakfast (350kcal; 30g Protein, 35g Carbohydrate, 10g Fat) or skipped breakfast (SKIP) for 7 days/pattern. On day 7 of each pattern, a tightly controlled 8 h clinical testing day was completed consisting of repeated assessments of perceived hunger, fullness, desire to eat, and prospective food consumption (PFC). Food intake and food choice were assessed with an ad libitum packout. Sleep quality was assessed via daily actigraphy and daily sleep diaries.ResultsDaily hunger, desire to eat, and prospective food consumption were decreased (all p < 0.05) following the HP breakfast vs. SKIP. Daily fullness tended to increase (p = 0.067) following the HP breakfast vs. SKIP. The consumption of the HP breakfast tended to decrease ad libitum food intake (1831 ± 284 kcal) vs. SKIP (2251 ± 365 kcal, p = 0.087), through the reduction in ad libitum carbohydrate and fat intake. Regarding the sleep outcomes, although the consumption of a HP breakfast led to less total sleep time (TST) (actigraphy: 381±13 min) vs. SKIP (actigraphy: 417±14min, p < 0.05), no differences in sleep efficiency (TST/Sleep Period) were detected. Further, perceived sleep quality and sleep onset tended to improve following the consumption of the HP breakfast vs. SKIP (p = 0.060–0.077).ConclusionsCollectively, the daily consumption of a HP breakfast tended to improve appetite control, reduced food intake, and may support improvements in some aspects of sleep health in healthy professionals.Support or Funding InformationInternal Grant