bluuebunny/crossref_metadata_2025 huggingface dataset:
The Substrate‐Protein and Protein‐Protein Interactions of Fatty Acid and Polyketide Mega‐Synthases
Authors: Tsai Shiou‐Chuan (Sheryl)
Published: November 2023

Polyketide derived natural products are a large and diverse class of secondary metabolites used in the pharmaceutical and agricultural industry. These include antibiotics, immunosuppressant's, chemotherapeutics and insecticides. Examples of valuable polyketide compounds include tetracycline (antibiotic), lovastatin (cholesterol‐lowering) and rapamycin (immunosuppressant). The multi‐domain enzyme complex that is responsible for the biosynthesis of polyketides is known as the polyketide synthase (PKS). Similar to the PKS, the fatty acid synthase (FAS) is a multi–domain enzyme complex that utilizes acyl‐CoA's as building blocks to generate linear poly‐beta keto intermediates that can be subsequently processed via reduction, dehydration or other acyl‐chain modifying reactions. Both FAS and PKS utilize the acyl carrier protein (ACP) that functions as the transporter protein that is covalently tethered to the nascent polyketide intermediate. Polyketide and fatty acid production require three basic biosynthetic steps: (1) Polyketide elongation, (2) polyketide modification and (3) polyketide release from the ACP. How the ACP interacts with enzyme domains from all of these steps is not well understood. Unlike FAS, PKS utilize a much more diverse polyketide starter units, modification reactions that give rise to the rich chemical diversity of polyketide natural products. One of these important modifications includes the regio‐specific cyclization and aromatization of linear poly‐b‐keto intermediates. How the different PKS promote different cyclization patterns is not well understood. Lastly, how polyketide ACP‐tethered intermediates are released from the PKS machinery needs further investigation. An elucidation of the mechanism by which these bioactive polyketides are cyclized and/or released while being tethered to the ACP would be highly significant in the prediction, identification and engineered biosynthesis of new polyketides. Herein we present the structural enzymology of the effect of protein‐substrate and protein‐protein interactions on the product outcomes for these mega‐synthases.
Functional Lipidomics: From Lipid Timelines To Regulation Of Metabolic Networks
Authors: Ejsing Christer S.
Published: November 2023

Lipids play essential roles in membrane structure and dynamics, energy homeostasis, and signal transduction. The lipidome of eukaryotic cells comprises several hundred molecular lipid species produced by a metabolic network that interconnects and coordinates the metabolism of fatty acids, glycerophospholipids, glycerolipids, sphingolipids and sterol lipids. One of the grand challenges in cell physiology is to understand how cells regulate the activities of all lipid metabolic pathways simultaneously not only to maintain lipid homeostasis but also to remodel cellular processes and architecture. To delineate the regulatory landscape of lipid metabolism, we deploy systems biology approaches to reproducibly, comprehensively and quantitatively monitor both lipid molecules and the proteins that operate the lipid metabolic network. These approaches include high throughput lipidomics workflows capitalizing on nanoelectrospray ionization and high‐resolution Orbitrap mass spectrometry combined with quantitative shotgun proteomics for time‐resolved quantitative analysis of lipidome and proteome dynamics. The power of this platform is exemplified by our recent discoveries that: (i) activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis, (ii) down‐regulation of de novo sterol synthesis machinery prompts differential turnover of lipid droplet‐associated triacylglycerols and sterol esters, and (iii) sphingolipid metabolism is regulated in a previously unrecognized growth stage‐specific manner. The application of this proteolipidomics technology serves as a new experimental paradigm for understanding, at unprecedented temporal resolution, how lipid metabolism is regulated and coordinated with the remodeling of cellular architecture and processes.
Protandim Treatment Causes Reversible Nuclear Translocation of Nrf‐2 and Activation of the Antioxidant Response Element
Authors: Chevreau Nathalie
Published: November 2023

Protandim® is a natural product supplement which activates antioxidant protective pathways through induction of the Nrf‐2 transcription factor. We set out to elucidate the mechanism and kinetics by which this occurs through a series of cell‐based assays. AREc32 cells, harboring the luciferase reporter gene under the control of a tandem repeated antioxidant response element (ARE), were treated with Protandim. A time dependent evaluation of Protandim treatment showed an increase in ARE‐controlled reporter gene expression starting at 12 hours, and peaking at approximately 24 hours post‐treatment. Furthermore, a concentration dependent curve of Protandim treatment suggested that 48 μg/mL provided maximal induction with no change in cell viability. To gain a better understanding of the kinetics associated with Nrf‐2 subcellular localization, studies utilizing immunofluorescence and ELISA protein quantification were performed in normal intestinal epithelial cells. The cells were initially treated with 24 μg/mL of Protandim and then washed off at 2 hours to mimic contact time that Protandim would have with intestinal cells when taken orally. It was observed that the Nrf‐2 protein was translocated to the nucleus within 1 hour of treatment, and reached a maximum level at approximately 10 hours. This inducible translocation was reversible: from 12 hours to 24 hours post‐treatment, Nrf‐2 signal gradually returned to baseline pre‐treatment levels. When Protandim was re‐applied at 12 hours and again washed off 2 hours later, Nrf‐2 protein did not continue to accumulate in the nucleus, but was maintained at a steady augmented (but sub‐peak) level throughout treatment. To determine whether Nrf‐2 nuclear localization would stimulate the growth of cancer cells, we treated HCT‐116 and CaCo‐2 colon cancer cells with varying doses of Protandim. At no point in time or dose was the activation of Nrf‐2 by Protandim associated with increased tumor cell viability. Viability curves showed that Protandim was cytotoxic at moderate doses. These data support the inducible mechanism of action of Protandim, and provide justification for daily or twice‐daily supplementation.

Support or Funding Information

Wasatch Scientific Services conducted all experiments
M‐A‐T (Mucuna, Ashwagandha and Tribulus) Enhances Testosterone and Reduces Oxidative Stress: In Vivo Model
Authors: Juturu Vijaya , Sahin Kazim , Akdemir Fatih , Orhan Cemal , Tuzcu Mehmet , Turk Gaffari , Sahin Nurhan , Yilmaz Ismet
Published: November 2023

Background

Mucuna, Ashwagandha and Tribulus (M‐A‐T) are a traditional herbal medicine used to enhance sexual health and functional activities. This study investigates the possible role of M‐A‐T at two different doses (30 mg M‐A‐T and 60 mg M‐A‐T) on sex hormones (testosterone, follicle‐stimulating hormone and luteinizing hormone), oxidative stress (serum and testis MDA), sperm motility, count and rate and gene proteins with the intent to show its usefulness in improving sexual health.

MATERIALS AND METHODS

In this experimental study, we randomly divided 36 rats into four groups: I. Negative control, II. Positive control‐treated, III. M‐A‐T 1 (10 mg Mucuna(M), 10 mg Ashwagandha (A) and 10 mg Tribulus (T)/kg BW) IV. M‐A‐T 2‐treated (20 mg Mucuna, 20 mg Ashwagandha and 20 mg Tribulus/kg BW) was administrated 8 weeks. At the end of the treatment period, the sex hormones [testosterone (TT), follicle‐stimulating hormone (FSH) and luteinizing hormone (LH)], oxidative stress (serum and testis MDA), sperm motility, count and rate and gene proteins (NFkB, Nrf2 and HO1) of all rats’ sera were determined by radioimmunoassay and Elisa kits. The data obtained were statistically analyzed using the ANOVA, followed by post‐hoc Tukey test. P<0.05 was considered significant.

RESULTS

The M‐A‐T 1 and M‐A‐T 2 group had a significantly increased TT, FSH and LH level than the control group (p<0.05). There was no significant difference between the treated M‐A‐T 1 and 2 groups. The treated control group had a significant decrease in serum and testis MDA levels, decrease in NFkB and an increase in Nrf2 and HO1 was observed in both M‐A‐T treated groups than controls. M‐A‐T 1 and 2 significantly improved sperm motility, count and rate. No significant changes in liver and kidney functions (ALT, AST, creatine, ALP and urea) in any of the treated groups.

CONCLUSION

Oral consumption of M‐A‐T could improve sexual health and function by enhancing sex hormones and reducing oxidative stress.

Support or Funding Information

OmniActive Health Technologies Inc.
FTO Genotype, Dietary Protein Intake and Body Weight in a Population of Young Adults
Authors: Jamnik Joseph , Merritt David , El‐Sohemy Ahmed
Published: November 2023

Background

Variation in the fat mass and obesity‐associated gene (FTO) has been shown to be associated with susceptibility to obesity. There may be a link between patterns of dietary intake, variation in FTO and obesity, but the relationship remains unclear. Previous studies have shown that dietary protein might modify the association between FTO genotype and body weight and composition.

Objective

The objective was to determine whether protein intake modifies the association between FTO variant rs1558902 and BMI/waist circumference.

Methods

Participants (n=1,491) were from the Toronto Nutrigenomics and Health Study, a cross sectional examination of young adults. Lifestyle, genetic, anthropometric and biochemical data were collected and diet was assessed using a Toronto‐modified Willett food frequency questionnaire. General linear models stratified by ethnicity and adjusted for age, sex and total energy intake were used to examine the association between rs1558902 and measures of body weight, and whether protein intake modified any observed associations.

Results

East Asians with protein intake below the median (<17% total energy intake) who were homozygous for the risk allele (A) of rs1558902 had significantly higher BMI (AA= 25.0 kg/m2, AT/TT=21.5kg/m2; p< 0.0001) and waist circumference (AA=78.9 cm, AT/TT=70.6cm; p=0.0006) compared to carriers of the T allele. These associations were absent in the high protein intake group (>17% total energy intake) and there was a significant gene‐diet interaction for both BMI (p=0.01) and waist circumference (p=0.007). No significant interactions were observed among the Caucasian or South Asian groups.

Conclusion

These findings suggest that dietary protein intake might modify the effect of FTO variants on measures of body weight in certain populations.

Support or Funding Information

Research support from the Advanced Foods and Materials Network.
Spatial reorganization of Proopiomelanocortin (POMC)‐expressing Neurons in the Arcuate Nucleus of POMC‐EGFP Mice Resistant or Prone to Obesity
Authors: Tomé Daniel , Soto Marion , Chaumontet Catherine , Guillaumin Mathilde , Benoit Simon , Fromentin Gilles , Andrey Philippe , Burguet Jasmine , Darcel Nicolas
Published: November 2023

Overweight and obesity have been linked to an increased consumption of energy from palatable dense foods enriched in fats, sugars and sucrose‐sweetened beverages. However, susceptibility towards weight gain under an obesogenic diet varies between individuals. Mice have been characterized as obesity‐prone (OP) and obesity‐resistant (OR) in relation with their capacity to gain weight when fed an obesogenic high‐fat high‐sucrose (HFHS) diet. In the brain, the arcuate nucleus (ARC) of the hypothalamus is the main area involved in the control of energy homeostasis. The ARC hosts two key neuronal populations, one of those expressing proopiomelanocortin (POMC), a precursor of various polypeptides with potent anorexigenic activity.

This study investigated whether POMC‐specific neuronal density in the ARC was different in OP versus OR mice. For this purpose, 16 C57BL/6J POMC‐EGFP mice (which express the Green Fluorescent Protein (GFP) concomitantly with POMC) were fed during 11 weeks with a HFHS diet and a 12.6% sucrose‐sweetened drink (SSW) (concentration found in sodas) given at random periods of time for 2h. At the end of this period, 4 OP mice and 4 OR mice were selected, according to their body weight and fat mass gain.

Measurement of food and liquid intake showed that OP mice ate more solid food than OR mice. At the end of the experiment, the brains of OR and OP mice were fixed and cut into coronal sections covering the whole hypothalamic area of the ARC. These sections were digitized and analyzed to obtain three‐dimensional reconstructions of the ARC area, using Free‐D original software. The results show no quantitative difference in POMC expression in the ARC between OP and OR mice. However, statistical analysis of 3D reconstructions showed significant differences between OR and OP mice in the spatial organization of POMC‐expressing neurons in the ARC. This study characterizes the synaptic plasticity of POMC neurons between OP and OR mice, that could be a major factor of their difference in susceptibility to weight gain.
DHA status is related to prefrontal cortex‐mediated impulse control in adolescents
Authors: Darcey Valerie L. , El Damaty Shady , Rose Emma J. , Fishbein Diana H. , VanMeter John W.
Published: November 2023

The emergence of impulse control, a function mediated by the prefrontal cortex (PFC), is critical for avoiding risky behaviors during adolescence. The PFC is undergoing development during this period and thus influences on its maturation may contribute to variations in impulse control. One such factor is docosohexoenoic acid (DHA), an essential omega‐3 fatty acid that influences neuronal function, particularly in the PFC. Though DHA is an integral structural component of neuronal membranes, little is known about the relationship between DHA status, structural qualities of PFC and impulse control in adolescents. Thus, this study examined adolescent PFC thickness and behavioral inhibition in relation to DHA status.

Teens (n=53; 51% female; mean age 14.3 ± 0.7 years) enrolled in a longitudinal neuroimaging study provided blood samples (i.e., dried blood spot) for analysis of essential fatty acids via high‐pressure liquid chromatography. At the same study visit, we assessed behavior and obtained brain scans. Ability to inhibit a prepotent response was assessed by frequency of commission errors (false alarms) on a Go/No‐go task. High‐resolution structural brain scans (MPRAGE) were acquired on a Siemens TIM Trio 3T MRI and verified for quality. Recruitment of the right inferior frontal gyrus (IFG) has been consistently implicated in behavioral inhibition and, thus, was the focus of this cortical thickness analysis using Freesurfer.

DHA was significantly inversely correlated with impulsive errors on the Go/No‐Go task (r= −0.368; p=0.018). A trending inverse relationship was also observed between impulsive errors and the thickness of right IFG (pars triangularis) (r=−0.247; p=0.074). Blood DHA content was unrelated to potential confounding variables (e.g., age, intelligence, or socioeconomic status).

These preliminary results suggest that higher DHA status may be related to a greater ability to inhibit a prepotent behavioral response, i.e., behavioral/impulse control. Furthermore, the potential relationship between IFG cortical thickness and response inhibition echoes previous findings that development of this region is important for behavioral control. Together these results suggest that insufficient dietary DHA intake during adolescence may hinder development of behavioral control. This development may be important for reducing risky decision making related to high‐risk behaviors (e.g. drug and alcohol use) during this development period and warrants further investigation.

Support or Funding Information

NIH/NIAAA 1R01AA019983‐01 (DHF/JVM), 3R01AA019983‐02S1 (VLD)and 1F31AA023462‐01A1 (VLD)
Changes in Eating Behaviors are Associated with Intentional Weight Loss Following Intervention in Older Women
Authors: Berg Alison C , Johnson Kristen B , Straight Chad R , Acitelli Rachel M , O'Connor Patrick J , Evans Ellen M , Johnson Mary Ann
Published: November 2023

Purpose

Obesity prevalence in older women (≥ 60 y) exceeds 35% and the literature strongly suggests that weight loss improves chronic conditions and physical function in this age group. Studies in younger people indicate that many dieters fail to achieve weight loss goals, and that psychological constructs, particularly eating behaviors and depressive symptoms, may play a role; however, limited research exists evaluating the role of these constructs in weight loss success in older women. Thus, this study aimed to examine relationships among eating behaviors, depressive symptoms, and weight loss in overweight and obese older women.

Methods

Older women (N = 72; 69.4 ± 3.6 y, BMI 31.2 ± 4.9) completed assessments of eating behaviors (Three Factor Eating Questionnaire), depressive symptoms (Centers for Epidemiologic Studies Depression Scale), and body weight at baseline and following a weight loss intervention that combined restriction of energy intake and exercise training with a goal of loss of 10% of initial body weight. Changes in psychological measures and weight from baseline to post‐intervention were assessed with paired t‐tests and Wilcoxon‐rank sum tests (non‐parametric data) and effect sizes (ES) calculated. A series of linear regression analyses were used to explore the independent contribution of the psychological constructs to weight loss among completers of the intervention (N = 61).

Results

Weight loss was −9.2 ± 4.8 % of initial weight. Measures of restrained eating behavior increased significantly (P < 0.0001) from baseline to post‐intervention (ES > 1.2). An increase in flexible restraint accompanied by a decrease in rigid restraint explained a significant proportion of the variance in percent weight loss when controlled for energy intake (% of needs at baseline and changes in intake; overall R2=.26, F(4,56) = 4.91, P < 0.01). Depressive symptoms were not related to weight loss, but were more prevalent in individuals who withdrew from the study after baseline testing (P < 0.001).

Conclusions

Encouraging a flexible approach to eating behavior and discouraging rigid restraint of eating behavior may lead to better weight loss outcomes for overweight and obese older women trying to lose weight. Although not associated with weight loss following intervention, depressive symptoms in older overweight or obese women may be a risk factor for withdrawing from weight loss studies.

Support or Funding Information

Funded in part by The Beef Checkoff and USDA NIFA GEO 708
Cereal foods consumption trends and factors associated with changing intake, among Western Australian adults, 1995 to 2012
Authors: Pollard Christina Mary , Pulker Claire , Meng Xingqiong , Denham Felicity , Solah Vicky , Scott Jane A , Kerr Deborah A
Published: November 2023

Background

Regular adequate cereal foods intake, particularly wholegrains, may protect against cardiovascular disease, diabetes, and excess weight gain. Knowledge, attitudes and perceived barriers influence attempts to change intake. Trends in self‐reported cereal food consumption and factors influencing intake among Western Australian adults are assessed.

Methods

Data were pooled from the 1995, 1998, 2001, 2004, 2009, and 2012 Health Department's Nutrition Monitoring Survey Series of 7,044 adults, 18 to 64 years. Outcomes: type and amount of cereals (bread, rice, pasta, breakfast‐cereal) eaten the day prior. Attitudes, knowledge, intentions regarding cereal food intake and weight control and sociodemographics were measured. Descriptive statistics, multiple linear or logistic regressions assess factors associated with consumption, knowledge and attitude.

Results

Bread (78%) and breakfast‐cereal (50%) were most commonly consumed. The proportion eating bread reduced from 2001 (OR=0.31; 95% CI 0.24–0.40 in 2012 compared to 1995) as did the amount (4.1 slices in 1995 to 2.4 in 2012). Males were more likely to eat bread (OR=1.44; 1.23–1.68; p<0.001) and breakfast‐cereal (OR=1.18; 1.04–1.34; p<.05). ‘I already eat enough’ was the main barrier to increasing cereals (75% in 1995 to 84% in 2012 (p<.001)). Knowledge of recommended daily serves decreased over time (OR=0.20; 0.15–0.27; p<0.001) and relative risk ratios of having tried to eat less over the past year increased (RRR 10.88, CI 6.81, 17.4), 2012 compared to 1995. Overweight (RRR 1.65, CI 1.22, 2.24) and obese (RRR 1.88, CI 1.35, 2.63) respondents were more likely than normal weight to have tried to eat less cereals.

Conclusions

A growing proportion of adults are actively trying to reduce the amount of cereal foods they eat associated with a lack of knowledge about the amount to eat for health. Health promotion intervention is needed to increase awareness of the health benefits of eating more cereal foods and address the barriers to incorporating them daily.

Support or Funding Information

Healthway funded Curtin University's Food Law, Policy and Communications to Improve Public Health Project to assist the translation of research into practice
Whey and Pea Protein Influence Energy Metabolism and Appetite Response to a Greater Extent Than Beef Protein
Authors: Neumann Brianna L , Cambias Lauren , Mitchell Charlene , Silva Enela , Baum Jamie I
Published: November 2023

More than 30% of young adults in the US are obese. A primary contributor to obesity is an unhealthy diet related to an imbalance of macronutrients. Diets higher in protein (PRO) are associated with health benefits such as increased energy expenditure (EE) and reduced food intake. The objective of this pilot study was to determine if protein source at breakfast influences EE in young men (n=5; ages 18–35). Participants consumed four isocaloric protein‐based beverages (whey (WP), pea (PP), beef (BP); 275 kcal‐62%PRO:23%CHO:15% Fat) for breakfast in randomized, crossover design with a one‐week washout period between beverages. Each test day EE, appetite and food preference were assessed at 0, 15, 30, 60, 120, 180, and 240 min postprandial. Data was analyzed using a 2‐way ANOVA for the effect of protein source over time. One‐way ANOVA was used to analyze area under the curve (AUC). Resting EE AUC was 8% lower in BP vs PP and 5% lower vs WP. Thermic effect of feeding AUC was 77% lower (P = 0.08) in BP compared to WP; PP was 43% lower than WP. Postprandial carbohydrate oxidation was higher with PP (31%) compared to WP and there was no difference between BP and WP. Postprandial fat oxidation was 23% higher in WP vs BP and PP. WP was more satiating compared to BP and PP, however participants had a higher craving for sweet foods following PP and a higher desire for a snack following BP. Taken together, these data suggest that protein source (animal versus plant) is not a predictor of postprandial EE and appetite response.

Support or Funding Information

Arkansas Biosciences Institute
Effects of Increased Dietary Protein on Daily Appetite Control, Satiety, and Free‐living Ad Libitum Food Intake during Acute Energy Restriction in Healthy, Overweight Women
Authors: Gwin Jess A
Published: November 2023

Background

Higher‐protein (HP) energy restriction (ER) diets improve body composition and weight management to a greater extent than standard‐protein (SP) versions. Improvements in appetite and satiety are proposed mechanisms‐of‐action. However, most mechanistic studies are limited by the lack of acclimation to the study treatments; the failure to match protein quality between study treatments; and the absence of daily, ad libitum feeding assessments.

Purpose

To investigate the effects of consuming SP vs. HP diets on daily appetite control, satiety, and ad libitum food intake in healthy, overweight women during ER.

Methods

Seventeen women (age: 36±1y; BMI: 28.4±0.1kg/m2) completed the following randomized, controlled‐feeding, cross‐over design study. Participants consumed 3 ER diets (1250 kcal/d) containing SP (15% of energy from protein; 48g protein/d) or HP (40% of energy from protein; 124g protein/d). The SP diets contained all plant proteins (PLANT) or a combination of beef and plant proteins (BEEF), whereas HP contained BEEF. Breakfast, lunch, dinner, and an evening snack were provided for 7 days/diet. On day 6 of each pattern, participants completed a tightly‐controlled 12‐h testing day consisting of questionnaires assessing perceived hunger, fullness, desire to eat, prospective food consumption (PFC), and food cravings. On day 7, protein intake was held constant but carbohydrate and fat‐rich foods were provided ad libitum at each meal and snack.

Results

HP‐BEEF led to a 20% reduction in daily hunger (p<0.05) and a 15% increase in daily fullness (p<0.05) vs. both SP diets. HP‐BEEF also led to a 21% reduction in daily desire to eat (p<0.05) and a 17% reduction in PFC (p<0.05) vs. both SP diets. Cravings for fast‐foods and total food cravings were lower following HP vs. both SP diets (both, p<0.05). By design, daily protein intake was greater following HP vs. SP diets (p<0.05). However, ad libitum carbohydrate and fat intake were not voluntarily reduced following the HP vs. SP diets (Figure 1; p<0.05). Lastly, no differences in any study outcomes were detected between the SP‐PLANT vs. SP‐BEEF diets.

Conclusions

Although appetite control and satiety were improved following a high‐protein, energy restriction diet compared to standard‐protein versions, increased protein consumption did not reduce free‐living daily food intake in overweight, healthy women exposed to ad libitum, highly palatable foods.

Support or Funding Information

The Beef Checkoff
Dietary Enrichment with Blueberry and/or Probiotics Does Not Alter Blood Pressure Variability Compared to Control Diet in Hypertensive Rats
Authors: Blanton Cynthia , He Zhengcheng , Gottschall‐Pass Katherine T. , Sweeney Marva I.
Published: November 2023

Variability in blood pressure (BP) is a risk factor for cardiovascular events independent of mean BP. Recently we showed that feeding polyphenol‐rich wild blueberries (BB) or probiotics (PRO) to hypertensive rats reduced the characteristic rise in BP over time. Here we report the effect of these diets on BP variability. Groups (n=8 each) of male spontaneously hypertensive rats were fed one of four AIN93G‐based diets for 8 weeks: Control; 3% freeze‐dried wild BB; 1% probiotic bacteria (PRO); or 3% BB + 1% PRO. BP was measured biweekly by the tail‐cuff method. The standard deviation (SD) and coefficient of variation (CV) of diastolic and systolic BP were compared across groups using 2‐way ANOVA with repeated measures.

Results

Separate diet enrichment with BB or PRO did not have a significant effect on BP variability (p>0.10). However, the interaction of enrichment with BB and PRO had a significant effect on diastolic BP SD (p=0.016) and CV (p=0.007), with post‐hoc comparisons showing lower variability in the BB+PRO vs. BB group (p<0.05). BP variability was not different from control for any enriched diet.

Conclusion

Diet enrichment with separate or combined BB and PRO does not affect BP variability compared to control diet in hypertensive rats. Adding PRO to BB‐enriched diets might alter BP variability.

Support or Funding Information

Wild Blueberry Association of North America
Dietary Red Raspberries Supplementation Ameliorates Dextran Sulfate Sodium‐Induced Acute Colitis
Authors: Bibi Shima , Kang Yifei , Du Min , Xue Yansong , Zhu Mei‐Jun
Published: November 2023

Introduction

The ability to elicit an inflammatory response to pathogenic microbes or foreign subjects is a critical protective mechanism for host survival; however, persistent intestinal inflammation severely impairs intestinal integrity and can result in inflammatory bowel diseases and further increases the likelihood of developing colorectal cancer. Red raspberries (RRS) are a rich source of polyphenolic compounds that are known for their anti‐oxidative and anti‐inflammatory effects. However, the beneficial effects of whole red raspberries on the colitis models have not been studies.

Objective

This study was to evaluate beneficial effects of RRS supplementation on colitis protection using a dextran sulfate sodium (DSS) induced acute colitis mice model.

Methods

6‐wk‐old wild‐type male mice (C57BL/6) were fed with a standard rodent diet supplemented with RRS (0 or 5% of dry feed weight) for 6 weeks. At 4th week of dietary treatment, colitis was induced by supplementation with 2.5% DSS in drinking water for 6 days, followed by 6 days of recovery, when mice were necropsied and tissue were collected for later histological and biochemical analyses.

Results

RRS supplementation had no effect on body weight gain and feed intake in mice without DSS‐induced colitis. In DSS‐induced groups, all mice on both standard diet and raspberry supplemented diet survived during DSS treatment and recovery period. RRS supplementation decreased body weight loss, diminished diarrhea and gross bleeding, and ameliorated the disease activity index associated with diminished colon shortening induced by DSS treatment. In addition, RRS supplementation protected the architecture of distal colon from severe damage induced by DSS and decreased neutrophil infiltration in colon of DSS induced mice. Furthermore, RRS supplementation down‐regulated cyclooxygenase‐2 (COX‐2) protein expression and activated p38 mitogen‐activated protein kinase (MAPK) signaling in DSS‐mice.

Conclusion

RRS supplementation ameliorated colitis symptom in DSS induced colitis mice possibly through its anti‐inflammatory effect. (NATL PROC RASPBERRY CNCL)

Support or Funding Information

NATL PROC RASPBERRY CNCL
Higher Adherence to the Mediterranean Diet Score, but not other Diet Quality Scores, is Associated with a Favorable Longitudinal Cardiometabolic Profile in the Boston Puerto Rican Health Study
Authors: Mattei Josiemer , Sotos‐Prieto Mercedes , Noel Sabrina E , Tucker Katherine L
Published: November 2023

Diet quality scores have been used to evaluate adherence to specific dietary recommendations or to consumption of healthful foods and nutrients. Few studies have assessed the strength of the associations between several diet quality scores and longitudinal cardiometabolic profile, and it remains unknown which score can best predict cardiometabolic risk factors in at‐risk ethnic minority populations. We aimed to contrast longitudinal associations of four diet quality scores (American Heart Association Diet Score (AHA‐DS), Dietary Approaches to Stop Hypertension score (DASH), the Healthy Eating Index‐2005 (HEI), and a Mediterranean Diet Score (MeDS)) calculated from baseline dietary data obtained from a validated food frequency questionnaire and 2‐y follow‐up measures of 14 individual cardiometabolic risk factors in the Boston Puerto Rican Health Study (n=1,251, ages 45–75y at baseline). Multivariable‐adjusted repeated‐subjects mixed‐effects models were used to determine the association between z‐scores of each diet quality score and cardiometabolic risk factors over 2 years. The MeDS was significantly associated with decreased waist circumference (β‐coefficient (standard error) =−0.539 (0.268), p=0.044); body mass index (−0.236 (0.082), p=0.004); log‐insulin (−0.047 (0.022), p=0.027); log‐Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR, −0.053 (0.025), p=0.034) and log‐C‐reactive protein (−0.091 (0.036), p=0.011), and marginally significant with waist‐to‐hip ratio (−0.004 (0.002), p=0.05). The HEI was positively associated with LDL‐cholesterol (2.00 (0.924), p=0.031), and neither AHA‐DS nor DASH were associated with any longitudinal value. In conclusion, higher adherence to the MeDS at baseline is associated with a favorable cardiometabolic profile in the subsequent 2 years. The results could help nutrition researchers and health professionals select suitable measures of diet quality in epidemiological studies, as well as craft effective nutritional messages and programs that focus on meaningful dietary recommendations for this at‐risk minority group.

Support or Funding Information

Funded by the NIH‐National Heart Lung and Blood Institute (NHLBI) P50 HL105185, and by the NHLBI K01‐HL120951 Mentored Career Development Award to Promote Faculty Diversity in Biomedical Research.
A Review and Meta‐Analysis of Prospective Studies of Red and Processed Meat, Meat Cooking Methods, Heme Iron, Heterocyclic Amines and Prostate Cancer
Authors: Bylsma Lauren C , Alexander Dominik
Published: November 2023

Prostate cancer remains a significant public health concern among men in the U.S. and worldwide. Epidemiologic studies have generally produced inconclusive results for dietary risk factors for prostate cancer, including consumption of red and processed meats. We aimed to update a previous meta‐analysis of prospective cohorts of red and processed meats and prostate cancer with the inclusion of new and updated cohort studies, as well as evaluate meat cooking methods, heme iron, and heterocyclic amine (HCA) intake exposure data. A comprehensive literature search was performed and 26 publications from 19 different cohort studies were included. Random effects models were used to calculate summary relative risk estimates (SRREs) for high vs. low exposure categories. Additionally, meta‐regression analyses and stratified intake analyses were conducted to evaluate dose‐response relationships. The SRREs for total prostate cancer and total red meat consumption, fresh red meat consumption, and processed meat consumption were 1.02 (95% CI: 0.92–1.12), 1.06 (95% CI: 0.97–1.16), and 1.05 (95% CI: 1.01–1.10), respectively. Analyses were also conducted for the outcomes of non‐advanced, advanced, and fatal prostate cancer when sufficient data were available, but these analyses did not produce significant results. No significant SRREs were observed for any of the meat cooking methods, HCA, or heme iron analyses. Dose‐response analyses did not reveal significant patterns of associations between red or processed meat and prostate cancer. In conclusion, the results from our analyses do not support an association between red meat or processed consumption and prostate cancer, although we observed a weak positive summary estimate for processed meats.

Support or Funding Information

This work was supported in part by the National Cattlemen's Beef Association (NCBA), a contractor to the Beef Checkoff. NCBA did not contribute to the writing, analysis, interpretation of the research findings.
The Relative Reinforcing Value of Snack Foods in Response to Consumption of Sugar‐ or Non‐Nutritive‐Sweetened Beverages
Authors: Casperson Shanon L , Johnson LuAnn , Roemmich James N
Published: November 2023

The effects of sugar and non‐nutritive sweetener on the regulation of appetite and energy intake remain controversial. Using a behavioral economic choice paradigm, we sought to determine the effects of consuming a sugar‐sweetened (S) or a non‐nutritive sweetened (NNS) beverage on appetite and the relative reinforcing value (RRV) of snacks foods. In a randomized crossover study, 11 normal weight adults (age = 22.6 ± 2.8; BMI = 23 ± 2) consumed 360 ml of S (31g) or NNS (sucralose; 4g) beverage with a standardized meal (500 non‐beverage kcals). Hedonic (liking) ratings for high‐sugar and savory snack foods were assessed prior to the start of the study. Satiety and the desire to eat sweet and savory foods were assessed before and every 30 minutes post‐meal. The RRV of snack foods was assessed 4 hrs post‐meal using a computer choice task (operant responding with concurrent schedules of reinforcement). Subjects could choose to earn points for 70 – 100 kcal portions of their favorite high‐sugar (e.g. M&Ms) or savory (e.g. Doritos) snack food. The behavioral cost to gain access to each snack food increased on independent and concurrent log2(x) reinforcement schedules. The RRV of the snack foods was assessed as the amount of operant responding (button presses) subjects engaged in for either choice relative to the total number of responses. Hedonic ratings did not differ between the chosen high‐sugar and savory snack foods. Beverage type did not influence measures of satiety or the desire to eat specific types of foods. Subjects performed an average of 364 ± 445 and 179 ± 106 button presses for high‐sugar snack foods and 213 ± 252 and 518 ± 568 for savory snack foods after consuming NNS and S, respectively. The RRV of snack foods indicates that high‐sugar snack foods are more reinforcing after consuming NNS and savory snack foods are more reinforcing after consuming S (p < 0.05). In conclusion, our preliminary choice and consumption results indicate that beverage type can influence the motivation to gain access to different types of foods later in the day.

Support or Funding Information

Study was supported by ARS‐USDA.
Influence of Daily and Per Meal Protein Intakes on Function and Body Composition in Frail, Obese Older Adults Undergoing Weight Reduction
Authors: Starr Kathryn N Porter , Orenduff Melissa C , McDonald Shelley R , Pieper Carl F , Mulder Hillary C , Maloney Kathleen , Bales Conne W
Published: November 2023

Recent recommendations that older adults consume 25–30 g high quality protein at each meal are based on evidence that enhanced protein intake will benefit aging muscles. We studied this possibility during geriatric obesity reduction, with the goal of preferentially protecting lean mass and function during weight loss. This 6‐month randomized controlled trial of weight reduction in obese (BMI ≥30 kg/m2), older (≥60 years) men and women with physical frailty (Short Physical Performance Battery [SPPB] score 4–10), randomized to a control (n = 13; Control) or an enhanced protein (n = 26; Protein) arm explores the influence of >25 g protein per meal during weight loss on function (SPPB) and lean mass. At 6 months, weight losses were 9.2% for Control and 10.1% for Protein. Intakes of protein assessed by 3‐day record differed by group for total intake (69.6 ± 19.9 g for Control, 111.0 ± 36.8 g for Protein; P < 0.0001) and average meal protein intake (20.9 ± 6.0 g for Control, 33.9 ± 10.4 g for Protein; P < 0.0001). The Protein group increased SPPB score by 2.4 ± 1.7 units, while the Control group increased SPPB by 0.9 ± 1.7 units, indicating a protein benefit to function (P = 0.02). Lean mass decreased in both Control (−1.8 ± 2.9 kg; P < 0.01) and Protein (−1.1 ± 1.5 kg; P < 0.01), with no group difference. We evaluated relationships of protein intake [for the total group] with changes in lean mass and SPPB score. There was no relationship to lean mass change; however, change in SPPB score was associated with total protein intake (rs = 0.33, P < 0.05) and percent of meals reaching 25 g protein (rs = 0.43, P < 0.01), underscoring the protein/function connection. For obese, frail older adults undergoing a weight loss intervention, a high quality protein‐enhanced diet was superior in improving physical function compared to the Control diet. These findings illustrate the potential importance of enhanced protein intake (daily total and amount per meal) during obesity reduction for restoring function in this vulnerable population.

Support or Funding Information

This study was funding by the Beef Checkoff Program and received additional support from the National Institutes of Health (5T32 AG000029 to KNPS; 1P30 AG028716 to CFP).
Multipronged Therapeutic Mechanisms of Chinese Herbal Medicine QHD in the Treatment of NAFLD
Authors: Feng Qin , Liu Wensheng , Baker Susan S , Li Hongshan , Meng Shengxi , Tang Yajun , Tang Shijie , Guan Lingyu , Tsompana Maria , Kozielski Rafal , Zhu Ruixin , Baker Robert D , Peng Jinghua , Ji Guang , Liu Ping , Hu Yiyang , Zhu Lixin
Published: November 2023

Clinical studies have demonstrated the therapeutic efficacy of the Chinese herbal medicine Qushi Huayu Decoction (QHD) in the treatment of non‐alcoholic fatty liver disease (NAFLD). It has been suggested that QHD reduces hepatic lipid accumulation through its regulatory effect on liver fat metabolism. Herein, to better understand the pharmaceutical mechanisms of QHD, we aimed to investigate the effect of QHD on gut‐liver axis using systems biology approaches. High‐fat diet (HFD) ‐induced rat NAFLD models were treated with QHD or a mixture of two active components of QHD (geniposide and chlorogenic acid, GC). Liver pathology and blood biochemistry were conducted to evaluate the effects of QHD and GC therapy. To understand the molecular mechanisms of the therapeutic effects, global microarray expression analysis of the liver genes was conducted and validated by quantitative RT‐PCR. To evaluate the effect of GC therapy on the gut microbiome and NAFLD, we used NAFLD rats induced by HFD and dextran sulfate sodium (DSS) to ensure increased gut permeability. With both NAFLD rat models, QHD and GC treatments caused reduced weight gain, liver fat, liver transaminases, and lymphocyte infiltration. We also observed down‐regulation of genes and pathways in lipid metabolism and inflammation, consistent with the beneficial effects of QHD and GC therapy. Decreased expression of genes for lipid synthesis, and increased expression of genes for production of the antioxidant glutathione represent two possible mechanisms for QHD and GC therapy. GC treatment decreased serum LPS in NAFLD rats, which is not explained by the change of microbiota composition, as microbiome analysis revealed increased abundance of Gram‐negative bacteria in GC treated rats. Rather, decreased serum LPS and TLR4 signaling in the liver could be explained by reduced mucosal damage in the colon of GC‐treated rats. In the gut of GC‐treated rats, increased abundance of Treg‐inducing bacteria may down‐regulate inflammatory signals and consequently improve gut barrier function. Our study provides strong support that QHD and its active components simultaneously target lipid synthesis, the anti‐oxidative mechanism and gut microbiota, offering a possible treatment for NAFLD.

Support or Funding Information

This work is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (U01 DK061728, to S.S.B.), the Peter and Tommy Fund, Inc., Buffalo, NY (to S.S.B. and L. Z.), the National Natural Science Foundation of China (No. 81374031, to Q. F.), the National Natural Science Foundation of China (No. 81173404, to Y. H.) and a departmental start‐up fund (to L.Z.).
Prospective Association of Fasting Blood Glucose Levels with Risk of Incident Stroke among Hypertensive Patients in China: Impact of Folic‐acid Intervention
Authors: Xu Richard , Kong Xiangyi , Xu Benjamin , Ji Meng , Zhang Yan , Wang Binyan , Hou Fan Fan , Ge Junbo , Huo Yong , Li Jianping
Published: November 2023

Background

Diabetes has been shown to independently increase the risk of ischemic stroke. Aside from conventional clinical intervention (blood pressure control and cholesterol lowering), uncertainty remains on the role of folic acid supplementation in preventing stroke among individuals with elevated glucose, in particular, in low folate regions such as China.

Objectives

This study sought to address two questions: (1) what is the prospective relationship between baseline blood glucose levels (ranging from normal, prediabetes to diabetes) and incident stroke risk? (2) can folic acid supplementation reduce the risk of stroke in hypertensive patients with elevated blood glucose levels?

Methods

This analysis included 20,313 hypertensive adults without history of stroke or myocardial infarction (MI) in the China Stroke Primary Prevention Trial (CSPPT), who were randomly assigned to a double‐blind daily treatment with 10mg enalapril and 0.8mg folic acid (n=10,348) or 10mg enalapril alone (n=10,354). Kaplan‐Meier survival analysis and Cox proportionate hazard models were used to estimate the effect of fasting blood glucose levels and folic acid therapy on first stroke risk, adjusting for pertinent covariates.

Results

During a median treatment duration of 4.5 years, 615 participants developed first stroke. High fasting blood glucose level (≥7.0 mmol/L) or diabetes, compared to low level (<5.6 mmol/L), was associated with increased risk of first stroke (5.1% versus 2.7%, HR, 1.6; 95%CI, 1.3–2.0; p‐value <0.001). Importantly, an inverse association between glucose and stroke was observed even at glucose levels far below current clinical cutoff for diabetes. Folic acid supplementation can significantly reduce the risk of stroke across a wide range of elevated glucose levels. The risk reduction was the greatest among those with fasting blood glucose level ≥7.0 mmol/L or diabetes (35%, HR, 0.65, 95%CI, 0.45–0.95, P<0.001). These findings were mainly observed in ischemic stroke.

Conclusion

Among adults with hypertension but without history of stroke and MI in China, higher fasting blood glucose levels (even still within the normal range) were associated with increased risk of ischemic stroke. Folic acid therapy can significantly reduce the risk of ischemic stroke among hypertensive patients with elevated blood glucose levels. Our findings warrant additional investigation and suggest that folic acid may offer a simple, safe, and effective strategy to further reduce the risk of first stroke among hypertensive patients with elevated blood glucose levels.
Four a priori‐defined Diet Quality Indexes and Survival among Men and Women with Colorectal Cancer: The Multiethnic Cohort
Authors: Maskarinec Gertraud , Jacobs Simone , Harmon Brook E , Wilkens Lynne R , Le Marchand Loic , Kolonel Laurence N , Boushey Carol J
Published: November 2023

Background

Given the increasing number of colorectal cancer (CRC) survivors, the possible effect of modifiable health behaviors, in particular optimal nutrition, on prognosis is critical. In recent years, the idea has emerged that dietary patterns may be better suited to capture the complexity of dietary intake than the analysis of single foods or nutrients. We investigated the association between four a priori dietary quality indexes assessed 6.0±4.7 years before diagnosis and CRC‐specific survival in the Multiethnic Cohort (MEC).

Methods

At baseline, more than 215,000 African American, Native Hawaiian, Japanese American, Latino, and white adults completed a validated quantitative food frequency questionnaire designed to capture dietary intake in the five relevant ethnic groups. Colorectal cancer cases and deaths from all causes were identified through linkages to SEER cancer registries and the National Death Index. Cox proportional hazards regression was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the Healthy Eating Index‐2010 (HEI‐2010), the Alternative HEI‐2010 (AHEI‐2010), the Alternate Mediterranean Diet Score (aMED), and the Dietary Approaches to Stop Hypertension (DASH) while adjusting for relevant confounders.

Results

Among 4,204 MEC participants diagnosed with invasive CRC cases during follow‐up, 1,976 all‐cause and 1,095 CRC‐specific deaths were identified. CRC‐specific survival was significantly associated with higher scores on the HEI‐2010 (ptrend=0.04); for one standard deviation increase in the HEI‐2010, the HR was 0.93 (95%CI: 0.88–0.99). Individuals in the highest vs. lowest diet quality quartile experienced 20% lower mortality (HR=0.80; 95%CI: 0.67–0.97). A higher aMED score was associated with borderline lower CRC mortality (HR=0.94; 95%CI: 0.88–1.01; ptrend=0.09). No significant associations of CRC‐specific survival with the DASH and AHEI‐2010 indexes were detected.

Conclusions

The current findings may be related to the HEI‐2010 inclusion of dairy intake as a positive dietary component and added sugars from all sources as a negative one. Also, scores for the HEI‐2010 and aMED are positively influenced by fish intake and a higher ratio of unsaturated to saturated fatty acids, which are considered possible preventive factors. These results emphasize the merit of an overall healthful diet for optimal survival outcomes.

Support or Funding Information

The Multiethnic Cohort Study has been supported by grants R37CA54281 and UM1CA164973 from the National Cancer Institute. Dr. Harmon was supported by postdoctoral fellowships on grant R25CA90956. The tumor registries are supported by NCI contracts N01 PC 35137 and N01 PC 35139.