bluuebunny/crossref_metadata_2025 huggingface dataset:
Inactivation of Pyruvate Dehydrogenase Complex Mediates The Selective Effects of Butyrate on Colorectal Cancer Cells.
Authors: Han Anna , Bennett Natalie , MacDonald Amber , Johnstone Megan , Whelan Jay , Donohoe Dallas R.
Published: November 2023

Butyrate, derived from the microbial fermentation of dietary fiber in the colon, is utilized as the primary energy source in the colonocyte. Butyrate can also regulate gene expression through inhibition of histone deacetylases (HDACs) in cancerous colonocytes. Butyrate has been reported to have selective effects on colorectal cancer cells where it slows cellular proliferation and induces apoptosis. Previously, we found that oxidation of butyrate is diminished in cancerous colonocytes compared to non‐cancerous colonocytes, and this difference in metabolism impacts the inhibition of HDACs by butyrate. The primary aim of this study was to characterize the mechanisms that influence butyrate oxidation in cancerous colonocytes (HCT116). We hypothesized that the decrease in butyrate oxidation observed in the cancerous colonocyte is associated with enhanced glucose uptake and utilization (the Warburg effect). Colorectal cancer cells increase glycolysis and decrease oxidative metabolism through the phosphorylation and inactivation of the pyruvate dehydrogenase complex, which pushes cellular metabolism away from the formation of acetyl‐CoA and mitochondrial respiration. We chose to target the inactivation of the pyruvate dehydrogenase complex as a major event in regulating the Warburg effect and decreasing butyrate oxidation in the colorectal cancer cell. In these experiments, the Seahorse XF24 Analyzer was used to measure butyrate oxidation in HCT116 cells with and without dichloroacetate (DCA). DCA is a PDH kinase inhibitor that increases PDH activation. We report here that the oxidation of butyrate in colorectal cancer cells with DCA was significantly higher than those without DCA (p<0.05). Next, we tested whether the inactivation of PDH in decreasing the oxidation of butyrate was dependent upon carnitine. Towards this end, DCA did not elevate butyrate oxidation in cancerous colonocytes when carnitine was absent (p<0.05). Furthermore, inactivation of PDH was associated with decreased OCNT2 (a major carnitine transporter) and CPT1A (carnitine palmitoyltransferase 1A) expression, which both have key roles in regulating carnitine‐dependent fatty acid oxidation. These data suggest that inactivation of PDH results in decreased butyrate oxidation that is dependent upon carnitine, and provide insight into why colorectal cancer cells are sensitive to butyrate.
Capsaicin Inhibits Methionine Cotransport in Rat Intestinal Epithelial Cells
Authors: Talukder Jamil , Hill Cameron Cameron , Jaima Antara , Santiz‐Lopez Jessica
Published: November 2023

Background

Intestinal absorption of nutrients is a vital mechanism that depends essentially on the function of intestinal mucosa. Foodborne phytochemicals or bioactive compounds can play an important role in the mediation of Na+‐dependent nutrient transport from the gut lumen. The effect of chili extract (capsaicin) on absorption of essential amino acids is unknown.

Aim

To determine the effect of capsaicin on Na+‐dependent Met cotransport in enterocytes.

Methods

IEC‐6 cells grown on transwell plates were treated with capsaicin. Initially, dose response and time course experiments were performed for Met uptake using [3H]‐Met. Cytosolic Ca2+ was measured using Flu 3AM and Caspase‐3 activity was determined using a kit. RTQ‐PCR and Western blot analyses were performed to determine SNAT2 mRNA and protein levels, respectively.

Results

Capsaicin treatment decreased Na+‐dependent Met uptake dose dependently in IEC‐6. Kinetic studies demonstrated that capsaicin inhibits Met uptake by decreasing the number of Met cotransporters. Capsaicin treatment increased cytosolic Ca2+ levels and Caspase‐3 activity. Molecular studies showed that SNAT2 mRNA levels and SNAT2 protein on apical membrane were down regulated by capsaicin.

Conclusion

These studies revealed that capsaicin inhibits Met cotransport, SNAT2 in enterocytes.

Support or Funding Information

This work was supported by National Science Foundation Grants HRD‐1332459
SERUM 25‐HYDROXY D3 LEVELS IN NONALCOHOLIC FATTY LIVER DISEASE
Authors: Goktas Zeynep , Galyean Shannon , Syn David , Koklu Seyfettin , Wang Shu , Boylan Mallory , Dikmen Derya , Uyar Banugul
Published: November 2023

Background

It has become the most common liver disease in the world. Nonalcoholic fatty liver disease (NAFLD) is a wide range of disorders from a simple steatosis to fibrosis/cirrhosis. Although some studies show association between vitamin D and NAFLD; studies showing the association in different severity of NAFLD are limited.

Aim

The aim of this study to evaluate serum 25‐hydroxy vitamin D 3 levels in different severity of NAFLD.

Materials and Methods

Fifty three morbidly obese subjects (BMI ≥40 kg/m2) were included into the study. NAFLD activity scores (NAS) were calculated according to liver biopsies and subjects were divided into 3 group; mild NAFLD (n =15, NAS score: ≤2), moderate NAFLD (n =23, NAS score: 3–4), severe NAFLD (n =15, NAS score: ≥5). Blood samples were collected. Liquid chromatography/tandem mass spectrometry was used to analyze the serum vitamin D levels.

Results

Serum 25‐Hydroxy vitamin D 3 levels were significantly lower in moderate and severe NAFLD groups (25.9 ± 9.10 ng/ml and 21.9 ± 7.14 ng/ml, respectively) than the mild NAFLD group (34.5 ± 10.19 ng/ml). Total cholesterol and HDL cholesterol levels were lower in severe NAFLD group (165.0 ± 38.64 mg/dl and 39.8 ±8.33 mg/dl). Furthermore, serum folic acid levels were significantly lower in moderate and severe NAFLD groups (13.8 ± 4.00 nmol/L and 14.9 ± 4.38 nmol/L, respectively) than mild NAFLD group (17.9 ± 3.98 nmol/L). Serum 25‐ Hydroxy D 3 levels and NAS were not significantly different between gender groups. Serum vitamin D levels showed an inverse correlation with NAS (r = −0.332, p < 0.05). NAS levels did not show any significant difference between gender groups.

Conclusion

Serum 25‐Hydroxy vitamin D 3 levels may differ in different severity of NAFLD.
Effect of Dietary Pulse Consumption on Blood Pressure
Authors: Stewart Sarah E , Ireland Christopher A , de Souza Celine , de Souza Russell J , Mitchell Sandra , Augustin Livia S , Josse Robert G , Leiter Lawrence A , Kendall Cyril WC , Sievenpiper John L , Jenkins David JA
Published: November 2023

Background

Hypertension is associated with increased risk for cardiovascular disease and various vascular complications. Nutritional intervention, including specific dietary patterns and individual foods, plays a large role in the prevention and management of hypertension. We have previously shown that a low glycemic index (GI) diet with a principal focus on pulses resulted in significant reduction in blood pressure (BP). We therefore decided to assess whether this was a general pulse effect and so looked at a further trial where pulses were only one of many foods emphasized to lower the dietary GI.

Objective

To investigate the effect of dietary pulse consumption on blood pressure in individuals with type 2 diabetes mellitus (T2DM).

Methods

A secondary analysis was performed of data collected from a 6‐month randomized controlled trial conducted in 124 men and postmenopausal women with T2DM. Subjects had been randomized to either a high cereal fiber control diet or a low GI test diet which included recommendations for pulses. Dietary data from weighed 7‐day food records, anthropometric and BP measurements were collected for each month. The effect of pulse consumption on monthly systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP) was analyzed using a repeated measures analysis (PROC MIXED in SAS 9.3).

Results

Consumption of dietary pulses resulted in a reduction of 1.42mmHg in SBP (p = 0.0417), 1.07mmHg in DBP (p = 0.0170), and 1.18mmHg in MAP (p = 0.0155) for every 100 kcal (approximately 1/3–1/2 cup) of dietary pulses included as part of the daily diet. The effect of pulse consumption was consistent over time, with no significant pulse*time interaction. Independent and collective adjustments for age, sex, change from baseline energy intake and change from baseline sodium intake did not alter significant reductions seen for all three blood pressure measurements. Further adjustments for change from baseline BMI, medication use, or potassium intake each resulted in marginal loss of significance for SBP and/or DBP, but maintained significance for MAP, while adjustment for GI resulted in loss of significance for all three BP measures.

Conclusions

Increasing intake of dietary pulses decreased blood pressure in a sample of individuals with T2DM. GI may be a possible causal pathway by which pulses affect blood pressure.

Support or Funding Information

Canadian Institutes of Health Research, Loblaw Brands Limited, Barilla
Navy Bean Supplementation in Obesity Increases Akkermansia muciniphila Abundance and Attenuates Obesity Related Impairments in Gut Barrier Function
Authors: Monk Jennifer M , Lepp Dion , Wu Wenqing , Graf Daniela , Hutchinson Amber L , Robinson Lindsay E , Power Krista A
Published: November 2023

Fiber‐rich dietary pulses, such as common beans (Phaseolus vulgaris) have the potential to modify the colonic microenvironment (microbiota and host epithelial barrier) which can mitigate the severity of gut‐associated pathologies. Obesity is associated with impairments in the mucosal barrier (leaky gut) and specific changes in the abundance of bacteria communities within the gut microbiota. The objective was to assess the gut health promoting effects of 20% cooked navy bean flour supplementation in both the lean healthy and obese states. Two studies were conducted wherein male C57BL/6 mice were fed either a low fat control (LF, 10% fat as kcal) or an isocaloric bean supplemented diet (LF+B) for 3 weeks (Study 1: lean healthy), or a high fat diet (HF, 60% fat as kcal) or isocaloric bean supplemented (HF+B) diet for 12 weeks (Study 2: diet induced obesity). In lean mice, using fecal 16S rRNA sequencing, LF+B altered the abundance of critical gut microbial families including increased abundance of S24–7 (1.5‐fold) and Prevotellaceae (71‐fold) and decreased abundance of Peptococcaceae (3.7‐fold), Streptococcaceae (8.4‐fold), Clostridiaceae (12‐fold), Rikenellaceae (2.5‐fold) and Porphyromonadaceae (2.5‐fold) versus LF. These changes were associated with increased microbial activity (i.e, short chain fatty acid (SCFA) production) and colonic tissue expression of the SCFA receptors GPR41, 43 and 109a. LF+B improved gut barrier integrity and function by increasing i) mucus production, ii) anti‐microbial defenses, iii) tight junction protein expression, and iv) reducing serum lipopolysaccharide levels. These beneficial effects were sustained in obesity wherein HF+B fed mice exhibited improvements in both gut microbiota activity and community structure and aspects of the obese phenotype. Specifically, fecal abundance of Akkermansia muciniphila, whose abundance is inversely related to the severity of the obese phenotype, was increased in the HF+B group versus HF by 20‐fold, which was associated with a reduction in visceral adipose mRNA expression of the inflammatory mediators MCP‐1 and IL‐6 and increased expression of adiponectin. Colon epithelial barrier integrity was improved in the HF+B group versus HF, as evidenced by increased mRNA expression of tight junction components (ZO‐1, occludin, JAM‐A and claudin‐2) and functionally by reduced serum FITC‐dextran concentration in an in vivo gut permeability test. Additionally, evidence of an enhanced mucus barrier and anti‐microbial defence was apparent in the HF+B group versus HF based on increased goblet cell number and upregulated expression of Muc1‐3 and Reg3γ, respectively. In conclusion, bean supplementation enhanced gut barrier integrity and exerted a beneficial colon‐function priming effect that helps mitigate the severity of the obese phenotype.

Support or Funding Information

ORF, AAFC Pulse‐Cluster
Studies of Cream Seeded Carioca Beans (Phaseolus vulgaris L.) from a Rwandan Efficacy Trial: In Vitro and In Vivo (including effects on intestinal microbiome) Screening Tools Reflect Human Studies and Predict Beneficial Results from Iron Biofortified Beans
Authors: Tako Elad , Glahn Raymond P
Published: November 2023

Iron (Fe) deficiency is a highly prevalent micronutrient insufficiency predominantly caused by a lack of bioavailable Fe from the diet. The consumption of beans as a major food crop in some populations suffering from Fe deficiency is relatively high. Therefore, our objective was to determine whether a biofortified variety of cream seeded carioca bean (Phaseolus vulgaris L.) could provide more bioavailable‐Fe than a standard variety using in‐vivo (broiler chicken, Gallus gallus) and in‐vitro (Caco‐2 cell) models. Studies were conducted under conditions designed to mimic the actual human feeding protocol. Two carioca‐beans, a standard (G4825; 58μg Fe/g) and a biofortified (SMC; 106μg Fe/g), were utilized. Diets were formulated to meet the nutrient requirements of Gallus gallus except for Fe (33.7 and 48.7μg Fe/g, standard and biofortified diets, respectively). In‐vitro observations indicated that more bioavailable‐ Fe was present in the biofortified beans and diet (P<0.05). In‐vivo, improvements in Fe‐status were observed in the biofortified bean treatment, as indicated by the increased total‐body‐Hemoglobin‐Fe, and hepatic Fe‐concentration (P<0.05). Also, DMT‐1 mRNA expression was increased in the standard bean treatment (P<0.05), indicating an upregulation of absorption to compensate for less bioavailable‐ Fe. These results demonstrate that the biofortified beans provided more bioavailable Fe; however, the in vitro results revealed that ferritin formation values were relatively low. Such observations are indicative of the presence of high levels of polyphenols and phytate that inhibit Fe absorption. Indeed, we identified higher levels of phytate and quercetin 3–glucoside in the Fe biofortified bean variety. Our results indicate that the biofortified bean line was able to moderately improve Fe‐status, and that concurrent increase in the concentration of phytate and polyphenols in beans may limit the benefit of increased Fe‐concentration. Therefore, specific targeting of such compounds during the breeding process may yield improved dietary Fe‐bioavailability. Our findings are in agreement with the human efficacy trial that demonstrated that the biofortified carioca beans improved the Fe‐status of Rwandan women. We suggest the utilization of these in vitro and in vivo screening tools to guide studies aimed to develop and evaluate biofortified staple food crops. This approach has the potential to more effectively utilize research funds and provides a means to monitor the nutritional quality of the Fe‐biofortified crops once released to farmers. In addition, cecal contents analysis indicated that the lower Fe status in the standard bean treatment group had altered the composition, structure and function of the intestinal microbiome.
The Effect of a Low‐Glycemic Index Pulse‐Based Diet on Performance and Body Composition in Soccer Players
Authors: Mizelman Eliran , Chilibeck Philip , Hanifi Abdullah , Kaviani Mojtaba , Brenna Eric , Zello Gordon
Published: November 2023

Low‐glycemic index foods, such as pulses (i.e. lentils, peas, chickpeas, beans), have potential to improve endurance exercise performance because they do not induce a large release of insulin; this allows greater fat oxidation and preservation of muscle glycogen during endurance exercise. In addition to containing low‐glycemic index carbohydrate, pulses are a good source of protein and contain low levels of fat; therefore, they have potential to improve body composition. The objective of our study was to determine the effect of a one‐month pulse‐based diet on endurance performance and body composition in soccer players. Seventeen soccer players (11 females) who were university or city‐league players were randomized to consume their regular diet or were given a pulse‐based diet (i.e. 25% of daily caloric intake, as calculated from 3‐d food logs, was given as pulses, including beans, lentils, chickpeas, or peas) for one month, followed by a wash‐out of 2 weeks, and then the opposite diet for another month. Before and after each one‐month phase body composition was assessed by dual energy X‐ray absorptiometry. During each diet phase soccer performance was assessed as distance the players were able to cover during games by a global positioning system (Catapult Sports Optimeye X5). An hour before each game, players consumed 1.0 g available carbohydrate per kg of body mass, from either a pulse‐based sport nutrition bar (i.e. during the pulse‐diet phase) or a commercially‐available high‐glycemic index sport nutrition bar (i.e. during the regular diet phase). Distance covered during games was analyzed by magnitude‐based inferences, assuming a smallest substantial change in distance of 102 meters, based on game‐to‐game variability in distance covered.

Results

Male soccer players significantly decreased percent body fat during the pulse‐based diet phase (14.3 SD 2.2 to 13.4 SD 2.2%) compared to the regular‐diet phase (13.7 SD 2.1 to 14.1 SD 2.2%) (p=0.01); whereas, change in percent body fat was not different for females between the two diet phases (i.e. 24.5 SD 3.4 to 23.2 SD 4.3% during the pulse diet phase vs. 24.0 SD 3.8 to 23.1 SD 4.6% during the regular diet phase). During the pulse diet phase the soccer players covered an average of 9590 SD 1450 m during 90‐minutes of match time compared to 9360 SD 1471 m during the regular diet phase. The mean difference in distance covered between the pulse diet and regular diet phase (230 m, 90% CI −206 to 667 m) represents a 70% chance that the pulse diet was superior to the regular diet for increasing distance covered per game. We conclude that a pulse‐based diet improves body composition in male, but not female soccer players and that a pulse‐based diet may allow players to run a greater distance during soccer matches.

Support or Funding Information

Supported by the Saskatchewan Pulse Growers and the Western Grains Research Foundation
Are Chromium (Cr) Supplements Efficacious for Glycemic Control in Type 2 Diabetes (T2DM)?
Authors: Dwyer Johanna T , Costello R B , Bailey RL , Wambogo E
Published: November 2023

Chromium (Cr)‐containing dietary supplements are claimed to improve glycemic control in T2DM. We conducted a systematic literature search of randomized clinical trials (RCT) of adults with T2DM to document changes in glycemic control from pre‐ to post‐supplementation with Cr. The search included studies from 1/1991–1/2014 with the following terms: blood glucose, blood sugar, glucose metabolism disorders, or metabolic syndrome; randomized clinical trial, systematic review or meta‐analysis; trials with adults (>18yr.); T2DM defined by self‐report, clinical diagnosis or biochemical determination of elevated fasting plasma glucose [FPG ] or hemoglobin A1c [HbA1c];with and without concurrent treatment with hypoglycemic agents; and RCT design having a placebo or comparator control along with the Cr dietary supplement. Exclusions were studies in children, or solely in patients with T1DM; presence of unstable chronic disease and/or acute conditions; studies of combination therapies without a separate Cr supplement; observational, non‐randomized or un‐blinded studies; and those not reporting results pre vs. post‐supplementation. We defined elevated FPG as >126 mg/dL, or elevatedHbA1c as > 6.5%, and treatment goals as FPG ≤ 130 mg/dL, or ≤7.0% HbA1c, and a clinically substantial decrease as ≥0.5% HbA1c (or 60 mg/dL, a criterion based on reduction achieved by successful drug therapy; no similar criterion was available for a single FPG). A total of 20 RCT (22 arms) were identified. Many different doses and forms of Cr were used. 16 of 20 RCT continued hypoglycemic medications and lifestyle modifications during Cr supplementation, which confounded the interpretation of the cause of changes during supplementation. Many studies failed to show decreases compared to controls and in others decreases were small. Glycemic treatment goals were reached after Cr supplementation in 5/20studies using the mean FPG criterion, 3/14 using HgA1c, and 1/14 using both FPG and HgA1c. Mean HbA1c declined by ≥0.5% in 5/14 RCT, but in 4/5 of those with a drop concurrent hypoglycemic medications were also administered. Neither dose nor duration of Cr supplementation appeared to be associated with effectiveness. Also, we discovered that many of the RCT had features that threatened their quality, including heterogeneous study populations, small study size, high drop‐out rates, and short study duration. Moreover, in many studies the advantages of randomization for causal inference were lost due to high dropout rates and analyses solely of completers (per protocol analysis) rather than by intent to treat. The low strength of the evidence to date makes it unlikely that Cr supplements are efficacious for glycemic control. Future meta‐analyses should be selective and use similar inclusion criteria, similar forms of Cr, and include only high quality studies to provide scientifically sound recommendations.

Support or Funding Information

Funding: Office of Dietary Supplements, National Institutes of Health.
Inclusion of 100% Concord grape juice reduces glucose release following in vitro digestion of a model carbohydrate rich meal
Authors: Moser Sydney Elizabeth , Lim Jongbin , Whiteman J. D. , Hamaker Bruce , Ferruzzi Mario
Published: November 2023

Growing evidence suggest that phenolics from fruits and juices including 100% grape juice (GJ) may impact glucose homeostasis by independently inhibiting carbohydrate digestion and modulating intestinal glucose transport. However, the extent to which these effects are extendable to 100% GJ in the context of interaction within a meal remains unclear. To determine the influence of 100% GJ from purple American grapes (V. labrusca; Concord) on starch digestion and intestinal glucose release from a meal, GJ was combined (5 and 10% w/w) with a milk and cornstarch‐based pudding (MSP) providing protein and complex carbohydrates simulating a meal. This combination was introduced to an in vitro digestion model mimicking oral, gastric and small intestinal digestion. Phenolic bioaccessibility and extent of glucose release from starch were assessed following digestion. Concord GJ is rich in phenolic acids and flavonoids (806 to 845 μM total phenolics) including catechin, quercetin and isorhameritin, as well as anthocyanins (80 to 103 μM total anthocyanins) with cyanidin and delphinidin most abundant. Co‐digestion of GJ with MSP did not significantly impact bioaccessibility of total phenolics suggesting the food matrix did not impact digestive stability and ultimate bioaccessibility in the GI tract. Total glucose content in final digesta was decreased by 12% following co‐digestion of MSP with 10% Concord GJ (~55 μM phenolics) compared to sugar match control. No significant effect was observed from 5% Concord GJ. GJ phenolic extracts also demonstrated modest inhibition of a‐amylase at 500 μM phenolics (3.4–8.8%) and of glucoamylase activity at 300 and 500 μM phenolics (4.9 and 9.3%, respectively). Combined these data suggest that consumption of 100% GJ, compared to a sugar sweetened beverage, with a carbohydrate‐rich meal may delay digestive release of glucose in the upper GI through inhibition of glucoamylase leading to a modest reduction in glycemic response from a meal.

Support or Funding Information

Funding support by Welch Foods
Effect of Decaffeinated Green and Black Tea Extracts on Energy Metabolism in Mice Fed a High Fat/High Sucrose/Western Diet
Authors: Henning Susanne M , Yang Jieping , Grojean Emma M , Lee Ru‐Po , Hsu Mark , Heber David , Li Zhaoping
Published: November 2023

Although green tea (GT) and black tea (BT) are chemically very different, both reduce body weight and fat depots in male C57BL/6J mice fed a high‐fat/high‐sucrose (HF/HS) diet. A portion of GT polyphenols is absorbed in the small intestine while the majority of high molecular weight polyphenols from BT reach the large intestine. In the colon all tea polyphenols are converted to smaller phenolic compounds by the microflora. We have demonstrated that GT and BT dramatically change the composition of the intestinal microflora. It is the objective of the present study to determine intestinal and hepatic targets of tea polyphenols contributing to the anti‐obesogenic activity of GT and BT.

48 C57BL/6 male mice were randomly assigned to one of four treatment groups: control HF/HS (Western) diet (32% kcal from butter fat and corn oil, 25% kcal from sucrose), or a HF/HS‐diet supplemented with either GT or BT extract providing 0.25% polyphenols, or a low fat diet (10.6% kcal from fat) for 4 weeks. All observations are in comparison to the HF/HS‐diet fed control mice. GT and BT administration decreased body weight, epidydimal, mesenteric and subcutaneous fat as determined by weight. Only BT significantly increased propionic acid and i‐butyric acid in the cecum as determined by gas chromatography. Real‐time quantitative PCR demonstrated that GT and BT decreased gene expression of fatty acid transporters in ileum tissue of fatty acid binding protein 2 (Fabp2) significantly and BT induced a trend to decrease gene expression of fatty acid binding protein 4 (Fatp4) and cluster of differentiation/fatty acid translocase (Cd36/Fat). Gene expression of the following hepatic key regulatory enzymes of fatty acid β‐oxidation was increased significantly by GT: 1) Carnitine palmitoyl transferase 1 and 2 (Cpt1a, Cpt1b, Cpt2), that regulate transport of cytosolic fatty acids to mitochondria and 2) long chain and very long chain acetyl CoA dehydrogenase (Lcad, VLcad), that catalyze the first step in FA β‐oxidation in the mitochondria. In the liver of mice consuming the HF/HS‐BT diet AMPK protein phosphorylation was increased significantly as determined by Western blot.

In summary, the anti‐obesity effects of GT and BT were induced through different mechanisms. Only GT stimulated liver energy expenditure directly, while BT increased SCFA formation significantly leading to stimulation of AMPK phosphorylation and both teas reduced intestinal fatty acid transport.

Support or Funding Information

Supported by NIH RO3CA171583 and departmental funds of the Center for Human Nutrition Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles
Cocoa Increases Postprandial GLP‐1 Response in Adults with Impaired Glucose Tolerance
Authors: Strat Karen , Davy Brenda M , Hulver Matthew W , Davy Kevin P , Neilson Andrew Peter
Published: November 2023

Prediabetes (elevated fasting glucose or impaired glucose tolerance) is an intermediate state in the development of type‐2 diabetes. Strategies are needed to prevent progression from this “at‐risk” state to fully developed disease. Cocoa flavanols offer a unique potential solution to improve glucose homeostasis by inhibiting digestive enzymes and stimulating an incretin hormone response. The purpose of this study was to determine the effects of acute cocoa consumption on postprandial blood glucose, insulin, and incretin hormone levels following a mixed meal in adults. Sixteen adults at risk for developing type‐2 diabetes were enrolled: n=11 had normal glucose tolerance (NGT, blood glucose < 140 mg/dl 2 h after 75 g OGTT) and n=5 had impaired glucose tolerance (IGT, 140–199 mg/dl 2 h after OGTT). Subjects completed two meal challenges consisting of a meal replacement shake blended with a cocoa beverage powder (10 g cocoa) or placebo beverage powder (0 g cocoa) in a randomized crossover design. Intravenous blood samples were taken at baseline and over 4 h post‐meal. For all subjects pooled together, cocoa significantly increased postprandial C‐peptide excursion from baseline compared to placebo (p = 0.0463). When data were split by phenotype (NGT vs. IGT subjects), the IGT cohort had slightly (but not significantly) lower fasting GLP‐1 levels and postprandial GLP‐1 response compared to the NGT cohort. Furthermore, the IGT cohort had significantly increased maximum postprandial GLP‐1 levels (p = 0.0452) with cocoa vs. placebo. In IGT subjects, GLP‐1 area under the curve and excursion from baseline approached significance with cocoa vs. placebo (p = 0.0759 and p = 0.0642, respectively). There were no differences in GLP‐1 response between treatments for the NGT group. There were no effects of cocoa on glucose, insulin, GIP, or adiponectin for either cohort or pooled subjects. Our data suggest that natural cocoa may rescue an impaired GLP‐1 response seen in adults with impaired glucose tolerance; NGT individuals may not experience these improvements, as their incretin and glycemic responses are not impaired. In conclusion, natural cocoa may be helpful in maintaining glucose homeostasis by enhancing the incretin response in a subset of adults at risk of developing type‐2 diabetes.

Support or Funding Information

Funding was provided by The Hershey Co., Hershey, PA.
The Hypoglycaemic Potential of Antioxidant‐Rich Food Extracts
Authors: Chepulis Lynne
Published: November 2023

Background/Aims

Prediabetes and Type 2 diabetes are highly prevalent in the USA as well as Western countries, and both conditions are associated with impaired glucose control. Research suggests that low GI diets and reduced HbA1c values can be one means by which disease progression can be slowed, and antioxidants have been identified as having the ability to regulate plasma glucose levels. The aim of this study is to assess the effects of specific high‐antioxidant food extracts on postprandial glucose responses to sugar (glucose) and a basic carbohydrate meal.

Methods

Ten healthy individuals were recruited into a randomized, single‐blinded study. Participants were asked to consume various high‐antioxidant food extracts that were matched for total antioxidant content 10 mins prior to 50g of available carbohydrate from either glucose or white bread (with ham) after an overnight fast. Blood glucose levels were measured using capillary sampling every 15 mins for two hours, and the incremental area under the glucose curve (IAUC) measured. The IAUC values for the test food extracts were compared to the glucose‐only and bread/ham‐only controls.

Results

Amla berry‐, Grape seed‐ Rooibos tea‐ and Green tea‐ extracts as well as Propolis tincture were all strong glycemic modulators, significantly decreasing the IAUC by 25–39% compared to the glucose‐only or bread‐only controls (all p < 0.05). All extracts were well tolerated, and no more than one gram of extract was required to achieve the aforementioned results.

Conclusions

Antioxidant‐rich food extracts are able to reduce the postprandial response of glucose and white bread with ham; thus they may offer a potential means by which glycemic control could be managed in individuals who have impaired glucose control.

Support or Funding Information

This study was funded by in part by Manuka Health New Zealand Ltd, and in part by Waiairki Institute of Technology, New Zealand
Ingested Capsaicinoids Can Prevent Low‐Fat/High‐Carbohydrate diet and High‐Fat Diet‐Induced Obesity by Regulating the Expression of Genes for Metabolism
Authors: Sahin Kazim , Orhan Cemal , Tuzcu Mehmet , Sahin Nurhan , Ozdemir Oguzhan , Juturu Vijaya
Published: November 2023

BACKGROUND

We previously found that ingested capsaicinoids (CAPs) inhibit pancreatic lipase and the mRNA levels of adipogenic genes such as peroxisome proliferator‐activated receptor‐gamma (PPAR‐gamma) and CCAAT enhancer‐binding protein‐alpha (C/EBP‐alpha) decreased in in vitro models. The aim of this study was to investigate the capsaicinoids (CAPs) effects on regulating the gene protein levels in low fat/high carbohydrate diet (LF/HCD) and high fat diet (HFD) induced obesity in rats.

METHODS

Eight week male Wistar rats were fed on a LF/HCD and HFD with and without capsaicinoids compared with control group (CTL, +/− CAPs) for 8 weeks to induce obesity. Subsequently they were divided into different groups and were maintained on a CTL (+/− 0.2mg CAPs, 10 mg/kg bw CapsimaxTM, LF/HCD (+/− 0.2mg CAPs, 10 mg/kg bw CapsimaxTM) and HFD (+/−0.2 mg CAPs, 10 mg/kg bw CapsimaxTM) for 8 weeks. Changes in the gene protein levels of gp91phox (NOX2), Sirtuin 1 (SIRT1), nuclear factor NF‐κB, endothelial NO synthase (eNOS), NFkB, p22phox Protein (CYBA) and nuclear factor erythroid 2–related factor 2 (Nrf2) were analyzed. Serum and liver TBARS and total antioxidant capacity (TAC) were analyzed in all treatments.

RESULTS

Experimental diets supplemented with CAPs lowered the levels of mRNA levels of gp91phox (NOX2), NFkB, p22phox Protein (CYBA) and However, the mRNA levels of SIRT an important regulator of energy metabolism, Nrf2 an emerging regulator of cellular resistance to oxidant, eNOS a vasoprotective molecule nitric oxide (NO·) were significantly increased. CAPs treated groups had significant decrease in TBARS in serum and liver tissue and an increase in serum TAC were observed.

CONCLUSION

These results suggest that CAPs effectively reduces TBARS and increased TAC. These effects might be at least partially mediated via regulation of the gene proteins involved in energy metabolism, oxidative stress and vasoprotection.

Support or Funding Information

OmniActive Health Technologies Inc.
Depletion of Programmed Cell Death Protein 4 (PDCD4), an mTORC1/S6K1 Substrate, Attenuates Proteolysis in L6 Myotubes
Authors: Adegoke Olasunkanmi John , Sawan Sidney Abou , Cho Hankyul
Published: November 2023

The mammalian (mechanistic) target of rapamycin complex 1/ribosomal S6 Protein kinase 1 (mTORC1/S6K1) signaling pathway is a critical regulator of skeletal muscle protein synthesis and mass. Because mTORC1 signaling is also implicated in autophagy control, regulation of muscle protein mass by mTORC1 may be mediated by regulation of protein synthesis and/or degradation. We recently characterized the expression of programmed cell death protein 4 (PDCD4), a substrate of mTORC1/S6K1, in skeletal muscle. This pro apoptotic protein normally inhibits mRNA translation by binding to eukaryotic translation initiation factor 4A (eIF4A), but upon phosphorylation by S6K1, it is targeted for proteolysis by the ubiquitin dependent proteolytic system. Depletion of PDCD4 in myoblasts attenuated the suppression of protein synthesis that is normally observed in response to amino acid starvation. Surprisingly in myotubes, PDCD4 depletion led to a reduction in protein synthesis. This led us to hypothesize that PDCD4 likely regulates both protein synthesis and degradation, and that its depletion would lead to a greater suppression of proteolysis (compared to suppression of protein synthesis), thus leading to positive protein balance. L6 myotubes were depleted of PDCD4 by RNA interference. Thirty‐six hours later, cells were pulsed with S‐35 methionine/cysteine for 12 hours. To activate proteolysis, cells were then incubated either in amino acid‐free medium (starvation), or in 1 μM dexamethasone for varying lengths of time. Samples were then harvested and subjected to autoradiography to measure residual radioactivity. At 24–36 hours, starvation increased the disappearance of radiolabeled protein by 50–80% compared with non‐starved cells (P<0.05), consistent with increased proteolysis. In PDCD4 depleted cells, starvation‐induced proteolysis was suppressed by 40–60% (P<0.05). Ubiquitinated proteins accumulated to a greater extent (40–100%) in starved PDCD4‐depleted cells compared to cells treated with control siRNA (P<0.05), consistent with inhibition of degradation of ubiquitinated proteins. In dexamethasone treated cells, proteolysis was inhibited by ~20% in PDCD4 depleted cells compared to cells treated with control siRNA (P<0.001). These data are consistent with a role for PDCD4 in regulating not only protein synthesis but also proteolysis. Therefore, interventions that target PDCD4 may help in limiting muscle proteolysis seen in catabolic conditions like cancer and insulin resistance states.

Support or Funding Information

NSERC; York University
Lipoprotein Lipase Modulates Bone Marrow Myeloid Cell Proliferation by Affecting Colony‐Stimulating Factor Levels and Recruitment
Authors: Chang Chuchun Liz , Goldberg Ira J , Deckelbaum Richard J
Published: November 2023

Although inflammation is the body's basic response to ameliorate injury or infection, tissue macrophage‐mediated pro‐inflammatory responses promote metabolic diseases, such as atherosclerosis. Lipoprotein lipase (LpL) is the rate‐limiting enzyme that hydrolyzes circulating lipoprotein triglycerides (TG) to release free fatty acids. We have reported that loss of LpL expression reduced numbers of aortic macrophages and bone marrow (BM) myelopoiesis. Reconstitution of LpL‐expressing BM was able to replenish aortic macrophage density. Our current studies are directed toward understanding the molecular regulation of LpL in orchestrating lipoprotein metabolism and immune cell biology. Our data show that reduced aortic macrophage levels were associated with reduced blood white cells and leukocyte subsets, including macrophage precursor cells‐ monocytes. BM‐derived monocyte differentiation to macrophages was markedly reduced by 40% in the absence of LpL (p<0.05). We speculate that defective lipid metabolism induced by LpL deficiency can contribute to decreased BM myelopoiesis. In transgenic LpL knockout mice that are rescued from neonatal death by muscle‐specific LpL expression (MCKL0 mice), loss of LpL reduced BM monocyte/macrophage precursor (BMMP) cell TG uptake and accumulation by 22% and 50% (p<0.05), respectively. TG utilization was much lower (~40%) in MCKL0 BMMP cells compared to wild type (WT) BMMP cells. LpL deficiency significantly decreased BM expression of both macrophage‐colony‐stimulating factor (M‐CSF) and its receptor (M‐CSF‐R), required for myeloid cell proliferation and differentiation (p<0.05). LpL‐mediated lipolysis products (e.g., oleic acid) were able to stimulate expression of M‐CSF and M‐CSF‐R by > 35% (p<0.05) in WT BMMP cells. In addition, LpL and heparin, which releases LpL from the cell surface, modulated binding of M‐CSF to M‐CSF‐R in the immunobinding assay (p<0.05). We hypothesize that LpL also anchors M‐CSF to its receptor and triggers a series of downstream signaling pathways to stimulate monocyte differentiation to macrophages. We thus propose that LpL, in addition to being a lipolytic enzyme, also influences peripheral and BM immune cell responses. These studies provide valuable insight into the regulation of adverse inflammatory responses and have therapeutic applications for various blood cell diseases.
A Plasma Proteome is Associated with Anthropometric Status in School‐aged Children in Nepal
Authors: Lee Sun Eun , Christian Parul , Schulze Kerry , Cole Robert N. , Wu Lee S. F. , Yager James D. , Groopman John , Stewart Christine P. , West Keith P.
Published: November 2023

Background

Child undernutrition, often interpreted as protein‐energy malnutrition (PEM), is typically assessed by anthropometry. Rarely are plasma markers of PEM considered in population surveys, masking opportunities to study biological mechanisms of poor growth.

Objective

This study aimed to identify plasma protein biomarkers associated with childhood body size measures and indicators of stunting, wasting, underweight and body composition using proteomics.

Methods

We correlated the relative abundance of plasma proteins quantified by mass spectrometry with measures of height, weight, mid‐upper arm circumference (MUAC), triceps skinfold thickness (TSF), and subscapular skinfold thickness (SSF), and estimated differences in relative abundance of proteins by stunting, underweight, and wasting status in 500 children 6–8 yr of age in rural Nepal.

Results

Among 982 proteins observed in >10% of all child plasma samples, we identified 18, 58, and 28 proteins associated with height‐for‐age Z‐scores (HAZ), weight‐for‐age Z‐scores (WAZ), and MUAC, respectively, passing a false discovery threshold of 10% (q<0.10). Fifteen proteins mainly involved in cell proliferation/differentiation, ossification, and host defenses were commonly associated with both HAZ and WAZ, whereas WAZ was also associated with extracellular matrix proteins. Three proteins involved in muscle contraction and maintaining the integrity of connective tissues were associated with BMI‐for‐age Z‐scores (BMIZ) and one protein, collagen (type 6) alpha1, was positively associated with arm fat area. Four proteins, including breast cancer type 2 susceptibility protein and sex hormone binding protein, were associated with SSF and no proteins were associated with TSF (q<0.10). Twelve proteins including insulin‐like growth factor‐1 (IGF‐1), IGF‐binding proteins (IGFALS and IGFBP3), and tetranectin were 3–15% less abundant in the plasma of stunted children (HAZ<−2) relative to non‐stunted children (q<0.10). Fifteen proteins, including IGF‐1, ‐2, ‐ALS, and ‐BP3 and others involved in angiogenesis, nutrient transport, and nervous system development were 3–24% less abundant while 3 proteins related to regulation of adipogenesis and neuroendocrine secretory function were 7–9% more abundant in underweight children (WAZ<−2) than non‐underweight children (q<0.10). No protein was differentially abundant by low BMI (BMIZ<−2) status.

Conclusions

Subsets of the plasma proteome correlated with body length, weight, lean mass and fat mass in school‐aged children. The utility of identified proteins as biomarkers of growth processes leading to underweight, stunting and altered body composition merits further investigation.

Support or Funding Information

This study is funded by the Bill and Melinda Gates Foundation (OPP5241 and GH614).
Maternal Docosahexaenoic Acid (DHA) Supplementation Promotes Lean Body Mass in the Preterm Infant
Authors: Valentine Christina J. , Kleiman Jeanne , Dingess Kelly , Morrow Adrythe , Rogers Lynette K
Published: November 2023

Background

Maternal supplementation with 1000 mg/day docosahexaenoic acid (DHA) increases breast milk concentration to target fetal third trimester DHA accretion levels. Recent studies have observed correlations between n‐3 LCPUFA levels and lean body mass. Given that extremely preterm infants experience rapid “catch‐up” growth after birth, sufficient quantities of DHA in breast milk may decrease fat accumulation and increase lean mass in this population.

Methods

Mother/infant dyads were enrolled at the time of birth and randomized to receive 200 or 1000 mg/day of single source (algeal) DHA for 8 weeks. Inclusion criteria was that the infants be born <28 weeks gestation and have no congenital anomalies. A total of 18 mother infant dyads completed the study, 8 on 200 mg/day and 10 on 1000 mg/day DHA supplementation. Body composition was assessed by PEA POD®, utilizing air displacement plethysmography and whole body densitometry, at term corrected gestational age or hospital discharge. Data were analyzed by Multivariate General Linear Regression using DHA supplementation as the primary variable and age at analysis as a co‐variant.

Results

Comparing infants fed by mothers receiving 200 mg vs 1000 mg DHA per day, data indicated lower percent fat (12.4 vs 11.0, p=0.030); fat mass (0.38 vs 0.33, p=0.014); body mass (3.00 vs 2.90 kg, p=0.042); and body volume (2.91 vs 2.81 L, p=0.039); and higher percent fat free mass (87.6 vs 89.0, p=0.030). No differences were observed in overall length.

Conclusions

The total number of infants in this study is small but we observed decreases in parameters of body fat and body mass and increases in percent fat free mass in the infants nursed by mothers supplemented with 1000 g/day DHA. Larger studies are needed to determine if higher levels of dietary DHA regulates excess fat accumulation in this population of extremely preterm infants.

Support or Funding Information

This work was supported by the National Institutes of Health, NCCIH/ODS (LKR R01AT006880).
Does the left hand know what the right hand is doing? Part II: Alignment between the AFRI Childhood Obesity Prevention Challenge Area Program and the 2010 Dietary Guidelines
Authors: Koenings Mallory Marie , Perez Crystal , Krishnan Kavitha , Chester Deirdra N
Published: November 2023

Funding integrated research projects is essential to address the health of our nation's children and decrease the burden of preventable diseases. In response in 2010, USDA's Agriculture and Food Research Initiative (AFRI) Childhood Obesity Prevention Challenge Area was established. The Childhood Obesity Prevention (COP) Challenge Area program funds integrated projects; models of optimal collaboration between research, education and Extension agricultural knowledge systems. This study examined the alignment between funded projects in COP and the five major concepts of the 2010 Dietary Guidelines for Americans (2010 DGA); Balancing Calories to Manage Weight, Foods and Food Components to Reduce, Foods and Nutrients to Increase, Building Healthy Eating Patterns, and Helping Americans Make Healthy Choices. Thetopic modeling tool PushGraph compared the text of the 2010 DGA and project proposals from the COP program area. Results were limited to funded projects with at least 10% similarity to the 2010 DGA and proposals received after 1 January2011. A total of 29 COP projects, in whole $66,887,383 were identified. All(100%) eligible projects had ≥15% similarity to the 2010 DGA. Meaning at least 15% of the project proposal discussed one of the five 2010 DGA topics. Two COP projects (7%) had 15% similarity, 14 (48%) had 16–20% content alignment, and for 13 (45%) projects more than 1/5 of the proposal discussed a 2010DGA concept. The majority, 10 (34%), of COP projects were Helping Americans MakeHealthy Choices. The least, 2 (7%), COPprojects related to Building HealthyEating Patterns, 3 (10%) integrated projects addressed Foods and Food Components to Reduce, 5 (17%) were aligned with Foods and Nutrients to Increase, and 9(31%) COP projects performed research, education, and Extension activities working toward Balancing Calories to ManageWeight. These 29 COP awards represent27 institutions ‐‐ two institutions received 2 awards. The majority of awards, 18 (62%), were made to1862 Land Grant Universities, 1 (3%) award was made to an 1890 Land Grant University, 5 (17%) awards were made to Non Land Grant Public Universities, and5 (17%) awards were made to private universities. Overall, the National Institute of Food and Agriculture, USDA Childhood Obesity Prevention Challenge Area program achieved strong alignment with the 2010 Dietary Guidelines for Americans. Future efforts continue to be made by NIFA to increase the representation of 1890 Land Grant Universities, 1994 Tribal Colleges, Minority and Hispanic Serving Institutions among awarded institutions. Continued utilization of topic modeling may not only facilitate alignment between the Childhood Obesity Prevention program and the 2015 Dietary Guidelines for Americans, but also enhance the coordinated efforts of federal agencies to improve our nation's health.