Dietary Dose Research Articles

Investigating the relationship between β-carotene intake from diet and supplements, smoking, and lung cancer risk

β-carotene is a naturally occurring and safe dietary source of vitamin A that is associated with cancer risk reductions when consumed in typical dietary amounts. However, two clinical trials reported increased incidence of lung cancer and total mortality among heavy smokers taking β-carotene supplements (20 or 30 mg/day). Based on these findings, the Joint FAO/WHO Expert Committee on Food Additives withdrew Acceptable Daily Intake values for β-carotene (0–5 mg/kg bw). We evaluated relevant epidemiological and toxicological literature to assess the biological plausibility of this relationship and identified three mechanisms involving cellular proliferation signaling, a mode of action for cancer promotion. The overall weight of evidence consistently demonstrated typical dietary doses of β-carotene decreased cellular proliferation signaling via these mechanisms, even in the presence of smoke, while co-exposure to smoke and higher, supplemental doses increased cellular proliferation signaling through these same pathways. The production of excessive oxidative β-carotene metabolites via reactions with smoke constituents may be a key event underlying this relationship. Consistent with previous findings, our evaluation indicated consumption of up to 50 mg/day β-carotene does not present safety concerns for the non-smoking general population. Heavy smokers consuming less than 15 mg β-carotene/day are not expected to be at an increased risk of lung cancer.

Dietary Malondialdehyde Impair Intestinal Health and Fillet Quality of Hybrid Grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂).

Aquafeed kept at elevated temperatures and humidity can result in malondialdehyde (MDA) formation, adversely affecting aquafeed quality and triggering negative reactions in fish. To investigate the detrimental effects of dietary MDA on fish, six experimental diets with varying MDA levels (ranging from 0.03 to 17.72 mg/kg, on dietary crude lipid basis) were administered to three replicates of hybrid grouper for 8 weeks. Dietary inclusion of 4.43 mg/kg MDA significantly decreased serum complement 4 content and lysozyme activity, along with intestinal complement 3, complement 4, and immunoglobulin M contents. Furthermore, dietary inclusion of 8.86 mg/kg MDA significantly increased the activities of interleukin-1 receptor-associated kinase, ubiquitin-protein ligase, p38 mitogen-activated protein kinase, and tumor necrosis factor-α, downregulated the relative expression of Occludin but upregulated the relative expression of HSP70 in the hindgut. Additionally, the highest inclusion of MDA (17.72 mg/kg) significantly upregulated the relative levels of pro-inflammatory cytokines (IL-1β and TNF-α), caused intestinal inflammation, and damaged the intestinal microbial structure and fish fillet texture. This study demonstrated a dose-dependent response of MDA on hybrid grouper. A low dietary dose of MDA (<2.21 mg/kg) exhibited minimal impact on immune response and fillet quality. However, higher inclusion levels (≥4.43 mg/kg) impaired the intestinal health and fillet quality. Consequently, the safety limit for MDA content in the diet for hybrid grouper has been established at 4.43 mg/kg based on dietary crude lipid basis.

New Insights on the Effects of Krill Oil Supplementation, a High-Fat Diet, and Aging on Hippocampal-Dependent Memory, Neuroinflammation, Synaptic Density, and Neurogenesis.

Krill oil (KO) has been described as having the potential to ameliorate the detrimental consequences of a high-fat diet (HFD) on the aging brain, though the magnitude and mechanism of this benefit is unclear. We thus hypothesized that dietary KO supplementation could counteract the effects of cognitive aging and an HFD on spatial learning, neuroinflammation, neurogenesis, and synaptic density in the cortex and hippocampus of aged rats. Sixteen-month-old Sprague Dawley rats were fed for 12 weeks while being divided into four groups: control (CON); control with KO supplementation (CONKO); high-fat diet (HF); and high-fat diet with KO supplementation (HFKO). We measured food consumption, body mass, spatial memory (Morris water maze), microglia, neurogenesis, cytokine concentrations, and synaptic markers (post-synaptic density-95 and synaptophysin). Predictably, an HFD did induce significant differences in body weights, with the high-fat groups gaining more weight than the low-fat controls. However, KO supplementation did not produce significant changes in the other quantified parameters. Our results demonstrate that the dietary KO dose provided in the current study does not benefit hippocampal or cortical functions in an aging model. Our results provide a benchmark for future dosing protocols that may eventually prove to be beneficial.

Identifying and modeling the impact of neonicotinoid exposure on honey bee colony profit

Abstract Pollination by the European honey bee, Apis mellifera, is essential for the production of many crops, including highbush blueberries (Vaccinum corymbosum). To understand the impact of agrochemicals (specifically, neonicotinoids, a class of synthetic, neurotoxic insecticides) on these pollinators, we conducted a field study during the blueberry blooms of 2020 and 2021 in British Columbia (B.C.). Forty experimental honey bee colonies were placed in the Fraser Valley: half of the colonies were located within 1.5 km of highbush blueberry fields (“near” colonies) and half were located more than 1.5 km away (“far” colonies). We calculated risk quotients for these compounds using their chronic lethal dietary dose (LDD50) and median lethal concentration (LC50). Pesticide risk was similar between colonies located near and far from blueberry forage, suggesting that toxicity risks are regionally ubiquitous. Two systemic neonicotinoid insecticides, clothianidin and thiamethoxam, were found at quantities that exceeded chronic international levels of concern. We developed a profit model for a pollinating beekeeper in B.C. that was parameterized by: detected pesticide levels; lethal and sublethal bee health; and economic data. For colonies exposed to neonicotinoid pesticides in and out of the blueberry forage radii, there were economic consequences from colony mortality and sublethal effects such as a loss of honey production and compromised colony health. Further, replacing dead colonies with local bees was more profitable than replacing them with imported packages, illustrating that beekeeping management selection of local options can have a positive effect on overall profit.

Impact of microplastics pollution on ciprofloxacin bioaccumulation in the edible mussel (Perna viridis): Implications for human gut health risks

Antibiotics and microplastics are prevalent pollutants in mariculture. Consuming contaminated bivalves can potentially endanger human health, but the impact of microplastics on antibiotics bioaccumulation in bivalves and the related health risks to consumer health risks is not fully understood. We obtained bivalves from a mariculture farm and set up exposure scenarios with ciprofloxacin (1 μg/L) alone, microplastics (0.6 mg/L) alone, or their combination on mussels for 2-weeks. We investigated ciprofloxacin accumulation and analyzed the effects of these pollutants on detoxification and intestinal microbiome changes. Furthermore, potential food safety hazards related to ingestion of antibiotic-tainted bivalves were also assessed. We found that the accumulation of the ciprofloxacin in bivalves was significantly aggravated by the presence of microplastics. There was a significant increase in the production of antioxidant substances in the host's haemolymph, and an enhanced synthesis of antioxidants by the predicted metabolic functions of the intestinal microbiome. Concomitantly, microplastics exacerbated intestinal dysfunction, with a reduction in beneficial Spirochaetes and an increase in pathogenic bacteria Treponema, which may lead to deterioration of detoxification in the host. Additionally, an assessment of human gut health risks was conducted on the residual ciprofloxacin in bivalves combined with human consumption habits. The estimated target hazard quotients and cancer risk were below safety thresholds, directly consuming contaminated bivalves poses little toxicity. However, with raw mussels consumption, the dietary exposure doses of ciprofloxacin to human gut microbiome exceeded minimal selective concentrations for resistance. This could promote the growth of potentially resistant bacteria, indicating a risk of antibiotic resistance.

Nutrition and health effects of pectin: A systematic scoping review of human intervention studies.

Pectin is composed of a group of complex polysaccharides that are naturally found in various plants and are associated with a range of beneficial health effects. Health outcomes from dietary pectin can vary depending on botanical origin, dietary dose and structure of pectin. The objective of this scoping review is to build a comprehensive overview of the current evidence available on intervention studies conducted in humans and to better understand the possible knowledge gaps in terms of structure-function relationships across the different health-related effects. PubMed and Embase databases were searched using PRISMA-ScR guidelines, yielding 141 references (from the initial 3704), representing 134 intervention studies performed between 1961 and 2022 that met inclusion criteria. Studies were divided into six categories, which included gut health, glycaemic response and appetite, fat metabolism, bioavailability of micronutrients, immune response and other topics. Review of these human intervention studies identified a variety of cohort characteristics and populations (life stage, health status, country), sources/types of pectin (i.e. citrus, sugarbeet, apple, other and non-defined), intervention timeframes (from one single intake to 168 d) and doses (0.1-50 g/d) that were tested for health outcomes in people. Gut health, post-prandial glucose regulation and maintenance of blood cholesterol represented the largest categories of studied outcomes. Further research to strengthen the structure-function relationships for pectin with health properties and associated outcomes is warranted and will benefit from a more precise description of physico-chemical characteristics and molecular compositions, such as degree of esterification, weight, degree of branching, viscosity, gel formation and solubility.

Can TK-TD modelling bridge the gap between in vitro and in vivo mammalian toxicity data?

Repeated dietary dose testing is used to assess longer term toxicity of chemicals, such as pesticides, to mammals. However, the internal pesticide concentration varies significantly as feeding rate relative to body size fluctuates over time. Toxicokinetic-toxicodynamic (TK-TD) models can estimate internal toxicant concentration over time and link this directly to observed effects on endpoints such as the growth rate of laboratory rats. Using TK-TD models it is therefore possible to predict the effects that would result from a constant internal concentration of a pesticide. This presents the possibility of comparison with data from in vitro experiments, potentially facilitating quantitative in vitro to in vivo extrapolation (QIVIVE). We used in vivo TK-TD models to identify relevant internal concentrations and then estimated the experimental conditions required to replicate these in cultured cells, using in vitro TK models. Cell population growth was measured, with a view to extrapolating through time and comparing effect sizes with in vivo predictions. However, observed cell proliferation was not significantly affected by the tested concentrations of any of the five pesticides in this study and so extrapolation was not possible. In light of this negative result, we highlight areas for future work towards QIVIVE of graded sublethal effects in mammals. The most pressing objective is improving the accuracy of in vivo TK predictions, which could be achieved with dietary dosing in TK studies.

Combination of herbal extracts regulates growth performance, liver and intestinal morphology, antioxidant capacity, and intestinal microbiota in Acrossocheilus fasciatus

In the present study, the herbal extracts (RPTS) composed of Rheum palmatum: Schisandra sphenanthera: Terminalia chebula: Punica granatum with a weight ratio of 1.07: 3.00: 1.18: 1.38, was evaluated through a bacteriostatic assay in vitro. Afterwards, a 56-day feeding trial was operated to assess the impact of dietary RPTS at the dose of 0, 1.0, 2.5, 5.0, and 10 g·Kg−1 feed (entitled as Con, RPTS010, RPTS025, RPTS050, RPTS100 group, respectively) on the performance of Acrossocheilus fasciatus fingerlings. The results revealed that dietary RPTS at the dose of 2.5 g·Kg−1 feed remarkably improved the specific growth rate (SGR), and the gastrointestinal trypsin activity, as well as the catalase (CAT) activities, while slightly increased the alanine aminotransferase (ALT) activity and aspartate aminotransferase (AST) activity in the fish liver. Histological examination indicated that dietary high dose of RPTS (5.0 and 10.0 g·Kg−1 feed) could induce hepatic cell vacuolization and reduce the intestinal villi density of fish. Furthermore, the analysis of intestinal microbiota showed that Bacteroidota, Firmicutes and Proteobacteria were the three dominant phylum in all experimental groups, while the Firmicutes/Bacteroidota ratio exhibited a trend of initially decreasing followed by rising, with the supplementation level of RPTS increase. Additionally, the LEfSe analysis revealed that Cetobacterium was the most impacted species, which notably increased in RPTS025 group. Collectively, this study unveiled that the impact of dietary RPTS on fish performance was in a dose-dependent manner, and dietary RPTS at the dose of 2.5 g·Kg−1 feed could potentially enhance growth performance, digestive and antioxidant capacity, and positively modulate the intestinal microflora, without significantly impact liver health of A. fasciatus.

Ileum Proteomics Identifies Distinct Pathways Associated with Different Dietary Doses of Copper-Fructose Interactions: Implications for the Gut-Liver Axis and MASLD.

The interactions of different dietary doses of copper with fructose contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) via the gut-liver axis. The underlying mechanisms remain elusive. The aim of this study was to identify the specific pathways leading to gut barrier dysfunction in the ileum using a proteomics approach in a rat model. Male weanling Sprague Dawley rats were fed diets with adequate copper (CuA), marginal copper (CuM), or supplemented copper (CuS) in the absence or presence of fructose supplementation (CuAF, CuMF, and CuSF) for 4 weeks. Ileum protein was extracted and analyzed with an LC-MS. A total of 2847 differentially expressed proteins (DEPs) were identified and submitted to functional enrichment analysis. As a result, the ileum proteome and signaling pathways that were differentially altered were revealed. Of note, the CuAF is characterized by the enrichment of oxidative phosphorylation and ribosome as analyzed with the KEGG; the CuMF is characterized by an enriched arachidonic acid metabolism pathway; and focal adhesion, the regulation of the actin cytoskeleton, and tight junction were significantly enriched by the CuSF. In conclusion, our proteomics analysis identified the specific pathways in the ileum related to the different dietary doses of copper-fructose interactions, suggesting that distinct mechanisms in the gut are involved in the development of MASLD.

Chronic dietary exposure to a glyphosate-based herbicide alters ovarian functions in young female broilers

Glyphosate (GLY)-based herbicide (GBH) formulations are widely used pesticides in agriculture. The European Union recently decided to extend the use of GLY in Europe until 2034. Previously, we showed that chronic dietary GBH exposure in adult hens resulted in a reversible increase in early mortality in chicken embryos. In this present study, we investigated the GBH effects on metabolism and ovarian functions by using a transcriptomic approach in vivo in young female broilers and in vitro in ovarian explant cultures. We exposed 11-day-old female broilers to 13 mg GLY equivalent/kg body weight/day (GBH13, n = 20), 34 mg GLY equivalent/kg body weight/day (GBH34, n = 20), or a standard diet (control [CT], n = 20) for 25 days. These two GBH concentrations correspond to approximatively one eighth and one third of the no observed adverse effect level (NOAEL) as defined by European Food Safety Authority in birds. During this period, we evaluated body weight, fattening, food intake, and the weight of organs (including the ovaries). Chronic dietary GBH exposure dose dependently reduced food intake, body weight, and fattening, but increased oxidative stress and relative ovary weight. We analyzed the ovarian gene expression profile in CT, GBH13, and GBH34 broilers with RNA sequencing and showed that differentially expressed genes are mainly enriched in pathways related to cholesterol metabolism, steroidogenesis, and RNA processing. With quantitative polymerase chain reaction and western blotting, we confirmed that GBH decreased ovarian STAR and CYP19A1 messenger RNA and protein expression, respectively. Furthermore, we confirmed that GBH altered steroid production in ovarian explants. We have identified potential regulatory networks associated with GBH. These data provide valuable support for understanding the ovarian transcriptional regulatory mechanism of GBH in growing broilers.

Halogenated aromatic pollutants in routine animal-derived food of south China: Occurrence, sources, and dietary intake risks

Halogenated aromatic pollutants (HAPs) including polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated dibenzo-p-dioxins/furans (PBDD/Fs), and polybrominated diphenyl ethers (PBDEs) exhibit diverse toxicities and bio-accumulation in animals, thereby imposing risks on human via animal-derived food (ADF) consumption. Here we examined these HAPs in routine ADFs from South China and observed that PBDEs and PCBs showed statistically higher concentrations than PCDD/Fs and PBDD/Fs. PCDD/Fs and PCBs in these ADFs were mainly from the polluted feed and habitat of animals, except PCDD/Fs in egg, which additionally underwent selective biotransformation/progeny transfer after the maternal intake of PCDD/F-polluted stuff. PBDEs and PBDD/Fs were mostly derived from the extensive use of deca-BDE and their polluted environments. Significant interspecific differences were mainly observed for DL-PCBs and partly for PBDD/Fs and PBDEs, which might be caused by their distinct transferability/biodegradability in animals and the different living habit and habitat of animals. The dietary intake doses (DIDs) of these HAPs via ADF consumption were all highest for toddlers, then teenagers and adults. Milk, egg, and fish contributed most to the DIDs and risks for toddlers and teenagers, which results of several cities exceeded the recommended thresholds and illustrated noteworthy risks. Pork, fish, and egg were the top three risk contributors for adults, which carcinogenic and non-carcinogenic risks were both acceptable. Notably, PBDD/Fs showed the lowest concentrations but highest contributions to the total risks of these HAPs, thereby meriting continuous attention.

Amelioration of age-related cognitive decline and anxiety in mice by Centella asiatica extract varies by sex, dose and mode of administration.

Background: A water extract (CAW) of the Ayurvedic plant Centella asiatica administered in drinking water has been shown to improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice are compared. Methods: Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.2, 0.5 or 1% w/w) to provide 0, 200mg/kg/d, 500mg/kg/d or 1,000mg/kg/d CAW for a total of 5 weeks. An additional group of eighteen-month-old mice were treated with CAW (10mg/mL) in their drinking water CAW for a total of 5weeks to deliver the same exposure of CAW as the highest dietary dose (1,000mg/kg/d). CAW doses delivered were calculated based on food and water consumption measured in previous experiments. In the fourth and fifth weeks, mice underwent behavioral testing of cognition, anxiety and depression (n = 12 of each sex per treatment group in each test). Results: Aged mice of both sexes showed cognitive deficits relative to young mice while only female aged mice showed increased anxiety compared to the young female mice and no differences in depression were observed between the different ages. CAW (1,000mg/kg/d) in the drinking water improved deficits in aged mice in learning, executive function and recognition memory in both sexes and attenuated the increased measures of anxiety observed in the aged female mice. However, CAW in the diet only improved executive function in aged mice at the highest dose (1,000mg/kg/d) in both sexes and did so less robustly than when given in the water. There were no effects of CAW on depression-like behavior in aged animals regardless of whether it was administered in the diet or the water. Conclusions: These results suggest that CAW can ameliorate age-related changes in measures of anxiety and cognition and that the mode of administration is important for the effects of CAW on resilience to these age-related changes.

Optimum Doses and Forms of Selenium Maintaining Reproductive Health via Regulating Homeostasis of Gut Microbiota and Testicular Redox, Inflammation, Cell Proliferation, and Apoptosis in Roosters

BackgroundThere is a U-shaped relationship between dietary selenium (Se) ingestion and optimal sperm quality. ObjectivesThis study aimed to investigate the optimal dietary dose and forms of Se for sperm quality of breeder roosters and the relevant mechanisms. MethodsIn experiment 1, 18-wk-old Jingbai laying breeder roosters were fed a Se-deficient base diet (BD, 0.06 mg Se/kg), or the BD + 0.1, 0.2, 0.3, 0.4, 0.5, or 1.0 mg Se/kg for 9 wk. In experiment 2, the roosters were fed the BD or the BD + sodium selenite (SeNa), seleno-yeast (SeY), or Se-nanoparticles (SeNPs) at 0.2 mg Se/kg for 9 wk. ResultsIn experiment 1, added dietary 0.2 and 0.3 mg Se/kg led to higher sperm motility and lower sperm mortality than the other groups at weeks 5, 7, and/or 9. Furthermore, added dietary 0.2–0.4 mg Se/kg produced better testicular histology and/or lower testicular 8-hydroxy-deoxyguanosine than the other groups. Moreover, integrated testicular transcriptomic and cecal microbiomic analysis revealed that inflammation, cell proliferation, and apoptosis-related genes and bacteria were dysregulated by Se deficiency or excess. In experiment 2, compared with SeNa, SeNPs slightly increased sperm motility throughout the experiment, whereas SeNPs slightly reduced sperm mortality compared with SeY at week 9. Both SeY and SeNPs decreased malondialdehyde in the serum than those of SeNa, and SeNPs led to higher glutathione peroxidase (GPX) and thioredoxin reductase activities and GPX1 and B-cell lymphoma 2 protein concentrations in the testis compared with SeY and SeNa. ConclusionsThe optimal dietary Se dose for reproductive health of breeder roosters is 0.25–0.35 mg Se/kg, and SeNPs displayed better effects on reproductive health than SeNa and SeY in laying breeder roosters. The optimal doses and forms of Se maintain reproductive health of roosters associated with regulation intestinal microbiota homeostasis and/or testicular redox balance, inflammation, cell proliferation, and apoptosis.

Effects of l-ascorbic acid on growth, non-specific immunity, antioxidant capacity, and intestinal and hepatopancreatic histology of red swamp crayfish, Procambarus clarkii

This study investigated the dietary effects of coated l-ascorbic acid (LA) on growth, feed utilization, survival, serum biochemical indices, immunity, antioxidant capacity, and intestinal and hepatopancreatic histology of the pre-adult red swamp crayfish. Four isoproteinous and isolipidic diets were formulated to contain several LA levels as 0, 1300, 1600, and 1900 mg/kg and designated as control (LA0), LA13, LA16, and LA19, respectively. However, the analyzed LA concentrations in diets were 0.00, 199.57, 360.45, and 487.50 mg/kg in LA0, LA13, LA16, and LA19, respectively. Triplicate treatments of crayfish (21.60 ± 0.14 g) were fed the test diets and reared in fiberglass tanks with a density of 20 individuals per each for eight weeks. Results revealed that all LA treatments had significantly enhanced growth performance compared to the control. Of interest, the LA16 treatment recorded the highest final tank biomass, biomass gain, total feed intake, condition factor, and muscle yield among the other treatments. The tank feed conversion ratio was significantly decreased in LA treatments compared to the control. Moreover, dietary LA16 and LA19 had significantly higher survival rates (93.3%) compared to (85.0%) in the LA0 group. All dietary doses of LA significantly increased serum parameters (total protein, albumin, globulin, lysozyme activity) and respiratory burst activity compared to the LA0 treatment. Dietary LA16 significantly boosted the hepatopancreatic antioxidant capacity, manifested by decreased malondialdehyde concentrations, increased catalase, superoxide dismutase, and glutathione peroxidase enzyme activities, and reduced glutathione content compared to the LA-free diet. A normal histoarchitecture of the hepatopancreatic tubules was found in all LA treatments except with some minor degenerative changes in the tubular lumen, and hepatopancreatic cells associated with enlarged nuclei were found in the LA19. However, normal intestinal histoarchitecture was found in all treatments with no recorded intestinal lesions. Of interest, the polynomial regression performed on the analyzed LA concentrations suggested that 380 mg/kg would be suitable to provide maximal biomass gain for pre-adult crayfish. In conclusion, results revealed that coated LA could enhance the growth, immunity, and antioxidant capacity of pre-adult red swamp crayfish, suggesting its potential as a functional and necessary micronutrient for crayfish diets.

Biomarker responses and lethal dietary doses of tau-fluvalinate and coumaphos in honey bees: Implications for chronic acaricide toxicity

Evidence suggests that acaricide residues, such as tau-fluvalinate and coumaphos, are very prevalent in honey bee colonies worldwide. However, the endpoints and effects of chronic oral exposure to these compounds remain poorly understood. In this study, we calculated LC50 and LDD50 endpoints for coumaphos and tau-fluvalinate, and then evaluated in vivo and in vitro effects on honey bees using different biomarkers. The LDD50 values for coumaphos were 0.539, and for tau-fluvalinate, they were 12.742 in the spring trial and 8.844 in the autumn trial. Chronic exposure to tau-fluvalinate and coumaphos resulted in significant changes in key biomarkers, indicating potential neurotoxicity, xenobiotic biotransformation, and oxidative stress. The Integrated Biomarker Response was stronger for coumaphos than for tau-fluvalinate, supporting their relative lethality. This study highlights the chronic toxicity of these acaricides and presents the first LDD50 values for tau-fluvalinate and coumaphos in honey bees, providing insights into the risks faced by colonies.

Dietary Achievable Dose of Protocatechuic Acid, a Metabolite of Flavonoids, Inhibits High-Fat Diet-Induced Obesity in Mice.

Protocatechuic acid (PCA), a gut microbiota metabolite of flavonoids, inhibits dietary obesity and increases uncoupling protein 1 (UCP1), a critical regulator responsible for adipose thermogenesis; however, these effects are achieved at dietary unachievable (pharmacological) dose. It evaluates whether dietary achievable dose of PCA inhibits adiposity by activating adipose thermogenesis. Six-week-old male C57BL/6J mice are fed a high-fat diet (HFD) alone (control) or supplemented with 0.003% PCA w/w for 16 weeks. PCA consumption does not affect food intake but appreciably reduces body weight gain, improves insulin sensitivity, and attenuates hepatic steatosis. These effects are associated with no significant changes in the abundance of UCP1 in adipose tissues. Instead, PCA consumption increases the abundance and enzymatic activity of carnitine palmitoyltransferase 1 (the first rate-limiting enzyme in fatty acid oxidation) in the livers, inguinal white, and brown adipose tissues. Surprisingly, PCA at physiologically achievable dose does not affect the abundance and enzymatic activity of carnitine acyltransferase-1 expression and the capacity of fatty acid oxidation in 3T3-L1-derived white or brown adipocytes and human hepatoma HepG2 cells. Dietary achievable dose of PCA attenuates HFD-induced adiposity, which is likely achieved by increasing fatty acid oxidation other than activating adipose thermogenesis.

Utilization of Cottonseed Meal Protein Hydrolysate by Crustaceans: Insights on Growth Performance, Protein Turnover, and Metabolism in Chinese Mitten Crab Eriocheir sinensis

Plant protein hydrolysates could enhance the growth performance and diet utilization of aquaculture species. The mechanisms underlying their beneficial effects, however, remain unclear. The purpose of this study was to appraise the effects of cottonseed meal protein hydrolysate (CPH) supplementation on the growth performance, amino acid profiles, and protein turnover and metabolism of Eriocheir sinensis. A total of 240 crabs (initial weight: 37.32 ± 0.38 g) were randomly assigned to six groups, and fed six iso-protein feeds supplemented with varying levels of 0% (the control group), 0.2%, 0.4%, 0.8%, 1.6% and 3.2% of CPH. These diets were continuously fed to the crabs for 12 weeks. The findings demonstrated that, compared with the control group, adding 0.4–0.8% CPH to the diet significantly increased the specific growth rate, nitrogen retention efficiency, hepatopancreas index, body crude protein content, hepatopancreas alanine aminotransferase and glutamine synthetase activities, hemolymph total protein content, the hepatopancreas transcription of S6 kinase-poly-peptide 1, and the hepatopancreas protein levels of insulin-like growth factor-1 (IGF-1), protein kinase B (Akt), and target of rapamycin (TOR) of crabs. In contrast, when the dose of dietary CPH reached 3.2%, the forkhead box O1 (FoxO1) protein expression showed a significant decrease compared with the control group. In addition, CPH supplementation also increased the amount of amino acids and free amino acids in hepatopancreas and hemolymph, respectively. Together, these findings demonstrated that dietary supplementation of 0.4–0.8% CPH could activate the IGF-1/Akt/TOR pathway of E. sinensis, thereby improving growth performance, protein synthesis, and utilization. For cost considerations, the recommended dietary dose of CPH for E. sinensis is 0.8%. Due to the above benefits, CPH has the potential to be used as a growth promoter for other aquatic animals, especially crustaceans.

Comparative secretome metabolic dysregulation by six engineered dietary nanoparticles (EDNs) on the simulated gut microbiota

The potential use of engineered dietary nanoparticles (EDNs) in diet has been increasing and poses a risk of exposure. The effect of EDNs on gut bacterial metabolism remains largely unknown. In this study, liquid chromatography–mass spectrometry (LC-MS) based metabolomics was used to reveal significantly altered metabolites and metabolic pathways in the secretome of simulated gut microbiome exposed to six different types of EDNs (Chitosan, cellulose nanocrystals (CNC), cellulose nanofibrils (CNF) and polylactic-co-glycolic acid (PLGA); two inorganic EDNs including TiO2 and SiO2) at two dietary doses. We demonstrated that all six EDNs can alter the composition in the secretome with distinct patterns. Chitosan, followed by PLGA and SiO2, has shown the highest potency in inducing the secretome change with major pathways in tryptophan and indole metabolism, bile acid metabolism, tyrosine and phenol metabolism. Metabolomic alterations with clear dose response were observed in most EDNs. Overall, phenylalanine has been shown as the most sensitive metabolites, followed by bile acids such as chenodeoxycholic acid and cholic acid. Those metabolites might be served as the representative metabolites for the EDNs-gut bacteria interaction. Collectively, our studies have demonstrated the sensitivity and feasibility of using metabolomic signatures to understand and predict EDNs-gut microbiome interaction.

Potential Chemopreventive Effects of Dietary Combination of Phytochemicals against Cancer Development.

Cancer remains a major cause of cancer-related death worldwide. Over 70% of epithelial malignancies are sporadic and are related to lifestyle. Epidemiological studies suggest an inverse correlation between cancer incidence and fruit and vegetable intake. Numerous preclinical studies using in vitro (cell lines) and in vivo animal models of oncogenesis have reported the chemopreventive effects of dietary phytochemical agents through alterations in different biomarkers and signaling pathways. However, there is contrasting evidence from preclinical studies and clinical trials. To date, the most studied compounds include curcumin, resveratrol, isoflavones, green tea extract (epigallocatechin gallate), black raspberry powder (anthocyanins and ellagitannins), bilberry extract (anthocyanins), ginger extract (gingerol derivatives), and pomegranate extract (ellagitannins and ellagic acid). Overall, the clinical evidence of the preventive effects of dietary phytochemicals against cancer development is still weak, and the amount of these phytochemicals needed to exert chemopreventive effects largely exceeds the common dietary doses. Therefore, we propose a combination treatment of natural compounds that are used clinically for another purpose in order to obtain excess inhibitory efficacy via low-dose administration and discuss the possible reasons behind the gap between preclinical research and clinical trials.

PSV-13 Characterization of the Relative Abundance of Duodenal Mrna Related to Genes Involved in Copper Absorption in Different Breeds of Sheep

Abstract The objective of this experiment was to characterize relative expression of mRNA related to genes involved in Cu absorption in the duodenum of different breeds of sheep. Opportunistic liver and small intestine samples were collected from three harvested market weight Lincoln and Suffolk wether lambs (3 to 4 months of age) fed a low-quality forage based diet. A 5 cm sample of the duodenum (15 cm aboral from the pyloric sphincter) was collected from each lamb at the time of slaughter. Samples were immediately excised, sliced open, and washed with a PBS solution. The mucosal lining of the intestine was scraped with a scalpel blade to collect enterocytes. The scraped enterocytes were placed into a conical tube containing RNAlater. Furthermore, a one cm cubed sample from the center of the right lobe of the liver was collected from each lamb, washed with PBS solution, and stored in a conical tube until liver Cu concentrations could be determined. All intestinal and liver samples were stored at 4°C until transported back to the laboratory. Total enterocyte RNA was extracted and purified using TRI reagent and RNeasy. Primers for antioxidant 1 (ATOX1), Cu transporting alpha-polypeptide Atpase (ATP7A), Cu transporting beta-polypeptide Atpase (ATP7B), and Cu transporter1 (CTR1), were designed for real time PCR analysis. Liver Cu concentrations were decreased (P &amp;lt; 0.05) in Lincoln (225.3 ± 23.1 mg Cu/kg DM) compared with Suffolk lambs (342.1 ± 31.2 mg Cu/kg DM). The relative mRNA expression of ATOX1 (P &amp;lt; 0.05), ATP7B (P &amp;lt; 0.01), and CTR1 (P &amp;lt; 0.04) in duodenal enterocytes were decreased in Lincoln compared with Suffolk lambs. These data indicate that Cu absorption from the duodenum may be different in these breeds of sheep. Further research examining the impact of dietary Cu dose on genes involved in Cu absorption in different breeds of sheep as well as identification and quantification of proteins involved in Cu absorption, is warranted.