Short-term Intake Research Articles

The impact of a short-term high-fat diet on coagulation function in a mouse model and its role in exacerbating concanavalin A-induced liver injury

BackgroundRecently, the number of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced condition, metabolic dysfunction-associated steatohepatitis (MASH), has been increasing. These patients are at a higher risk of cardiovascular events and thromboembolism. However, the direct impact of high-fat diet (HFD), a cause of MASLD, on liver coagulation function is not well understood. Previously, we demonstrated that a short-term, 4-day intake of a HFD exacerbates concanavalin A (Con A)-induced acute liver injury in mice by promoting coagulation and inflammation. This model demonstrates that the liver exposed to a short-term HFD is vulnerable even before disease onset. In this study, using this model, we elucidated the detailed mechanisms by which short-term HFD intake promotes coagulation, considering primary and secondary hemostasis.MethodsC57BL/6 mice normally fed a normal diet (ND) were subjected to a HFD for 4 days. Liver tissue and blood samples were collected before and 4 and 24 h after Con A administration. Histological analysis, flow cytometry for platelet analysis, and blood coagulation tests related to secondary hemostasis were performed.ResultsEven with short-term consumption of a HFD alone, platelet and fibrinogen levels increased in the peripheral blood and liver. Additionally, when Con A was administered to mice on a short-term HFD, an increase in P-selectin expression was observed in the liver, with no upregulation in peripheral blood platelets. Furthermore, in mice subjected to a short-term HFD and treated with Con A, prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed.ConclusionsConsuming a HFD in short-term can enhance primary and secondary hemostasis, thereby increasing the risk of thrombosis. These conditions are presumed to be a risk factor that exacerbates Con A-induced liver injury. The findings provide insight into early intervention strategies for chronic liver diseases, such as MASLD and MASH.

Abstract 4121104: Fish Oil-Derived N-3 Very-Long-Chain Polyunsaturated Fatty Acids Improve Retinal Function in Aged Mice

Introduction: Epidemiological studies and clinical trials have revealed cardiometabolic benefits associated with dietary fish oil-derived omega-3 polyunsaturated fatty acids, particularly EPA and DHA. Omega-3 very-long-chain polyunsaturated fatty acids (VLCPUFA), synthesized in vivo by very-long-chain fatty acid elongase (ELOVL), e.g. ELOVL2 and 4, have recently garnered interest for their role in eye and cardiometabolic diseases. In our previous study, aging mice fed a VLCPUFA-rich diet for 8 weeks exhibited lowered plasma lipid levels, and repeated gavage of VLCPUFA in young mice resulted in improved retinal function. However, it is largely not known if VLCPUFA intake for a short term in aged mice would also improve retinal function and have beneficial effects in cardiometabolic risk factors. Hypothesis: We hypothesized that VLCPUFA may delay or rescue age-related vision loss by supplementing the products of ELOVL2, which decrease in quantity with age. We also hypothesize that short-term VLCPUFA intake may also confer favorable cardiometabolic benefits. Aims: We aimed to evaluate the effects of exogenous VLCPUFA on visual function and lipoprotein profiles in aged mice. Methods: Sixteen-month-old mice received a daily oral gavage of C24-28-rich VLCPUFA-oil (80 mg/kg BW) or an Intralipid vehicle for 15 consecutive days (n=8). The electroretinogram (ERG) instrument used was a UTAS E-3000 with gold corneal and stainless-steel scalp electrodes. Fast Protein Liquid Chromatography was performed using pooled plasma. Results: Consumption of VLCPUFA for 15 days increased scotopic a- (p < 0.05 at −5, 0, 5, 10, and 15 dB) and b-wave (p < 0.05 at 0 and 5 dB, p = 0.08 at 10 dB) amplitudes on ERG in both male and female mice compared with control. Although photopic ERG results did not exhibit statistically significant differences, likely due to low sample size, the overall results were consistent with those in our previous studies in young mice. We report no statistically significant difference in the composition of pro-atherogenic VLDL and LDL fractions due to VLCPUFA gavage. Increasing the duration and samples size in future gavage studies may be critical to determine the effects of VLCPUFA on eye and cardiovascular risk factors. Conclusions: This study revealed that a short-term oral administration of VLCPUFA was effective in improving ERG response overall, but not lipoprotein profiles.

Estimated human intake of endogenous and exogenous hormones from beef in the United States.

Endogenous and exogenous hormones may be present in beef. Human consumption of hormones has been linked to adverse health effects. To estimate daily intake of hormonal growth promotants (HGP) from beef consumed by the US population. We combined self-reported beef consumption information from a nationally-representative survey with concentrations of 12 HGP measured in 397 samples of retail beef/fat purchased in California. We defined typical, high, and maximum intake scenarios assuming self-reported consumed beef contained the mean, 95th percentile, and maximum concentrations of each HGP, respectively. We estimated distributions of usual (i.e., long-term) daily intake and short-term daily intake (µg/kg/day). We calculated the hazard quotient (HQ), or ratio of estimated intake to the World Health Organization's acceptable daily intake (ADI) for the HGP. The highest estimated HQs were found for melengestrol acetate (MGA). For usual daily intake under the typical intake scenario, no HQ exceeded 0.02 (0.00047 µg MGA/kg/day). Under the maximum intake scenario, the highest HQ was 0.29 (0.0087 µg MGA/kg/day), corresponding to the 99th percentile of intake among young boys (ages 1-5). The highest short-term intake estimates for MGA under the maximum intake scenario were the 99th percentile of intake among young girls and boys, which equaled (HQ = 1.00) or exceeded (HQ = 1.29) the ADI for MGA, respectively. Hormonal growth promotants (HGP) are used to increase beef production and have been linked to adverse reproductive effects. We estimated daily intake of MGA and several other HGP using US nationally-representative beef consumption data collected between 2015-2018 and HGP concentrations in retail beef. Estimated intake was highest for young children, but estimates were generally very low compared to current health-based intake limits. However, these limits are typically based on studies in adult animals, and further study of potential adverse effects during sensitive developmental periods, such as in early life, may be warranted to ensure recommended intake limits are health-protective.

Advanced Low-Cost Technology for Assessing Metal Accumulation in the Body of a Metropolitan Resident Based on a Neural Network Model.

This study is devoted to creating a neural network technology for assessing metal accumulation in the body of a metropolis resident with short-term and long-term intake from anthropogenic sources. Direct assessment of metal retention in the human body is virtually impossible due to the many internal mechanisms that ensure the kinetics of metals and the wide variety of organs, tissues, cellular structures, and secretions that ensure their functional redistribution, transport, and cumulation. We have developed an intelligent multi-neural network model capable of calculating the content of metals in the human body based on data on their environmental content. The model is two interconnected neural networks trained on actual measurement data. Since metals enter the body from the environment, the predictors of the model are metal content in drinking water and soil. In this case, water characterizes the short-term impact on the organism, and drinking water, combined with metal contents in soil, is a depository medium that accumulates metals from anthropogenic sources-the long-term impact. In addition, human physiological characteristics are taken into account in the calculations. Each period of exposure is taken into account by its neural network. Two variants of the model are proposed: open loop, where the calculation is performed by each neural network separately, and closed loop, where neural networks work together. The model built in this way was trained and tested on the data of real laboratory studies of 242 people living in different districts of Kazan. As a result, the accuracy of the neural network block for calculating long-term impact was 90% and higher, and the accuracy of the block for calculating short-term impact was 92% and higher. The closed double-loop model showed an accuracy of at least 96%. Conclusions: Our proposed method of assessing and quantifying metal accumulation in the body has high accuracy and reliability. It does not require expensive laboratory tests and allows quantifying the body's metal accumulation content based on readily available information. The calculation results can be used as a tool for clinical diagnostics and operational and planned management to reduce the levels of polymetallic contamination in urban areas.

Erythrocyte Selenium as a Potential Key Indicator for Selenium Supplementation in Low-Selenium Populations: A Selenium Supplementation Study Based on Wistar Rats.

Selenium (Se) is an essential trace element for maintaining human health, with significant antioxidant and immunoregulatory functions. Inadequate Se intake may be associated with Keshan disease, Kashin-Beck disease, and hypothyroidism. However, effective indicators for scientifically guiding Se supplementation in Se-deficient populations are still lacking. This study aims to explore the dynamic distribution of Se across various nutritional biomarkers and major organs in rats through a Se supplementation experiment, as well as the pairwise correlations between them, in order to identify reliable nutritional indicators for evaluating Se levels in the body. Se levels in hair, blood, and major tissues and organs were determined by atomic fluorescence spectrometry, and glutathione peroxidase (GSH-Px) levels were measured using an ELISA. Se supplementation significantly increased Se levels in rat blood, hair, and major organs, as well as GSH-Px levels in blood. Se primarily accumulated in the liver and kidneys, followed by myocardium, spleen, and muscles. Serum and plasma Se were found to be the best indicators of short-term Se intake, while erythrocyte Se levels showed a stronger correlation with Se levels in tissues and organs, making it a better marker for assessing long-term Se nutritional status compared to hair Se. This study demonstrates the potential of erythrocyte Se levels as an indicator for evaluating long-term Se nutritional status, providing scientific evidence for Se nutritional assessments.

Modification of the existing maximum residue levels for propamocarb in radishes (roots and small leaves).

In accordance with Article 6 of Regulation (EC) No 396/2005, the Federal Public Service (FPS) Health, Food chain Safety and Environment submitted a request to the competent national authority in Belgium (evaluating Member State, EMS) to modify the existing maximum residue levels (MRLs) for the active substance propamocarb in radishes for the residues occurring in radish roots and in small radish leaves (proposed to be classified under the subgroup of Roman rocket/rucola). The data submitted in support of the request were found to be sufficient to derive MRL proposals for radishes and small radish leaves. Adequate analytical methods for enforcement are available to control the residues of propamocarb on the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of propamocarb according to the reported agricultural practice is unlikely to present a risk to consumer health. The chronic consumer risk assessment shall be regarded as indicative since affected by uncertainty related to the data gaps identified in the MRL review.

Modification of the existing maximum residue level for flonicamid in honey.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant ISK Biosciences Europe N.V. submitted a request to the competent national authority in Finland to modify the existing maximum residue level (MRL) for the active substance flonicamid in honey. The data submitted in support of the request were not found appropriate to derive an MRL proposal for honey. The assessment was complemented by an analysis of the monitoring data available from the EU monitoring programmes (conducted during 2009-2023). The results from the monitoring data analysis suggest that the current MRL is still sufficient to account for the residue uptake in honey resulting from plant protection products uses of flonicamid on melliferious crops. Adequate analytical methods for enforcement are available to control the residues of flonicamid in honey according to the residue definition as the sum of flonicamid, TFNA and TFNG, expressed as flonicamid at the validated limit of quantification (LOQ) of 0.01 mg/kg for each compound. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues in honey at a level of 0.05 mg/kg according to the monitoring data is unlikely to present a risk to consumer health.

Modification of the existing maximum residue levels for dichlorprop-P in cereal grains.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Nufarm Crop Products UK Ltd. submitted a request to the competent national authority in Italy to modify the existing maximum residue levels (MRLs) for the active substance dichlorprop-P in barley, oat, rye and wheat grain. The data submitted in support of the request were found to be sufficient to derive MRL proposals for these cereal grains. Adequate analytical methods for enforcement are available to control the residues of dichlorprop-P in the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg and in animal matrices at the validated LOQ of 0.01 mg/kg. Based on the risk assessment results, the European Food Safety Authority (EFSA) concluded that the short-term and long-term intake of residues resulting from the use of dichlorprop-P-2-ethylhexyl (dichlorprop-P 2-EHE) according to the reported agricultural practices is unlikely to present a risk to consumer health.

Identification and Replication of Urine Metabolites Associated With Short-Term and Habitual Intake of Sweet and Fatty Snacks in European Children and Adolescents

BackgroundIntake of sweet and fatty snacks may partly contribute to the occurrence of obesity and other health conditions in childhood. Traditional dietary assessment methods may be limited in accurately assessing the intake of sweet and fatty snacks in children. Metabolite biomarkers may aid the objective assessment of children’s food intake and support establishing diet–disease relationships. ObjectivesThe present study aimed to identify biomarkers of sweet and fatty snack intake in 2 independent cohorts of European children. MethodsWe used data from the IDEFICS/I.Family cohort from baseline (2007/2008) and 2 follow-up examination waves (2009/2010 and 2013/2014). In total, 1788 urine samples from 599 children were analyzed for untargeted metabolomics using high-resolution liquid chromatography-mass spectrometry. Short-term dietary intake was assessed by 24-h dietary recalls, and habitual dietary intake was calculated with the National Cancer Institute method. Data from the Dortmund Nutritional and Anthropometric Longitudinal Designed (DONALD) cohort of 24-h urine samples (n = 567) and 3-d weighted dietary records were used for external replication of results. Multivariate modeling with unbiased variable selection in R algorithms and linear mixed models were used to identify novel biomarkers. Metabolite features significantly associated with dietary intake were then annotated. ResultsIn total, 66 metabolites were discovered and found to be statistically significant for chocolate candy; cakes, puddings, and cookies; candy and sweets; ice cream; and crisps. Most of the features (n = 62) could not be annotated. Short-term and habitual chocolate intake were positively associated with theobromine, xanthosine, and cyclo(L-prolyl-L-valyl). These results were replicated in the DONALD cohort. Short-term candy and sweet intake was negatively associated with octenoylcarnitine. ConclusionsOf the potential metabolite biomarkers of sweet and fatty snacks in children, 3 biomarkers of chocolate intake, namely theobromine, xanthosine, and cyclo(L-prolyl-L-valyl), are externally replicated. However, these potential biomarkers require further validation in children.

Modification of the existing maximum residue levels for cycloxydim in various crops.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF SE submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRLs) for the active substance cycloxydim in pome fruits, apricots/peaches, peas (with pods), maize/corn, sugar beet roots and milk (sheep). The data submitted in support of the request were found to be sufficient to derive MRL proposals for pome fruits, peas (with pods), maize/corn and sugar beet roots while for apricots, peaches and sheep milk no changes to the existing MRLs were considered necessary. Adequate analytical methods for enforcement are available to control the residues of cycloxydim according to the current enforcement residue definition in the commodities under consideration. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the uses of cycloxydim according to the reported agricultural practices is unlikely to present a risk to consumer health.

Assessment of the hormesis effect and toxic damage of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus)

The present study was conducted to evaluate the hormesis and toxicity of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus). Triplicate isonitrogenous and isocaloric aflatoxin B1 diets—CD (control, 0 ug/kg), D1 (20 ug/kg), and D2 (500 ug/kg)—were prepared and fed to grass carp with an initial mean body weight of (15.2 ± 0.1) g for 56 days. The results showed that the weight gain rate and specific growth rate of grass carp fed diet D2 were significantly higher, and the feed coefficient and crude fat content of the whole body were significantly lower (P < 0.05) compared with those fed diet CD. Serum superoxide dismutase content of grass carp fed D1 diet increased significantly (P < 0.05) with an increasing dose of aflatoxin B1, but when the dose reached 500 ug/kg (D2), serum superoxide dismutase, complement C3, and immunoglobulin M of grass carp decreased significantly (P < 0.05), while malondialdehyde increased significantly (P < 0.05). After short-term feeding of aflatoxin B1-containing diets (D1 and D2), liver body index, visceral body index, serum total cholesterol, triglyceride, and urea nitrogen content of grass carp increased significantly (P < 0.05), total bile acid secretion decreased significantly (P < 0.05), and structural damages such as increase in vacuoles, organizational structure loosening, and nucleus translocation were observed in the liver. Meanwhile, liver function indexes such as serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased significantly with the increase of aflatoxin B1 dose (P < 0.05). In addition, the height of intestinal villi, crypt depth, villus–crypt ratio, and tubular cell number, as well as the content of trypsin and lipase activities in the intestine of grass carp in the D2 group, were significantly higher than those in the CD group (P < 0.05). In conclusion, after a short-term intake of low doses of aflatoxin B1 (≤500 ug/kg), the toxicological damage of aflatoxin B1 was pronounced, although it produced a certain degree of hormesis on the growth performance and intestinal structure and function of grass carp. At a dose of 20 ug/kg, the non-specific immune system and liver structure and function of grass carp showed obvious toxic damage.

Spinal cord microglia drive sex differences in ethanol-mediated PGE2-induced allodynia

The mechanisms of how long-term alcohol use can lead to persistent pain pathology are unclear. Understanding how earlier events of short-term alcohol use can lower the threshold of non-painful stimuli, described as allodynia could prove prudent to understand important initiating mechanisms. Previously, we observed that short-term low-dose alcohol intake induced female-specific allodynia and increased microglial activation in the spinal cord dorsal horn. Other literature describes how chronic ethanol exposure activates Toll-like receptor 4 (TLR4) to initiate inflammatory responses. TLR4 is expressed on many cell types, and we aimed to investigate whether TLR4 on microglia is sufficient to potentiate allodynia during a short-term/low-dose alcohol paradigm. Our study used a novel genetic model where TLR4 expression is removed from the entire body by introducing a floxed transcriptional blocker (TLR4-null background (TLR4LoxTB)), then restricted to microglia by breeding TLR4LoxTB animals with Cx3CR1:CreERT2 animals. As previously reported, after 14 days of ethanol administration alone, we observed no increased pain behavior. However, we observed significant priming effects 3 hrs post intraplantar injection of a subthreshold dose of prostaglandin E2 (PGE2) in wild-type and microglia-TLR4 restricted female mice. We also observed a significant female-specific shift to pro-inflammatory phenotype and morphological changes in microglia of the lumbar dorsal horn. Investigations in pain priming-associated neuronal subtypes showed an increase of c-Fos and FosB activity in PKCγ interneurons in the dorsal horn of female mice directly corresponding to increased microglial activity. This study uncovers cell- and female-specific roles of TLR4 in sexual dimorphisms in pain induction among non-pathological drinkers.

A Mouse Model for Conditional Expression of Activated β-Catenin in Epidermal Keratinocytes

We report the generation and characterization of the K5: CAT bigenic mouse in which the constitutively activated form of β-catenin (ΔN89 β-catenin) is conditionally expressed in cytokeratin-5 (K5) positive epidermal keratinocytes. Following short-term doxycycline intake during the telogen resting phase, the adult K5: CAT bigenic develops enlarged pilosebaceous units that expand deep into the dermis, an expansion usually observed during the anagen growth phase. Prolonged doxycycline treatment results in significant thickening and folding of the K5: CAT epidermis. During this persistent induction period, there is clear evidence of increased keratinocyte proliferation, particularly in the epidermal basal cell layer and the outer root sheath of the hair follicle. This unscheduled increase in cellular proliferation likely explains the decrease in hair density observed in the K5: CAT mouse following persistent doxycycline intake. Numerous hyperplastic endometrioid cysts, which display cornification toward their lumens, are also observed during this treatment period. Remarkably, de-induction of ΔN89 β-catenin expression through doxycycline withdrawal results in a marked reversal of the skin phenotype, suggesting that these morphological changes are dependent on continued signaling by β-catenin and/or its downstream molecular mediators. Joining a small group of mouse models for conditional β-catenin signaling, our K5: CAT mouse model will be particularly useful in identifying those molecular mediators of β-catenin that are responsible for initiating and maintaining these phenotypic responses in the K5: CAT skin. Such studies are predicted to shed more light on β-catenin signaling in epidermal epithelial morphogenesis, hair follicle cycling, and hair growth pathologies.

Modification of the existing maximum residue level for methoxyfenozide in aubergines.

In accordance with Article 6 of Regulation (EC) No 396/2005, the Federal Public Service (FPS) Health, Food chain Safety and Environment submitted a request on behalf of Belgium (evaluating Member State, EMS) to modify the existing maximum residue level (MRL) for the active substance methoxyfenozide in aubergines/eggplants. The data submitted in support of the request were found to be sufficient to derive an MRL proposal for aubergines/eggplants. Adequate analytical methods for enforcement are available to control the residues of methoxyfenozide in the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, the EFSA concluded that the short-term and long-term intake of residues resulting from the indoor use of methoxyfenozide according to the reported agricultural practice is unlikely to present a risk to consumer health.

Fried Soybean Oil Causes Systemic Low-Grade Inflammation by Disrupting the Balance of Gut Microbiota in Mice.

Previous reports have mainly investigated the long-term effects (>30 d), such as gut microbiota dysbiosis and systemic low-grade inflammation, in mice fed fried oil. However, short-term intake of deep-fried oil is more likely to occur in daily life, and such studies are lacking. This study aimed to investigate the short-term effects of fried oil intake on systemic low-grade inflammation. Male Kunming mice were fed non-fried soybean oil or low (25%), medium (50%), or high (100%)-fried oil at 4.4 g/kg for 6 d. Serum and fecal samples were collected on day 7. In all groups fed fried oil, the serum levels of tumor necrosis factor (TNF-α) were significantly elevated 2-4-fold. Among the gut microbiota, the abundance of Alloprevotella significantly decreased by up to 76%, while Lactobacilli significantly increased by up to 385%. The fecal valeric acid content was significantly increased and positively correlated with TNF-α levels. Both valeric acid and TNF-α levels were positively correlated with the abundance of Lactobacilli and negatively correlated with that of Alloprevotella. In summary, a short-term ingestion of even low doses of fried oil alters the gut microbiota Alloprevotella and Lactobacilli and increases fecal valeric acid content, which correlates with increased serum TNF-α levels.

Effects of short-term pre-competition weight loss on certain physiological parameters and strength change in elite boxers.

Athletes in certain sports aim to gain an advantage by competing in a lower body mass class instead of competing in their own body mass class. This study aims to reveal certain physiologic and strength changes in elite male boxers who lost body mass rapidly before the competition. 30 thirty boxers who were aged between 19-24 years and having a mean age of 7.4 years participated in the study. To evaluate the effect of short-term dietary intake interventions on body composition and muscle strength before the competition, boxers were divided into three groups: control (C), exercise+diet1 (E+D1) and exercise+diet2 (E+D2) groups. The dietary habits of the participants were controlled and they participated in the training program. The data of the study consisted of variables such as body mass, height, regional muscle mass, body fat percentage, biceps and femur bicondylar circumference measurements before the competitions. Isometric strength measurements of knee extensors and flexors and shoulder internal and external rotators were also recorded. Physiologic parameters such as body mass change, BMI level, body fat percentage and leg muscle ratios of E+D2 were significantly decreased compared to C and E+D1 groups. Furthermore, submaximal and maximal strength production in knee extensors and flexors as well as shoulder internal and external rotators were significantly decreased in E+D2 compared to C and E+D1 groups. The tendency to lose body mass quickly in a short of time may give the desired results in terms of BMI, body mass and fat percentage, but it may cause strength losses in boxers during the competition period.

Metabolic Effects of Short-Term High-Fat Intake Vary Depending on Dietary Amino Acid Composition

BackgroundIt is generally accepted that excessive fat intake has undesirable effects on the energy metabolism of our body. Dietary amino acid composition is also critical to the regulation of lipid metabolism. ObjectivesThis study aimed to investigate whether high-fat diets (HFDs) with different amino acid deficiencies lead to different metabolic outcomes. MethodsSix-wk-old male Wistar rats were fed either a control diet (CN; 3.7 kcal/g, 12% calories from fat) or HFDs (5.1 kcal/g, 60% calories from fat) with 7 different amino acid compositions [control or methionine, arginine, histidine, lysine, threonine, or branched-chain amino acids (BCAAs) deficient], for 7 d. Tissue weights and lipid accumulation in the liver, skeletal muscle, and adipose tissue were measured, and serum biochemical parameters were analyzed. ResultsAlthough the food intake of the HFD groups was a little less than that of the CN group, the total calorie intakes were comparable among the groups, except for histidine-deficient and BCAA-deficient groups. In rats fed am HFD with a control amino acid composition (HFCN), dramatic increase in triglyceride (TG) accumulation in the liver and serum LDL cholesterol concentration were observed compared with the CN group. However, when the arginine content in the diet was reduced, liver TG accumulation was completely inhibited, with no apparent effects on serum lipoprotein-cholesterol concentrations. Meanwhile, deficiency of the other amino acids, such as threonine, reversed HFD-induced upregulation of serum LDL cholesterol. ConclusionsIt is observed that although the rats ingested an excessive amount of fat, neither ectopic fat accumulation nor dyslipidemia were always induced at least in the short term; hence, the consequent metabolic change was dependent on the dietary amino acid composition. These findings introduce an important perspective regarding HFD regimens in both scientific and clinical contexts.

Balancing sodium and potassium: Implication of mTORC2-mediated ENaC activation in DCT2 and early CNT for potassium balance in high dietary potassium

Background: The activity of the epithelial sodium ion channel, ENaC, and ENaC-dependent potassium (K+) secretion through ROMK are influenced by both aldosterone-dependent and independent mechanisms in response to dietary potassium (K+). While ENaC activity in the late connecting tubule (CNT) and cortical collecting duct (CCD) depends on aldosterone, it is aldosterone-independent in the late distal convoluted tubule (DCT2) and early CNT (eCNT). Aldosterone-stimulated ENaC activity relies on SGK1, transcriptionally upregulated by aldosterone and subsequently phosphorylated and activated by mTOR complex-2 (mTORC2). Recent evidence suggests that high potassium can rapidly activate mTORC2/SGK1 signaling to stimulate ENaC. In this study, we explore mTORC2’s role in K+ secretion and aldosterone-independent ENaC regulation. Methods: Rictor, a core component of mTORC2, was selectively knocked out (KO'd) in DCT2, CNT and CD by utilizing Calbindin as Cre-driver (CRKO mice) or late CNT and CD, by employing AQP2 as the Cre-driver (ARKO mice). Both wild-type (WT) and KO mice were subjected to a high potassium (HK) diet for short-term (4 hours) or medium-term (48 hours) periods, enabling the monitoring of both the early response and prolonged adaptation to the HK diet. Parameters assessed include urinary and blood electrolyte levels, renal transporter expression, activity and localization, and mTORC2 target phosphorylation. Results: On a normal K+ diet, both KO mice maintained Na+ and K+ balance but CRKO mice had elevated aldosterone levels. After short-term (4-hour) HK intake, CRKO mice had disrupted Na+ and K+ balance, reduced K+ excretion and hyperkalemia. In contrast, ARKO mice maintained Na+ and K+ balance with elevated aldosterone. On a prolonged HK diet (48 hours), CRKO mice had severe hyperkalemia, reduced GFR and significantly elevated aldosterone level. Immunofluorescence studies indicated markedly reduced apical localization of active ENaC in DCT2/eCNT of CRKO mice. Conversely, ENaC apical localization in the late CNT and CCD was mostly unaffected. Phosphorylation of mTORC2 targets involved in ENaC regulation, such as SGK1, and SGK1’s target, Nedd4-2, was also reduced in CRKO mice. ARKO mice maintained ion balance with normal K+ levels but significantly increased aldosterone levels and maintained ENaC apical localization in the late CNT and CCD. Conclusions: The data suggest that high aldosterone can compensate mTORC2 deficiency and maintain ENaC activity in the late CNT and CCD. However, mTORC2 activity is crucial for maintaining ENaC activity in the late DCT and early CNT (aldosterone-independent) and preserving potassium balance during high dietary potassium intake. National Institutes of Health (R01- DK56695), James Hilton Manning and Emma Austin Manning Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Higher Expression of miR-15b-5p with Inclusion of Fresh, Lean Beef as Part of a Healthy Dietary Pattern Is Inversely Associated with Markers of Cardiometabolic Disease Risk

BackgroundConsiderable controversy exists surrounding the consumption of red meat and its impacts on cardiometabolic health and if it may further impact risk factors at the molecular level. ObjectiveThe purpose of this study was to examine the acute effects of dietary patterns, varying in red meat quantity, on the expression of circulating microRNAs (miRNAs), which are emerging biomarkers of metabolic dysfunction and chronic disease severity. MethodsSecondary analyses were performed on plasma samples collected within a randomized, crossover design study in 16 women with overweight (mean ± standard deviation, age = 33 ± 9.89 y; body mass index = 27.9 ± 1.66 kg/m2). Participants were provided with eucaloric, isonitrogenous diets (15% of daily intake as protein) containing either 2 servings of fresh, lean beef/day (BEEF) or 0 servings of fresh, lean beef/day (PLANT) for 7 d/pattern. Fasting blood samples were collected at the end of each dietary pattern for the assessment of 12 circulating metabolic miRNA expression levels (determined a priori by quantitative reverse transcriptase-polymerase chain reaction), plasma glucose, insulin, interleukin-6, tumor necrosis factor-α, C-reactive protein (CRP), adiponectin, glucagon-like peptide-1, and branched-chain amino acids. ResultsOf the 12 miRNAs, miR-15b-5p expression was higher following BEEF versus PLANT (P = 0.024). Increased miR-15b-5p expression correlated with decreased fasting CRP (r = −0.494; P = 0.086) and insulin concentrations (r = −0.670; P = 0.017). miR-15b-5p was inversely correlated with insulin resistance (r = −0.642; P = 0.024) and β cell function (r = −0.646; P = 0.023) and positively correlated with markers of insulin sensitivity (r = 0.520; P = 0.083). However, the correlations were only observed following BEEF, not PLANT. ConclusionsThese data indicate that the short-term intake of fresh, lean beef as part of a healthy dietary pattern impacts potential biomarkers of cardiometabolic health that are associated with cardiometabolic risk factors in women with overweight.This study was registered at clinicaltrials.gov as NCT02614729.

Modification of the existing maximum residue levels for fluxapyroxad in kaki/Japanese persimmons and cultivated mushrooms.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF SE submitted two requests to the competent national authority in Spain and Ireland to modify the existing maximum residue levels (MRLs) for the active substance fluxapyroxad in kaki/Japanese persimmons and in cultivated fungi, respectively. The data submitted in support of the requests were found to be sufficient to derive MRL proposals for kaki/Japanese persimmons and cultivated fungi. Adequate analytical methods for enforcement are available to control the residues of fluxapyroxad on the commodities under consideration at the validated LOQ of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of fluxapyroxad, according to the reported agricultural practices, is unlikely to present a risk to consumer health. The long-term consumer risk assessment is indicative, pending the submission of the confirmatory data requested under the MRL review.