Weeks Of Diet Research Articles

Maternal pea fiber supplementation to a high calorie diet in obese pregnancies protects male offspring from metabolic dysfunction in adulthood.

We investigated the influence of maternal yellow-pea fiber supplementation in obese pregnancies on offspring metabolic health in adulthood. Sixty newly-weaned female Sprague-Dawley rats were randomized to either a low-calorie control diet (CON) or high calorie obesogenic diet (HC) for 6-weeks. Obese animals were then fed either the HC diet alone or the HC diet supplemented with yellow-pea fiber (HC + FBR) for an additional 4-weeks prior to breeding and throughout gestation and lactation. On postnatal day (PND) 21, 1 male and 1 female offspring from each dam were weaned onto the CON diet until adulthood (PND 120) for metabolic phenotyping. Adult male, but not female, HC offspring demonstrated increased body weight and feed intake vs CON offspring, however no protection was offered by maternal FBR supplementation. HC male and female adult offspring demonstrated increased serum glucose and insulin resistance (HOMA-IR) compared with CON offspring. Maternal FBR supplementation improved glycemic control in male, but not female offspring. Compared with CON offspring, male offspring from HC dams demonstrated marked dyslipidemia (higher serum cholesterol, increased number of TG-rich lipoproteins, and smaller LDL particles) which was largely normalized in offspring from HC + FBR mothers. Male offspring born to obese mothers (HC) had higher hepatic TG, which tended to be lowered (p = 0.07) by maternal FBR supplementation.Supplementation of a maternal high calorie diet with yellow-pea fiber in prepregnancy and throughout gestation and lactation protects male offspring from metabolic dysfunction in the absence of any change in body weight status in adulthood.

Hepatocyte-targeted siTAZ therapy lowers liver fibrosis in NASH diet-fed chimeric mice with hepatocyte-humanized livers

Nonalcoholic steatohepatitis (NASH) is emerging as the most common cause of liver disease. Although many studies in mouse NASH models have suggested therapies, translation to humans is poor, with no approved drugs for NASH. One explanation may lie in differences between mouse and human hepatocytes. We used NASH diet-fed chimeric mice reconstituted with human hepatocytes (hu-liver mice) to test a mechanism-based hepatocyte-targeted small interfering RNA (siRNA), GalNAc-siTaz, shown previously to block the progression to fibrotic NASH in mice. Following ablation of endogenous hepatocytes, male mice were reconstituted with human hepatocytes from a single donor with the rs738409-C/G PNPLA3 risk variant, resulting in ∼95% human hepatocyte reconstitution. The mice were then fed a high-fat choline-deficient l-amino acid-defined diet for 6weeks to induce NASH, followed by six weekly injections of GalNAc-siTAZ to silence hepatocyte-TAZ or control GalNAc-siRNA (GalNAc-control) while still on the NASH diet. GalNAc-siTAZ lowered human hepatic TAZ and IHH, a TAZ target that promotes NASH fibrosis. Most important, GalNAc-siTAZ decreased liver inflammation, hepatocellular injury, hepatic fibrosis, and profibrogenic mediator expression versus GalNAc-control, indicating that GalNAc-siTAZ decreased the progression of NASH in mice reconstituted with human hepatocytes. In conclusion, silencing TAZ in human hepatocytes suppresses liver fibrosis in a hu-liver model of NASH.

Signs of Glucagon Resistance After a 2-Week Hypercaloric Diet Intervention.

Hyperglucagonemia is observed in individuals with obesity and contributes to the hyperglycemia of patients with type 2 diabetes. Hyperglucagonemia may develop due to steatosis-induced hepatic glucagon resistance resulting in impaired hepatic amino acid turnover and ensuing elevations of circulating glucagonotropic amino acids. We evaluated whether glucagon resistance could be induced in healthy individuals by a hypercaloric diet intervention designed to increase hepatic fat content. We recruited 20 healthy male individuals to follow a hypercaloric diet and a sedentary lifestyle for 2 weeks. Amino acid concentrations in response to infusion of glucagon were assessed during a pancreatic clamp with somatostatin and basal insulin. The reversibility of any metabolic changes was assessed 8 weeks after the intervention. Hepatic steatosis was assessed by magnetic resonance spectroscopy. The intervention led to increased hepatic fat content (382% [206%; 705%], P < .01). Glucagon infusion led to a decrease in the concentration of total amino acids on all experimental days, but the percentage change in total amino acids was reduced (-2.5% ± 0.5% vs -0.2% ± 0.7%, P = .015) and the average slope of the decline in the total amino acid concentration was less steep (-2.0 ± 1.2 vs -1.2 ± 0.3 μM/min, P = .016) after the intervention compared to baseline. The changes were normalized at follow-up. Our results indicate that short-term unhealthy behavior, which increases hepatic fat content, causes a reversible resistance to the effect of glucagon on amino acid concentrations in healthy individuals, which may explain the hyperglucagonemia associated with obesity and diabetes.

Ameliorative effects of Dunaliella salina microalgae on nanoparticle (ZnO NPs)-induced toxicity in fish.

Dunaliella salina (D. salina) is a well-known microalga that contains considerable amounts of nutritious and medicinal bioactive components. This work studied the modulatory role of D. salina against zinc oxide nanoparticle (ZnO NPs)-induced neurotoxic effects in adult zebrafish. Fishes were subjected to 0.69mg L-1 (1/5th 96-h LC50) for 4weeks; then, fishes were supplemented with D. salina in the diet for 2weeks at two levels (15 and 30%). Exposure to ZnO NPs induced a significant increase in the levels of reactive oxygen species (ROS), hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) while accompanied with downregulation of antioxidant genes in the brain of exposed fishes. Brain neurochemistry and enzyme activities were also altered following ZnO NP exposure. ZnO NPs significantly reduced the neurotransmitters and acetylcholinesterase (AchE) activity while increasing Alzheimer's disease-related proteins and inflammatory response via upregulation of tumor necrosis factor (TNF-α). Additionally, ZnO NPs increased the indices of brain's DNA oxidative damage, increasing brain tissue's metallothionein (MT) and zinc residues. ZnO NPs upregulated the transcription patterns of apoptosis-related genes (casp3 and p53). D. salina dietary co-supplementation with ZnO NPs alleviated the ZnO NPsZnO NP-induced neuro-oxidative damages by lowering the lipid, DNA damage, and inflammatory biomarkers. Besides, D. salina alleviating responses were linked with increasing the levels of the assessed antioxidants. Conclusively, D. salina dietary supplementation induced potential alleviating effects of the ZnO NP-induced neurotoxicity in adult zebrafish.

PCSK7: A novel regulator of apolipoprotein B and a potential target against non-alcoholic fatty liver disease

BackgroundEpidemiological evidence links the proprotein convertase subtilisin/kexin 7 (PCSK7) to triglyceride (TG) metabolism. We associated the known PCSK7 gain-of-function non-coding SNP rs236918 with higher levels of plasma apolipoprotein B (apoB) and the loss-of-function coding variant p.Pro777Leu (SNP rs201598301) with lower apoB and TG. Herein, we aimed to unravel the in vivo role of liver PCSK7. MethodsWe biochemically defined the functional role of PCSK7 in lipid metabolism using hepatic cell lines and Pcsk7−/− mice. Our findings were validated following subcutaneous administration of hepatocyte-targeted N-acetylgalactosamine (GalNAc)-antisense oligonucleotides (ASOs) against Pcsk7. ResultsIndependent of its proteolytic activity, membrane-bound PCSK7 binds apoB100 in the endoplasmic reticulum and enhances its secretion. Mechanistically, the loss of PCSK7/Pcsk7 leads to apoB100 degradation, triggering an unfolded protein response, autophagy, and β-oxidation, eventually reducing lipid accumulation in hepatocytes. Non-alcoholic fatty liver disease (NAFLD) was induced by a 12-week high fat/fructose/cholesterol diet in wild type (WT) and Pcsk7−/− mice that were then allowed to recover on a 4-week control diet. Pcsk7−/− mice recovered more effectively than WT mice from all NAFLD-related liver phenotypes. Finally, subcutaneous administration of GalNAc-ASOs targeting hepatic Pcsk7 to WT mice validated the above results. ConclusionsOur data reveal hepatic PCSK7 as one of the major regulators of apoB, and its absence reduces apoB secretion from hepatocytes favoring its ubiquitination and degradation by the proteasome. This results in a cascade of events, eventually reducing hepatic lipid accumulation, thus supporting the notion of silencing PCSK7 mRNA in hepatocytes for targeting NAFLD.

The alleviating effect of Scutellaria amoena extract on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NLRP3/ASC/caspase-1 axis.

Background: Scutellaria amoena (SA) is the root of S. amoena C.H. Wright of Labiatae, also known as Scutellaria southwestern. This is mainly distributed in Sichuan, Yunnan, and Guizhou in China. In southwest China, SA is used as an alternative method to genuine medicine for the treatment of allergy, diarrhea, inflammation, hepatitis, and bronchitis. Thus far, studies on the effects of SA on non-alcoholic steatohepatitis (NASH) are lacking. This paper investigated the effect of SA on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NOD-like receptor 3 (NLRP3)/apoptosis-associated speck-like protein (ASC)/caspase-1 axis. Methods: A NASH rat model was induced by a high-fat diet (HFD) for 12weeks, and rats were orally given different doses of SA extracts (150 and 300mg/kg/d) for 6weeks. Changes in histological parameters, body weight, organ indexes, cytokines, and biochemical parameters related to NLRP3 in NASH rats were checked. 16S rRNA gene sequencing and UPLC-MS/MS technology were used to analyze the changes in the gut microbiota composition and its metabolites in NASH rats. Results: SA significantly inhibited the HFD-induced increase in body weight, lipid levels, and inflammatory infiltration. SA notably inhibited the HFD-induced increase in the upper and lower factors of NLRP3, such as transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, pro-IL-18, IL-1β, pro-IL-1β, NLRP3, ASC, and caspase-1. Additionally, mRNA expressions of caspase-1, NLRP3, and ASC were significantly downregulated after SA treatment. The results of the intestinal flora showed that SA could increase the diversity of flora and change its structure and composition in NASH rats by reducing Firmicutes/Bacteroidetes (F/B) ratio, Blautia (genus), Lachospiraceae (family), and Christensenellaceae R-7 group (genus), and increasing Muribaculaceae (family) and Bacteroides (genus). The metabolomics revealed that 24 metabolites were possibly the key metabolites for SA to regulate the metabolic balance of NASH rats, including chenodeoxycholic acid, xanthine, and 9-OxoODE. Nine metabolic pathways were identified, including primary bile acid biosynthesis, bile secretion, purine metabolism, and secondary bile acid biosynthesis. Conclusion: SA can regulate the intestinal microbial balance and metabolic disorder by inhibiting the NLRP3/ASC/caspase-1 axis to relieve NASH.

A low-fat diet improves fatigue in multiple sclerosis: Results from a randomized controlled trial

Background: Fatigue can be a disabling multiple sclerosis (MS) symptom with no effective treatment options. Objective: Determine whether a low-fat diet improves fatigue in people with MS (PwMS). Methods: We conducted a 16-week randomized controlled trial (RCT) and allocated PwMS to a low-fat diet (active, total daily fat calories not exceeding 20%) or wait-list (control) group. Subjects underwent 2 weeks of baseline diet data collection (24-hour diet recalls (24HDRs)), followed by randomization. The active group received 2 weeks of nutrition counseling and underwent a 12-week low-fat diet intervention. One set of three 24HDRs at baseline and week 16 were collected. We administered a food frequency questionnaire (FFQ) and Modified Fatigue Impact Scale (MFIS) every 4 weeks. The control group continued their pre-study diet and received diet training during the study completion. Results: We recruited 39 PwMS (20—active; 19—control). The active group decreased their daily caloric intake by 11% (95% confidence interval (CI): −18.5%, −3.0%) and the mean MFIS by 4.0 (95% CI: −12.0, 4.0) compared to the control (intent-to-treat). Sensitivity analysis strengthened the association with a mean MFIS difference of −13.9 (95% CI: −20.7, −7.2). Conclusions: We demonstrated a significant reduction in fatigue with a low-fat dietary intervention in PwMS.

SAT679 Telehealth And Metabolic Health: Unraveling The Effects Of A 12-week Low-starch Diet On Homa2B IR In Overweight Women

Abstract Disclosure: G. Erta: None. G. Gersone: None. P. Tretjakovs: None. Background: Telehealth has emerged as a promising approach for delivering health care interventions remotely, allowing increased access and convenience, especially in the context of lifestyle interventions for metabolic health. In this study, our aim was to investigate the effects of a 12-week low-starch diet on HOMA2B IR (Homeostatic Model As-sessment for Beta Cell Function Insulin Resistance) in overweight women using tele-health consultations. Methods: A prospective single arm intervention study was conducted among 14 overweight women aged 18-48 years with a body mass index (BMI) of 25-29,9 kg/m^2. Participants received weekly telehealth consultations via video conference with an endocrinologist and were prescribed a low-starch diet for 12 weeks. The dietary intervention focused on reducing the intake of high-starch foods, such as refined grains, potatoes, and bread, while promoting the consumption of non-starchy vegetables, lean protein, and healthy fats. HOMA2B IR, a widely used surrogate marker of insulin resistance, was measured at baseline and after 12 weeks. Results: After 12 weeks of the low-starch diet intervention, there was a significant reduction in HOMA2B IR in overweight women (Mean ± SD: Baseline HOMA2B IR data (2.126 ± 1.909) improved to 1.522 ± 1.468 at 12 weeks (p &amp;lt; 0.05)), indicating improved beta cell function and decreased insulin resistance. Participants also showed reductions in bodyweight, waist circumference, and fasting blood glucose levels. The compliance with the low starch diet was generally high. Conclusion: Our findings suggest that a 12-week low-starch diet administered through telehealth consultations may have positive effects on HOMA2B IR, as well as bodyweight and fasting blood glucose levels, in overweight women. These results highlight the potential of telehealth as a convenient and effective mode of delivering lifestyle interventions to improve metabolic health. More research with larger sample sizes and longer follow-up periods is warranted to confirm these findings and explore the long-term effects of telehealth-based interventions on metabolic health outcomes. Presentation: Saturday, June 17, 2023

SAT002 Liver-specific Loss Of The Nuclear Receptor Co-regulator ARGLU1 Protects Against Diet-induced Obesity In Female Mice Independent Of Food Intake And Energy Expenditure

Abstract Disclosure: S.B. Cash: None. L. Magomedova: None. R. Tsai: None. C.L. Cummins: None. Arginine and glutamate rich 1 (ARGLU1) has been shown to be a co-regulator for several nuclear receptors including ER, GR and the peroxisome proliferator-activated receptors (PPARs), which are key modulators of nutrient metabolism. We have previously reported that loss of ARGLU1 in the liver protects aged male mice against high-fat diet induced obesity and type 2 diabetes [1]. Here, we assessed the importance of ARGLU1 in lipid and carbohydrate metabolism in aged female mice and used indirect calorimetry to understand the metabolic basis of the resistance to weight gain observed with liver-specific loss of ARGLU1. Aged (11-month-old) female wildtype floxed-Arglu1 mice (Arglu1fl/fl) and liver-specific Arglu1-null mice (Arglu1LKO) were fed a high fat, high cholesterol diet (HFD, 42% calories from fat, TD.88137 Envigo) for 12-weeks (N=7-17). Female mice were housed in Promethion Metabolic Cages (Sable Systems) at room temperature for 5 days during which their food intake, water intake, physical activity, O2 consumption, and CO2 production were measured (N=5-7). Female mice were also subjected to a glucose tolerance test and insulin tolerance test (N=4-8). In agreement with our previous results in male Arglu1LKO mice [1], female Arglu1LKO mice were resistant to diet-induced obesity with final body weights compared to HFD-fed Arglu1fl/fl mice of 30.6 ± 0.9 g vs 35 ± 1 g (P&amp;lt;0.05). Likewise, female Arglu1LKO mice were more glucose tolerant and insulin tolerant compared to HFD-fed Arglu1fl/fl mice. The metabolic cage data showed no change in food intake, locomotor activity or energy expenditure between HFD-fed Arglu1fl/fl and Arglu1LKO mice when accounting for body mass as a covariate (ANCOVA, CalR). Surprisingly, HFD-fed female Arglu1LKO mice had significantly higher water intake compared to HFD-fed Arglu1fl/fl mice (P&amp;lt;0.02). These data support the conclusion that resistance to diet-induced obesity in Arglu1LKO mice is independent of sex. To our surprise, based on the metabolic cage data, we conclude that the mechanism by which Arglu1LKO mice are resistant to diet induced obesity is not due to enhanced energy expenditure or decreased food intake. Future studies will explore whether differential intestinal lipid absorption (independent of food intake) could account for the differences we observed in weight gain between the genotypes. [1] Magomedova, L., Tsai, R., &amp; Cummins, C. L. (2017, April). Hepatic Ablation of the Nuclear Receptor Coactivator, ARGLU1, Is Protective Against the Development of Type 2 Diabetes and Fatty Liver in High-Fat Diet Fed Mice. In 99th Annual Meeting of the Endocrine Society. Endocrine Society. Presentation: Saturday, June 17, 2023

Semen Quality and Reproductive Morphometry of Two Breeds of Cocks Fed Ficus Exasperate Leaf Meal and Vitamin C Supplemented Diets

The assessment of semen quality and reproductive morphometry of two breeds of cocks is based on the evaluation of sperm, the testicular and epididymal morphometry from the breeds of cocks. Two breeds of cocks (Noiler and Rhode Island Red) fed Ficus exasperata leaf meal and vitamin C supplemented diets were evaluated for the semen quality and reproductive morphometry. One hundred and forty-four birds were used for the experiment. The cocks were weighed randomly and assigned to four dietary treatments of six replicates with three cocks per replicate. The birds were fed their respective experimental diet for 12weeks, while feed and water were provided ad-libitum. The experiment was carried out using Factorial Design or a Statistical Experimental Design. The diets were divided into four treatments which the diet 1 was the control (basal diet), the diet 2 consists of 200mg/kg and vitamin C supplement, the diet 3 consists of Ficus exasperata and 1kg of basal diet and the diet 4 consists of 200mg/kg vitamin C with Ficus exasperata and 1kg of basal diet. The result showed that there is no significant (p&gt;0.05) different in the semen characteristics except the total sperm cell. It was thus concluded that Ficus exasperata leaf meal and vitamin C could be used in the diet without adverse effect on the quality of semen and reproductive morphology and function.

Effect of Moderate Malnutrition on thePharmacokinetics of Etoposide and Vincristine in Freshly Weaned Rats.

Moderate malnutrition is a common problem in young children. It is observed that severe malnutrition affects the pharmacokinetics of chemotherapy drugs in pediatric cancer patients, but moderate malnutrition is not well studied in this context. In this study, we aimed to understand how moderate malnutrition affects the pharmacokinetics of two chemotherapy drugs, etoposide and vincristine, using a murine model of early age moderate malnutrition. We developed a murine model of moderate childhood malnutrition by subjecting freshly weaned Sprague-Dawley rats to 8% protein diet for 8weeks. In two separate experiments, we administered etoposide and vincristine (N = 8 for etoposide and N = 12 for vincristine each in protein deficient and control groups) through tail vein injection for pharmacokinetics study. We found ~ 60% increase in area under the concentration-time curve (AUC) of etoposide in malnourished animals as compared to well-nourished animals. Furthermore, clearance, volume of distribution, and half-life were decreased by ~ 37, 53, and 24%, respectively, in malnourished animals. Pharmacokinetic parameters of vincristine showed only marginal differences between well-nourished and malnourished groups. Our results suggest that while moderate malnutrition significantly affects the pharmacokinetics of etoposide, pharmacokinetics of vincristine remain unchanged. Since chemotherapy drugs have a narrow therapeutic index, the difference in AUC observed in our study might explain the increased toxicity of etoposide in malnourished pediatric cancer patients. This brings forth a need for robust clinical studies to validate our findings and optimize dose for malnourished patients.

Abstract P390: E-value Over P-value And Its Adjustments: Improving Dna Methylation Analysis With An Application To Hypertension Studies

DNA methylation plays a crucial role in transcriptional regulation. Reduced representation bisulfite sequencing (RRBS) is a technique of increasing use for analyzing genome-wide methylation profiles. Many computational tools such as Metilene, MethylKit, BiSeq and DMRfinder have been developed to use RRBS data to detect differentially methylated regions (DMRs) that may be involved in epigenetic regulations of gene expression. For DMR detection tools, as for countless other medical literature applications, P-values and their adjustments are among the most widely reported statistics used to assess the statistical significance of biological findings. However, P-values are coming under increasing criticism related to their questionable accuracy and relatively high levels of false positive or negative indications. Here, we proposed a method to calculate E-value for DMR detection in RRBS data, which is defined as likelihood ratios falling into the null hypothesis over the entire parameter space. We also provided the corresponding R package ‘ metevalue ’ as a user-friendly interface to implement E-value calculations into various DMR detection tools. To evaluate the performance of E-value, we generated various RRBS benchmarking datasets using our simulator ‘ RRBSsim ’ with 8 samples in each experimental group. Our comprehensive benchmarking analyses showed that using E-value not only significantly improved accuracy, AUC and power, over that of P-value or adjusted P-value, but also reduced false discovery rates and Type I errors. To illustrate the utility of E-value, we applied it to identify DMRs in two real RRBS datasets. One was genome-wide DNA methylome and transcriptome of renal T lymphocytes from Dahl Salt Sensitive rats treated with high- or low-salt diets. The other was genome-wide DNA methylation and gene expression data of human arterioles from our clinical trial in which 10 subjects were placed on 2-week low-salt diet (1200-mg sodium/day). Compared to the classical adjusted P-value, the use of E-value detected biologically more relevant DMRs and improved the negative association between DNA methylation and gene expression.

High-fiber diet and rope-skipping benefit cardiometabolic health and modulate gut microbiota in young adults: A randomized controlled trial

Previous studies have shown that high intake of dietary fiber (DF) and efficient levels of physical activity are beneficial for cardiometabolic health in middle-aged and elderly populations with cardiometabolic disease. However, evidence from young adults with low cardiometabolic risk is lacking. This study aimed to investigate the effects of various interventions including a high-fiber (HF) diet and the rope-skipping (RS) exercise on cardiometabolic risk factors (CRFs) and the composition of the gut microbiota in young adults. A 12-week parallel-designed randomized controlled trial was conducted in undergraduates (n = 96), who were randomly assigned to the HF group (≥20 g/d DF), the RS group (2000 jumps/week), and the control (CON) group. Among the 84 people who completed the trial, measurements of anthropometric characteristics, biochemical parameters, and gut microbiota were taken at the beginning and end of the intervention. After the intervention, the RS exercise led to a significant decrease in the heart rate and triglyceride levels compared to the CON group (all P < 0.05), but there was no significant difference in CRFs between the HF and CON groups. When compared to baseline, the 12-week HF diet intervention resulted in an increase in fat-free mass, and a decrease in the percentage of body fat and waist circumference (all P < 0.05). With regard to gut microbiota alterations after intervention, we found that compared with the CON group, the relative abundance of Lactobacillus decreased significantly in both the HF group and the RS group, Muribaculaceae decreased in the RS group, and Eubacterium_coprostanoligenes_group decreased in the HF group (all P < 0.05). Finally, shifts in 7 metabolic pathways were detected in the RS group using predictive functional profiling, while only one pathway was altered in the HF group (all P < 0.05). In conclusion, the RS exercise improved body composition compared to the CON group in young adults, while the HF diet just enhanced CRFs in contrast to baseline. Furthermore, both RS and HF interventions altered Lactobacillus and various other gut microbiota. The results indicated that the HF diet and RS exercise could partly benefit cardiometabolic health and modulate gut microbiota in young adults. Trial registration: ClinicalTrials.gov, NCT04834687.

No Observed Difference in Inflammatory and Coagulation Markers Following Diets Rich in n-6 Polyunsaturated Fat vs Monounsaturated Fat in Adults With Untreated Hypercholesterolemia: A Randomized Trial

BackgroundInflammatory and prothrombotic responses are hallmark to the progression of cardiovascular disease and may be influenced by the type of dietary fat. Cottonseed oil (CSO) is rich in n-6 polyunsaturated fats and improves traditional cardiovascular disease risk factors such as cholesterol profiles. However, some clinicians are still hesitant to promote n-6 polyunsaturated fats consumption despite growing evidence suggesting they may not be independently pro-inflammatory. ObjectiveTo investigate the inflammatory and coagulation marker responses to an 8-week diet intervention rich in either CSO or olive oil (OO) (OO is rich in monounsaturated fat) in adults with untreated hypercholesterolemia. DesignThis was a secondary analysis of a parallel-arm randomized clinical trial with the main outcome of cholesterol measures. Participants/settingParticipants included in this analysis were 42 sedentary adults aged 30 to 75 years (62% women) in the Athens, GA, area, between May 2018 and June 2021, with untreated hypercholesterolemia or elevated blood lipids and body mass index >18.5. Hypercholesterolemia was defined as at least two blood lipid levels in a borderline undesirable/at risk range (total cholesterol level ≥180 mg/dL, low-density lipoprotein cholesterol level ≥110 mg/dL, high-density lipoprotein cholesterol level <50 mg/dL, or triglyceride level ≥130 mg/dL), or at least one in an undesirable range (total cholesterol level ≥240 mg/dL, low-density lipoprotein cholesterol level ≥160 mg/dL, high-density lipoprotein cholesterol level <40 mg/dL, or triglyceride level ≥200 mg/dL). InterventionParticipants were randomly assigned to either the CSO or OO group in a partial outpatient feeding trial. Meals from the study provided approximately 60% of their energy needs with 30% of energy needs from either CSO or OO for 8 weeks. Participants fulfilled their remaining energy needs with meals of their choosing. Main outcome measuresFasting plasma concentrations of inflammatory markers, including C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-1β were measured at baseline and 8 weeks. Markers of coagulation potential, including plasminogen activator inhibitor-1, and tissue factor were measured at the same time points. Statistical analyses performedRepeated measures linear mixed models were used with treatment and visit in the model for analyses of all biochemical markers. ResultsThere were no significant differences in fasting C-reactive protein (P = 0.70), tumor necrosis factor-α (P = 0.98), interleukin-6 (P = 0.21), interleukin-1β (P = 0.13), plasminogen activator inhibitor-1 (P = 0.29), or tissue factor (P = 0.29) between groups across the intervention. ConclusionsInflammation and coagulation marker responses to diets rich in CSO vs OO were not significantly different between groups, and neither group showed changes in these markers in adults with untreated hypercholesterolemia. This provides additional evidence suggesting that dietary n-6 polyunsaturated fats may not promote inflammation compared with monounsaturated fatty acids, even in adults at increased risk for cardiovascular disease.

Interactions between Mediterranean Diet Supplemented with Dairy Foods and the Gut Microbiota Influence Cardiovascular Health in an Australian Population.

The impact of a Mediterranean diet on the intestinal microbiome has been linked to its health benefits. We aim to evaluate the effects of a Mediterranean diet supplemented with dairy foods on the gut microbiome in Australians at risk of cardiovascular disease. In a randomised controlled cross-over study, 34 adults with a systolic blood pressure ≥120 mmHg and with risk factors for cardiovascular disease were randomly allocated to a Mediterranean diet with 3-4 daily serves of dairy foods (Australian recommended daily intake (RDI) of 1000-1300 mg per day (MedDairy)) or a low-fat (LFD) control diet. Between each 8-week diet, participants underwent an 8-week washout period. Microbiota characteristics of stool samples collected at the start and end of each diet period were determined by 16S rRNA amplicon sequencing. MedDairy-associated effects on bacterial relative abundance were correlated with clinical, anthropometric, and cognitive outcomes. No change in the overall faecal microbial structure or composition was observed with either diet (p > 0.05). The MedDairy diet was associated with changes in the relative abundance of several bacterial taxa, including an increase in Butyricicoccus and a decrease in Colinsella and Veillonella (p < 0.05). Increases in Butyricicoccus relative abundance over 8 weeks were inversely correlated with lower systolic blood pressure (r = -0.38, p = 0.026) and positively correlated with changes in fasting glucose levels (r = 0.39, p = 0.019), specifically for the MedDairy group. No significant associations were observed between the altered taxa and anthropometric or cognitive measures (p > 0.05). Compared to a low-fat control diet, the MedDairy diet resulted in changes in the abundance of specific gut bacteria, which were associated with clinical outcomes in adults at risk of CVD.

Nutritive/non-nutritive sweeteners and high fat diet contribute to dysregulation of sweet taste receptors and metabolic derangements in oral, intestinal and central nervous tissues.

Overconsumption of non-nutritive sweeteners is associated with obesity, whereas the underlying mechanisms remain controversial. This study aimed to investigate the effects of long-term consumption of nutritive or non-nutritive sweeteners with or without high fat diet on sweet taste receptor expression in nutrient-sensing tissues and energy regulation dependent on sweet-sensing. 50 Male Sprague-Dawley rats (140-160g) were assigned to 10 groups (n = 5/group). All received fructose at 2.5% or 10%, sucralose at 0.01% or 0.015% or water with a normal chow diet or high fat diet for 12weeks. Food and drink intake were monitored daily. Oral glucose tolerance test and intraperitoneal glucose tolerance test were performed at week 10 and 11 respectively. Serum was obtained for measurement of biochemical parameters. Tongue, duodenum, jejunum, ileum, colon and hypothalamus were rapidly removed to assess gene expression. Long-term consumption of sweeteners impaired glucose tolerance, increased calorie intake and body weight. A significant upregulation of sweet taste receptor expression was observed in all the four intestinal segments in groups fed 0.01% sucralose or 0.015% sucralose, most strikingly in the ileum, accompanied by elevated serum glucagon-like peptide-1 levels and up-regulated expression of sodium-dependent glucose cotransporter 1 and glucose transporter 2. A significant down-regulation in the tongue and hypothalamus was observed in groups fed 10% fructose or 0.015% sucralose, with alterations in hypothalamic appetite signals. The presence of high fat diet differentially modulates sweet taste perception in nutrient-sensing tissues. Long-term consumption of whether nutritive sweeteners or non-nutritive sweeteners combined with high fat diet contribute to dysregulation of sweet taste receptor expression in oral, intestinal and central nervous tissues.

Multiple micronutrient deficiencies alter energy metabolism in host and gut microbiome in an early-life murine model.

Micronutrients perform a wide range of physiological functions essential for growth and development. However, most people still need to meet the estimated average requirement worldwide. Globally, 2 billion people suffer from micronutrient deficiency, most of which are co-occurring deficiencies in children under age five. Despite decades of research, animal models studying multiple micronutrient deficiencies within the early-life period are lacking, which hinders our complete understanding of the long-term health implications and may contribute to the inefficacy of some nutritional interventions. Evidence supporting the Developmental Origins of Health and Disease (DOHaD) theory demonstrates that early-life nutritional deficiencies carry life-long consequences mediated through various mechanisms such as abnormal metabolic programming, stunting, altered body composition, and the gut microbiome. However, this is largely unexplored in the multiple micronutrient deficient host. we developed a preclinical model to examine undernutrition's metabolic and functional impact on the host and gut microbiome early in life. Three-week-old weanling C57BL/6N male mice were fed a low-micronutrient diet deficient in zinc, folate, iron, vitamin A, and vitamin B12 or a control diet for 4-weeks. Our results showed that early-life multiple micronutrient deficiencies induced stunting, altered body composition, impaired glucose and insulin tolerance, and altered the levels of other micronutrients not depleted in the diet within the host. In addition, functional metagenomics profiling and a carbohydrate fermentation assay showed an increased microbial preference for simple sugars rather than complex ones, suggestive of a less developed microbiome in the low-micronutrient-fed mice. Moreover, we found that a zinc-only deficient diet was not sufficient to induce these phenotypes, further supporting the importance of studying co-occurring deficiencies. Together, these findings highlight a previously unappreciated role of early-life multiple micronutrient deficiencies in shaping the metabolic phenome of the host and gut microbiome through altered glucose energy metabolism, which may have implications for metabolic disease later in life in micronutrient-deficient survivors.

The impact of liraglutide treatment on erectile function of the diabetic rats

Objectives: Glucagon like peptide-1 (GLP-1) is a hormone released from intestinal L-cells following nutrient consumption. It potentiates secretion of insulin from pancreatic beta-cells thus GLP-1 analogues are used for the treatment of type-2 diabetes mellitus( T2DM). This study aims to evaluate impact of GLP-1 receptor agonist liraglutide on erectile function of diabetic rats. Methods: Male Sprague-Dawley rats (n = 30, 13-weeks old, 240-335 gr) were fed with fatty diet for 2-weeks and divided into 3 groups (n = 10 each). The rats in the first group served as controls (Group C) whereas the rats in the remaining two groups were injected with streptozocin and became T2DM for forming diabetic group (Group D) and treatment group (Group DT). Rats in group D received citrate buffer injections whereas rats in the group DT received liraglutide injections (0.3 mg/kg/12h) subcutaneously. Erectile functions of all rats were evaluated with intracavernosal pressure (ICP)/mean arterial pressure (MAP) measurements. Moreover, plasma sex hormone levels (Testosterone, FSH, LH) were measured and histological assessment of midpenile tissue were performed (Collagen-Type-IV, rat epithelial antigen-1, nNOS). Results: Maximum ICP/MAP ratios were 0.790 ± 0.164, 0.263 ± 0.139 and 0.652 ± 0.131 in Group C, Group D and Group DT. Although mean ICP/MAP ratios were similar in Group C and Group DT (p = 0.076), mean ICP/MAP ratio was significantly lower in Group D (p &amp;lt; 0.001). Testosterone and FSH results were significantly lower in the Group D as well (p = 0.001). Histological analyses revealed that nNOS (p &amp;lt; 0.001), rat epithelial antigen-1 (p = 0.016) and muscle/collagen ratio (p = 0.015) were also lower in Group D, compared with the other groups. Conclusions: GLP-1 receptor agonist liraglutide demonstrated protective effects on the erectile tissues of the diabetic rats. Clinical trials are required to confirm if liraglutide treatment has similar beneficial effects on men who have T2DM.

P16-001-23 Subjective Appetite Responses to a 4-week High-Fiber Diet

P16-001-23 Subjective Appetite Responses to a 4-week High-Fiber Diet

P16-024-23 Consuming a Low-Carbohydrate/High-Protein Diet for 8Weeks Altered Serum Metabolome in Individuals With Chronic Spinal Cord Injury

P16-024-23 Consuming a Low-Carbohydrate/High-Protein Diet for 8Weeks Altered Serum Metabolome in Individuals With Chronic Spinal Cord Injury