Diet-induced Changes Research Articles

Metabolic dysfunction induced by HFD + L-NAME preferentially affects hippocampal mitochondria, impacting spatial memory in rats.

High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.

Effects of dietary energy level on antioxidant capability, immune function and rectal microbiota in late gestation donkeys.

This study investigated the effects of dietary energy level on the antioxidant capability, immune function, and rectal microbiota in donkey jennets during the last 60 days of gestation. Fifteen pregnant DeZhou donkeys with age of 6.0 ± 0.1 years, body weight of 292 ± 33 kg, parity of 2.7 ± 0.1 parities and similar expected date of confinement (74 ± 4 days) were randomly allocated to three groups and feed three diets: high energy (10.92 MJ/kg, H), medium energy (10.49 MJ/kg, M), and low energy (9.94 MJ/kg, L). The serum activity of catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in group M was significantly higher, whereas the concentrations of malondialdehyde (MDA), interleukin 1 (IL-1), IL-2, and IL-6 were lower than those recorded for groups H and L (p ≤ 0.05). The dietary energy level significantly affected rectal microbial community structure in the jennet donkeys 35 days and 7 days before the parturition (p ≤ 0.05). The abundances of norank_f_norank_o_Coriobacteriales genus was significantly higher (p ≤ 0.05) in group H, and the abundances of norank_f_norank_o_Mollicutes_RF39 and the Candidatus_Saccharimonas were higher in group L (p ≤ 0.05). The abundance of Fibrobacter in group M was significantly increased (p ≤ 0.05). The abundance of norank_f_norank_o_Coriobacteriales was positively correlated with average daily gain (ADG) and tumor necrosis factor-α (TNF-α) concentrations (p ≤ 0.05). The abundance of norank_f_norank_o_Mollicutes_RF39 was positively correlated with IL-2 and IL-6 concentrations. The abundance of Candidatus_Saccharimonas was positively correlated with CAT, T-SOD and GSH-Px activities (p ≤ 0.05). The abundance of Fibrobacter was positively correlated with CAT and T-SOD activities (p ≤ 0.05), but negatively correlated with IL-2 concentration (p ≤ 0.05). In conclusion, an appropriate dietary with an energy content of 10.49 MJ/kg for jennet donkeys during late gestation increased the prenatal antioxidant capacity, reduced inflammatory cytokines, and promoted fetal growth, and these changes were related to diet-induced changes in rectal microbiota compositions.

Sex modulates the diet-induced changes to the plasma lipidome in a rat model of cardiorespiratory fitness

ObjectiveIndividuals with higher intrinsic cardiorespiratory fitness (CRF) experience decreased rates of cardiometabolic disease and mortality, and high CRF is associated with increased utilization of fatty acids (FAs) for energy. Studies suggest a complex relationship between CRF, diet, and sex with health outcomes, but this interaction is understudied. We hypothesized that FA utilization differences by fitness and sex could be detected in the plasma metabolome when rats or humans were fed a high carbohydrate (HC) or high fat (HF) diet. MethodsMale and female rats selectively bred for low (LCR) and high (HCR) CRF were fed a chow diet or a sucrose-free HF (45 % fat) or HC (10 % fat) diet. Plasma samples were collected at days 0, 3, and 14. Human plasma data was collected from male and female participants who were randomized into a HC or HF diet for 21 days. Samples were analyzed using liquid chromatography-mass spectrometry and regression statistics were used to quantify the effect of diet, CRF, and sex on the lipidome. ResultsIn rats, the baseline lipidome is more significantly influenced by sex than by CRF, especially as elevated diglycerides, triglycerides, phosphatidylcholines, and lysophosphatidylcholines in males. A dynamic response to diet was observed 3 days after diet, but after 14 days of either diet, the lipidome was modulated by sex with a larger effect size than by diet. Data from the human study also suggests a sex-dependent response to diet with opposite directionality of affect compared to rats, highlighting species-dependent responses to dietary intervention.

Early time-restricted carbohydrate consumption vs conventional dieting in type 2 diabetes: a randomised controlled trial

Aims/hypothesisEarly time-restricted carbohydrate consumption (eTRC) is a novel dietary strategy that involves restricting carbohydrate-rich food intake to the morning and early afternoon to align with circadian variations in glucose tolerance. We examined the efficacy, feasibility and safety of eTRC in individuals with type 2 diabetes under free-living conditions.MethodsIn this randomised, parallel-arm, open label, controlled trial, participants with type 2 diabetes and overweight/obesity (age 67.2±7.9 years, 47.8% women, BMI 29.4±3.7 kg/m2, HbA1c 49±5 mmol/mol [6.6±0.5%]) were randomised, using computer-generated random numbers, to a 12 week eTRC diet or a Mediterranean-style control diet with matched energy restriction and macronutrient distribution (50% carbohydrate, 30% fat and 20% protein). The primary outcome was the between-group difference in HbA1c at 12 weeks. Body composition, 14 day flash glucose monitoring and food diary analysis were performed every 4 weeks. Mixed meal tolerance tests with mathematical beta cell function modelling were performed at baseline and after 12 weeks.ResultsTwelve (85.7%) participants in the eTRC arm and 11 (84.6%) participants in the control arm completed the study, achieving similar reductions in body weight and fat mass. The two groups experienced comparable improvements in HbA1c (−3 [−6, −0.3] mmol/mol vs −4 [−6, −2] mmol/mol, corresponding to −0.2 [−0.5, 0]% and −0.3 [−0.5, −0.1]%, respectively, p=0.386), fasting plasma glucose, flash glucose monitoring-derived glucose variability and mixed meal tolerance test-derived glucose tolerance, insulin resistance, insulin clearance and plasma glucagon levels, without changes in model-derived beta cell function parameters, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and non-esterified fatty acid levels. The two diets similarly reduced liver function markers and triglyceride levels, being neutral on other cardiometabolic and safety variables. In exploratory analyses, diet-induced changes in body weight and glucometabolic variables were not related to the timing of carbohydrate intake.Conclusions/interpretationThe proposed eTRC diet provides a feasible and effective alternative option for glucose and body weight management in individuals with type 2 diabetes, with no additional metabolic benefits compared with conventional dieting.Trial registrationClinicalTrials.gov NCT05713058FundingThis study was supported by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the Italian Society of Diabetology (SID).Graphical

Mdivi1 ameliorates mitochondrial dysfunction in non-alcoholic steatohepatitis by inhibiting JNK/MFF signaling.

Mitochondrial dysfunction plays a crucial role in the progression of non-alcoholic steatohepatitis (NASH). Mitochondrial division inhibitor 1 (Mdivi1) is a potential inhibitor of dynamin-related protein (Drp1) and mitochondrial fission. However, the therapeutic effect of Mdivi1 against NASH and its underlying molecular mechanisms remain unclear. In this study, we established mouse models of NASH by inducing high-fat/high-cholesterol (HFHC) or methionine- and choline-deficient (MCD) diets and treated the animals with 5mg/kg/day Mdivi1 or placebo. Treatment with Mdivi1 significantly alleviated diet-induced fatty liver phenotypes, including increased liver weight/body weight ratio, insulin resistance, hepatic lipid accumulation, steatohepatitis, and liver injury. Furthermore, Mdivi1 treatment suppressed HFHC or MCD diet-induced changes in the expression of genes related to lipid metabolism and inflammatory cytokines. Additionally, Mdivi1 reduced macrophage infiltration in the injured liver and promoted polarization of macrophages towards the M1 phenotype. At the molecular level, Mdivi1 attenuated mitochondrial fission by reducing Drp1 activation and expression, thereby decreasing mitochondrial reactive oxygen species accumulation and mitochondrial DNA damage. Moreover, Mdivi1-treated mice exhibited elevated levels of phosphorylated-c-Jun N-terminal kinase (p-JNK), mitochondrial fission factor (MFF), cleaved caspase 3 protein, and TUNEL-positive cell expression in the liver, suggesting that Mdivi1 might ameliorate mitochondrial dysfunction and reduce hepatocyte apoptosis by inhibiting the JNK/MFF pathway. Collectively, Mdivi1 protected against diet-induced NASH by restoring mitochondrial homeostasis and function, potentially through its inhibitory effect on the JNK/MFF pathway. Consequently, further investigation of Mdivi1 as a promising drug for NASH treatment is warranted.

Longitudinal associations of macronutrient and micronutrient intake with plasma kynurenines in colorectal cancer survivors up to 12 months posttreatment

BackgroundThe tryptophan-kynurenine pathway is increasingly recognized to play a role in health-related quality of life (HRQoL) after cancer. Because tryptophan is an essential amino acid, and vitamins and minerals act as enzymatic cofactors in the tryptophan-kynurenine pathway, a link between diet and kynurenines is plausible. ObjectivesThis study aimed to investigate the longitudinal associations of macronutrient and micronutrient intake with metabolites of the kynurenine pathway in colorectal cancer (CRC) survivors up to 12 mo posttreatment. MethodsIn a prospective cohort of stage I–III CRC survivors (n = 247), repeated measurements were performed at 6 wk, 6 mo, and 12 mo posttreatment. Macronutrient and micronutrient intake was measured by 7-d dietary records. Plasma concentrations of tryptophan and kynurenines were analyzed using liquid chromatography tandem mass spectrometry (LC/MS-MS). Longitudinal associations were analyzed using linear mixed models adjusted for sociodemographic, clinical, and lifestyle factors. ResultsAfter adjustment for multiple testing, higher total protein intake was positively associated with kynurenic acid (KA) (β as standard deviation [SD] change in KA concentration per 1 SD increase in total protein intake: 0.12; 95% CI: 0.04, 0.20), xanthurenic acid (XA) (standardized β: 0.22; 95% CI: 0.11, 0.33), 3-hydroxyanthranilic acid (HAA) (standardized β: 0.15; 95% CI: 0.04, 0.27) concentrations, and the kynurenic acid-to-quinolinic acid ratio (KA/QA) (standardized β: 0.12; 95% CI: 0.02,0.22). In contrast, higher total carbohydrate intake was associated with lower XA concentrations (standardized β: −0.18; 95% CI: −0.30, −0.07), a lower KA/QA (standardized β: −0.23; 95% CI: −0.34, −0.13), and a higher kynurenine-to-tryptophan ratio (KTR) (standardized β: 0.20; 95% CI: 0.10, 0.30). Higher fiber intake was associated with a higher KA/QA (standardized β: 0.11; 95% CI: 0.02, 0.21) and a lower KTR (standardized β: −0.12; 95% CI: −0.20, −0.03). Higher total fat intake was also associated with higher tryptophan (Trp) concentrations (standardized β: 0.18; 95% CI: 0.06, 0.30) and a lower KTR (standardized β: −0.13; 95% CI: −0.22, −0.03). For micronutrients, positive associations were observed for zinc with XA (standardized β: 0.13; 95% CI: 0.04, 0.21) and 3-hydroxykynurenine (HK) (standardized β: 0.12; 95% CI: 0.03, 0.20) concentrations and for magnesium with KA/QA (standardized β: 0.24; 95% CI: 0.13, 0.36). ConclusionsOur findings show that intake of several macronutrients and micronutrients is associated with some metabolites of the kynurenine pathway in CRC survivors up to 12 mo posttreatment. These results may be relevant for enhancing HRQoL after cancer through potential diet-induced changes in kynurenines. Further studies are necessary to confirm our findings.

FRI288 Single-Cell Transcriptomics Identifies Pituitary Gland Cell Type Population Changes In Diet Induced Obesity

Abstract Disclosure: R.E. Ruggiero-Ruff: None. B. Le: None. N. Lainez: None. D. Coss: None. Obesity is a worldwide growing public health concern, with a current prevalence of 43% in the United States and projected future increase. Obesity is associated with type 2 diabetes, cardiovascular disease, stroke, and endocrine abnormalities. The pituitary gland is the master gland that responds to metabolic perturbations and regulates homeostasis via hormone secretion. Thyrotrophic, gonadotropic, somatotropic, lactotropic and corticotropic dysfunctions may occur as a consequence of obesity and perpetuate pathophysiologic conditions since pituitary hormones regulate metabolic function in return. Previous work from our lab determined that mice fed high fat diet have reduced levels of gonadotropin hormones, indicating that diet-induced obesity may play a role in pituitary hormone production. We postulate that diet-induced obesity alters the pituitary transcriptome and/or select population changes. To determine the effect of diet-induced obesity on pituitary gland population plasticity, we performed single-cell RNA-sequencing (scRNA-seq) of pituitary glands from control and high-fat diet-fed mice and characterized population changes and gene expression changes in each population. While gonadotrope population changes levels of gene expression that results in the lower gonadotropin levels, somatotrope and lactotrope populations, on the other hand, change at the population level with alterations in the cell numbers that result in altered levels of growth hormone and prolactin in the circulation. In summary, we defined diet-induced changes in pituitary hormone production and population shifts that may play a role in altered hormone production in obese patients and consequently dysregulation of homeostasis. Presentation: Friday, June 16, 2023

Diet-induced changes in functional disability are mediated by fatigue in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES randomized parallel-arm trial.

People with multiple sclerosis (MS) often report dietary modifications; however, evidence on functional outcomes remains sparse. Evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets on functional disability among people with relapsing-remitting MS. Baseline-referenced MS functional composite (MSFC) scores were calculated from nine-hole peg-test (NHPT), timed 25-foot walk, and oral symbol digit modalities test (SDMT-O) collected at four study visits: (a) run-in, (b) baseline, (c) 12 weeks, and (d) 24 weeks. Participants were observed at run-in and then randomized at baseline to either the Swank (n = 44) or Wahls (n = 43) diets. Among the Swank group, MSFC scores significantly increased from -0.13 ± 0.14 at baseline to 0.10 ± 0.11 at 12 weeks (p = 0.04) and 0.14 ± 0.11 at 24 weeks (p = 0.02). Among the Wahls group, no change in MSFC scores was observed at 12 weeks from 0.10 ± 0.11 at baseline but increased to 0.28 ± 0.13 at 24 weeks (p = 0.002). In both groups, NHPT and SDMT-O z-scores increased at 24 weeks. Changes in MSFC and NHPT were mediated by fatigue. Both diets reduced functional disability as mediated by fatigue. Clinicaltrials.gov Identifier: NCT02914964.

Evaluation of a hepatic biomarker of nutritional imbalance in juvenile red drum (Sciaenops ocellatus) fed 60% soybean meal-based diets using NMR-based metabolomics

A 12-week feeding trial with juvenile red drum (Sciaenops ocellatus) fed high-soybean meal (SBM) diets was conducted to investigate a putative biomarker of nutritional imbalance, N-formimino-L-glutamate (FIGLU). Three fishmeal-free, 60% SBM pelleted diets (named B12, Fol, and Met, respectively) were tested to evaluate the effects on growth performance and tissue metabolite profiles of supplementation of vitamin B12 (0.012 mg/kg), folate (10 mg/kg), methionine (1 g/kg) respectively, above basal supplementation levels. A fourth SBM-based diet (named B12/Fol/Met) was formulated with a combination of B12, folate, and methionine to attain the above-mentioned target concentrations. A fifth 60% SBM diet (named FWS) with methionine supplementation (1 g/kg above basal supplementation levels), enriched with taurine, lysine and threonine as well as minerals, was also tested. This diet contained formulation targets and additives which have allowed for replacing fishmeal with plant proteins in rainbow trout feeds. Control diets included a fishmeal-based diet (named FM), an unsupplemented basal 60% SBM diet (named SBM60), and a “natural” diet (named N) made up of equal parts of fish (cigar minnows), squid and shrimp as a positive reference for growth performance. Formulated feeds contained approximately 37% total crude protein, approximately 14% total crude lipid and were energetically balanced. Standard growth performance metrics were measured, and tissues (liver, muscle) were collected at week 12 to evaluate diet-induced metabolic changes using nuclear magnetic resonance (NMR)-based metabolomics. Our results show that the FWS diet outperformed all other SBM diets and the FM diet under all performance metrics (P < 0.05). FIGLU was not detected in fish fed the N diet but was detected in those fed the SBM diets and the FM diet. Fish fed the FWS diet and the Met diet showed lower hepatic levels of FIGLU compared with the other SBM-based diets (P < 0.05), suggesting that among the different supplementation regimes, methionine supplementation was associated with lower FIGLU levels. The FWS diet produced tissue metabolite profiles that were more similar to those of fish fed the N diet. Based on our results, the FWS diet constitutes a promising SBM-based alternative diet to fishmeal for red drum.

Paternal high-fat diet altered SETD2 gene methylation in sperm of F0 and F1 mice

Paternal high-fat diet (HFD) can alter the epigenetics of sperm DNA, resulting in the transmission of obesity-related traits to the offspring. Previous studies have mainly focused on the HFD-induced changes in DNA methylation of imprinted genes, overlooking the potential involvement of non-imprinted genes in this process. SETD2, an important epigenetically-regulated gene known for its response to environmental stress, remains poorly understood in the context of high-fat diet-induced epigenetic changes. Here we examined the effect of obesity from a HFD on paternal SETD2 expression and methylation in sperm, and embryos at the blastocyst stage and during subsequent development, to determine the alteration of SETD2 in paternal intergenerational and transgenerational inheritance. The result showed that mice fed with HFD for two months had significantly increased SETD2 expression in testis and sperm. The paternal HFD significantly altered the DNA methylation level with 20 of the 26 CpG sites being changed in sperm from F0 mice. Paternal high-fat diet increased apoptotic index and decreased total cell number of blastocysts, which were closely correlated with DNA methylation level of sperm. Out of the 26 CpG sites, we also found three CpG sites that were significantly changed in the sperm from F1 mice, which meant that the methylation changes at these three CpG sites were maintained.In conclusion, we found that paternal exposure to an HFD disrupted the methylation pattern of SETD2 in the sperm of F0 mice and resulted in perturbed SETD2 expression. Furthermore, the paternal high-fat diet influenced embryo apoptosis and development, possibly through the SETD2 pathway. The altered methylation of SETD2 in sperm induced by paternal HFD partially persisted in the sperm of the F1 generation, highlighting the role of SETD2 as an epigenetic carrier for paternal intergenerational and transgenerational inheritance.

Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases.

Zinc is an essential micronutrient that is critical for many physiological processes, including glucose metabolism, regulation of inflammation, and intestinal barrier function. Further, zinc dysregulation is associated with an increased risk of chronic inflammatory diseases such as type II diabetes, obesity, and inflammatory bowel disease. However, whether altered zinc status is a symptom or cause of disease onset remains unclear. Common symptoms of these three chronic diseases include the onset of increased intestinal permeability and zinc dyshomeostasis. The specific focus of this work is to investigate how dietary sources of intestinal permeability, such as high sucrose consumption, impact transporter-mediated zinc homeostasis and subsequent zinc-dependent physiology contributing to disease development. We used in vivo subchronic sucrose treatment, ex vivo intestinal organoid culture, and in vitro cell systems. We analyze the alterations in zinc metabolism and intestinal permeability and metabolic outcomes. We found that subchronic sucrose treatment resulted in systemic changes in steady-state zinc distribution and increased 65Zn transport (blood-to-intestine) along with greater ZIP14 expression at the basolateral membrane of the intestine. Further, sucrose treatment enhanced cell survival of intestinal epithelial cells, activation of the EGFR-AKT-STAT3 pathway, and intestinal permeability. Our work suggests that subchronic high sucrose consumption alters systemic and intestinal zinc homeostasis linking diet-induced changes in zinc homeostasis to the intestinal permeability and onset of precursors for chronic disease.

Burden and trends of stroke attributable to dietary risk factors from 1990 to 2019 in the Belt and Road Initiative countries: an analysis from the global burden of disease study 2019.

This study aimed to compare the burden and trends of stroke attributed to dietary risk factors in the Belt and Road ("B&R") countries from 1990 to 2019. The 2019 Global Burden of Disease (GBD) Study was used to gather information on the burden of stroke attributable to dietary risk factors. Numbers and age-standardized rates (ASRs) of deaths, disability-adjusted life years (DALYs) were determined in 1990 and 2019 among the "B&R" countries. The average annual percent change (AAPC) was used to analyze the temporal trends of diet-induced stroke DALYs from 1990 to 2019 and in the final decade (2010-2019) by Joinpoint regression analysis. In 2019, the absolute number of stroke deaths and DALYs attributable to dietary risk factors were 671,872 cases (95% UI 436,354-937,093) and 1.67 million cases (95% UI 1.15-2.24) in China. We found geographical differences in mortality and DALYs of diet-attributable stroke among member countries, with Bulgaria, Hungary and Serbia being the three highest countries in 1990, Bulgaria, North Macedonia and Montenegro in Central Asia in 2019. The ASRs of diet-induced stroke mortality and DALYs were generally declining in most member states from 1990 to 2019, however, the corresponding metrics in Mongolia remained high. The fastest decline in ASR of mortality and DALYs for diet-induced stroke was seen in Estonia, Eastern Europe, with AAPC values of -7.09% (95%CI: -7.72, -6.46%) and - 6.62% (95%CI: -7.20, -6.03%), respectively. We noted a substantial downward trend in ASR of mortality and DALYs from diet-induced stroke changes in the final decade (2010-2019) for most member states. The ASR of DALYs for diet-induced stroke decreased greater in females than in males. For those aged 50-74, the DALYs for stroke due to dietary risk factors in all other member countries of the "B&R" showed a decreasing trend, except for the Philippines, which rose (AAPC = 2.13, 95%CI: 1.40-2.87%) and Turkmenistan, which remained stable (AAPC = 0.05, 95%CI: -0.43-0.33%). The burden of diet-induced stroke varies substantially across "B&R" countries and threaten public health, relevant evidence-based policies and interventions should be adopted to address the future burden of stroke in "B&R" countries through extensive collaboration.

Diet-Related Lipidomic Signatures and Changed Type 2 Diabetes Risk in a Randomized Controlled Feeding Study With Mediterranean Diet and Traditional Chinese or Transitional Diets.

Few trials studied the links of food components in different diets with their induced lipidomic changes and related metabolic outcomes. Thus, we investigated specific lipidomic signatures with habitual diets and modified diabetes risk by using a trial and a cohort. We included 231 Chinese with overweight and prediabetes in a randomized feeding trial with Mediterranean, traditional, or transitional diets (control diet) from February to September 2019. Plasma lipidomic profiles were measured at baseline, third month, and sixth month by high-throughput targeted liquid chromatography-mass spectrometry. Associations of the identified lipids with habitual dietary intakes were examined in another lipidomic database of a Chinese cohort (n = 1,117). The relationships between diet-induced changes of lipidomic species and diabetes risk factors were further investigated through both individual lipids and relevant modules in the trial. Out of 364 lipidomic species, 26 altered across groups, including 12 triglyceride (TAG) fractions, nine plasmalogens, four phosphatidylcholines (PCs), and one phosphatidylethanolamine. TAG fractions and PCs were associated with habitual fish intake while plasmalogens were associated with red meat intake in the cohort. Of the diet-related lipidomic metabolites, 10 TAG fractions and PC(16:0/22:6) were associated with improved Matsuda index (β = 0.12 to 0.42; PFDR < 0.030). Two plasmalogens were associated with deteriorated fasting glucose (β = 0.29 to 0.31; PFDR < 0.014). Similar results were observed for TAG and plasmalogen related modules. These fish- and red meat-related lipidomic signatures sensitively reflected different diets and modified type 2 diabetes risk factors, critical for optimizing dietary patterns.

How the Oviduct Lipidomic Profile Changes over Time after the Start of an Obesogenic Diet in an Outbred Mouse Model.

We investigated whether a high-fat/high-sugar (HF/HS) diet alters the lipidomic profile of the oviductal epithelium (OE) and studied the patterns of these changes over time. Female outbred Swiss mice were fed either a control (10% fat) or HF/HS (60% fat, 20% fructose) diet. Mice (n = 3 per treatment per time point) were sacrificed and oviducts were collected at 3 days and 1, 4, 8, 12 and 16 weeks on the diet. Lipids in the OE were imaged using matrix-assisted laser desorption ionisation mass spectrometry imaging. Discriminative m/z values and differentially regulated lipids were determined in the HF/HS versus control OEs at each time point. Feeding the obesogenic diet resulted in acute changes in the lipid profile in the OE already after 3 days, and thus even before the development of an obese phenotype. The changes in the lipid profile of the OE progressively increased and became more persistent after long-term HF/HS diet feeding. Functional annotation revealed a differential abundance of phospholipids, sphingomyelins and lysophospholipids in particular. These alterations appear to be not only caused by the direct accumulation of the excess circulating dietary fat but also a reduction in the de novo synthesis of several lipid classes, due to oxidative stress and endoplasmic reticulum dysfunction. The described diet-induced lipidomic changes suggest alterations in the OE functions and the oviductal microenvironment which may impact crucial reproductive events that take place in the oviduct, such as fertilization and early embryo development.

Impact of transgenerational host switch on gut bacterial assemblage in generalist pest, Spodoptera littoralis (Lepidoptera: Noctuidae).

Diet composition is vital in shaping gut microbial assemblage in many insects. Minimal knowledge is available about the influence of transgenerational diet transition on gut microbial community structure and function in polyphagous pests. This study investigated transgenerational diet-induced changes in Spodoptera littoralis larval gut bacteriome using 16S ribosomal sequencing. Our data revealed that 88% of bacterial populations in the S. littoralis larval gut comprise Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. The first diet transition experiment from an artificial diet (F0) to a plant diet (F1), cabbage and cotton, caused an alteration of bacterial communities in the S. littoralis larval gut. The second transgenerational diet switch, where F1 larvae feed on the same plant in the F2 generation, displayed a significant variation suggesting further restructuring of the microbial communities in the Spodoptera larval gut. F1 larvae were also challenged with the plant diet transition at the F2 generation (cabbage to cotton or cotton to cabbage). After feeding on different plant diets, the microbial assemblage of F2 larvae pointed to considerable differences from other F2 larvae that continued on the same diet. Our results showed that S. littoralis larval gut bacteriome responds rapidly and inexplicably to different diet changes. Further experiments must be conducted to determine the developmental and ecological consequences of such changes. Nevertheless, this study improves our perception of the impact of transgenerational diet switches on the resident gut bacteriome in S. littoralis larvae and could facilitate future research to understand the importance of symbiosis in lepidopteran generalists better.

Modulating the Human Gut Microbiota through Hypocaloric Balanced Diets: An Effective Approach for Managing Obesity.

This study aimed to investigate the effects of a hypocaloric balanced diet (HBD) on anthropometric measures and gut microbiota of 43 people with obesity. Fecal samples were collected from the study subjects at weeks 0 and 12, and a detailed analysis of gut microbiota was performed using 16S rRNA gene sequencing. By comparing anthropometric measures and microbiota changes in subjects before and after the HBD intervention, we revealed the potential effects of HBD on weight loss and gut microbiota. Our results indicated that the HBD resulted in a significant decrease in body mass index (BMI), and most of the physiological indicators were decreased to a greater degree in the effective HBD group (EHBD, weight loss ≥ 5%) than in the ineffective HBD group (IHBD, weight loss < 5%). The HBD intervention also modified the gut microbiota of the subjects with obesity. Specifically, Blautia, Lachnoclostridium, Terrisporobacter, Ruminococcus (R. torques, R. gnavus), and Pseudomonas were significantly reduced. In addition, we employed machine learning models, such as XGBRF and GB models, to rank the importance of various features and identified the top 10 key bacterial genera involved. Gut microbiota co-occurrence networks showed the dominance of healthier microbiota following successful weight loss. These results suggested that the HBD intervention enhanced weight loss, which may be related to diet-induced changes in the gut microbiota.

O74 Diet-induced changes in rumen epimural microbiota structure and predicted metabolic pathways in dairy goats

O74 Diet-induced changes in rumen epimural microbiota structure and predicted metabolic pathways in dairy goats

The effect of Pauttika honey and Orlistat on Histological Evaluations of Liver, Kidney and Adipose tissue in high-fat diet-induced Obesity in Charles Foster male rats

Background: Honey's weight-reducing, hypoglycemic, hypolipidemic, and hepatoprotective properties have been demonstrated. Orlistat, a FDA-approved medicine for obesity control, have adverse effects. Honey is a rich source of nutrients with antiobesity (Medohara) and sacrificant (lekhan) qualities, which help to reduce Pitta, Kapha, and Medas; is suggested in diabetic control. In this study, Pauttika honey is studied against biochemical markers and histological manifestations in visceral organs of high-fat diet-induced obese Charles Foster rats. No research was identified on the effect of Pauttika honey (a specific kind of honey described in Ayurveda) on obese rats' liver, kidney, and adipose tissues. An article on the biochemical analysis of this honey (new and old ) has been already published. Objective: Evaluate the effects of Pauttika honey and Orlistat on high-fat diet-induced fatty changes in obese Charles Foster rats. Methods: This study examines male Charles Foster rat histopathological alterations. 24 male Charles Foster rats with a mean weight of 181±15gm were divided into four groups of six. High-fat diets (HFD) for 8 weeks caused obesity in three groups. After that, Pauttika honey mixed with equal amounts of water (Madudaka) and Orlistat were given to two groups for 6 weeks. The HFD was maintained throughout the experiment, except in the NC group, which ate standard chow. On the last day of the 14th week, the animals were sacrificed and the Liver, kidney, heart, spleen, and lungs were weighed. The liver, kidney, and adipose tissues were preserved in 10% formalin for histopathology. Results: Rats’ relative organ weight (ROW) showed no significant alterations. Histology of liver tissues showed micro and macro steatosis and ballooning degeneration in the HFD group, while Pauttika honey and orlistat both showed improvement in fatty changes but it was better in the Pauttika group. Kidney and adipose tissues showed no morphological or structural abnormalities. Conclusion: This study shows that Pauttika honey mixed with water (Madudaka) protects the livers of obese rats. Histology suggests Pauttika honey is efficacious and safer than Orlistat for HFD-induced obesity.

1683-P: High-Fat Diet Downregulates CREG1 in the Liver via DNA Methylation

CREG1 is an endosomal-lysosomal protein which is highly expressed in the liver. Hepatocyte-specific deletion of Creg1 in mice causes insulin resistance and elevated glycemia. To test if CREG1 is nutritionally regulated, we fed mice for 10 weeks with a high-fat diet (HFD) which progressively downregulated CREG1 in the liver at both protein and mRNA levels. The CREG1 expression was restored after switch back to a standard chow diet for two weeks. The diet-induced CREG1 changes negatively correlated with blood glucose levels. Sequence analysis revealed enrichment of CpG islands in exon 1 of both human and mouse CREG1 genes. To test if methylation of these CpG islands contributes to HFD-induced CREG1 reduction, we fed mice with a HFD for 10 weeks and treated them with the DNA methyltransferase inhibitor 5-aza-deoxycytidine, which reversed HFD-induced CREG1 downregulation in the liver. At the cellular level, overload of cultured human hepatocytes with fatty acids reduced CREG1 expression, and this was reversed by inhibiting DNA methylation. Furthermore, removal of all CpG islands in the first exon with sense mutations abolished lipid overload-induced CREG1 downregulation. These results suggest that HFD downregulates CREG1 via DNA methylation of the CpG islands in the first exon. It would be interesting to test if CREG1 reduction mediates HFD-induced insulin resistance. Disclosure Y.Qi: None. J.Liu: None. J.C.Chao: None. S.A.Rahimi: None. L.Y.Lee: Speaker's Bureau; Abbott. S.Li: None. Funding Rutgers Biomedical and Health Sciences

Diet-induced changes in fecal microbiota composition and diversity in dogs (Canis lupus familiaris): A comparative study of BARF-type and commercial diets

BackgroundDiet is known to strongly modulate the composition of the gut microbiota, thereby affecting health conditions and disease. Natural BARF-type and commercial diets have been used for feeding pets (e.g. dogs and cats) promoting changes in the canine microbiota in terms of abundance, richness, and diversity that may favor certain metabolic processes and resistance to certain infectious agents. Therefore, the present study sought to identify microbiota changes in dogs fed with a BARF-type diet versus dogs fed with a commercial diet by sequencing the V4 region of the 16S rRNA gene. MethodsThe microbiota of dogs fed with the BARF-diet (n = 20) and commercial-diet (n = 26) was studied using fecal samples. A metabarcoding strategy was employed by sequencing the V4 hypervariable region of the 16S rRNA gene using the Illumina HiSeq platform. DADA2 was used to assess the quality profile of the reads and to determine the core sample inference algorithm of the reads to infer amplicon sequence variants (ASVs). The taxonomic assignment was performed using sequences from the Silva v138 formatted reference database. The microbial diversity analysis was performed using the R package Phyloseq, which was used to calculate diversity and abundance indices and construct the respective graphs. Linear discriminant analysis (LDA) effect size analysis (LEfSe) was used to identify the differentially abundant taxa in the BARF group versus the commercial-diet group. ResultsThe diet causes changes in fecal microbiota composition and diversity, with richness and diversity being higher in BARF-fed dogs. Beta diversity analyses confirmed that diet is directly related to microbiota composition regardless of breed or sex. Differentially enriched taxa were identified in each of the diets as Fusobacterium, Bacteroides, and Clostridium perfringens in BARF-fed dogs and Prevotella, Turicibacter, Faecalibacterium, and Peptacetobacter (Clostridium) hiranonis, mostly relevant in carbohydrate metabolism, in commercial-fed dogs. ConclusionsThis study is the first one carried out in dogs from Colombia that seeks to identify changes in the intestinal microbiota concerning natural BARF type diet and commercial diet using a metabarcoding approach. Important differences were identified in terms of richness, diversity, and differentially enriched bacteria in each of the diets. The microbiota of dogs fed the BARF diet was characterized by higher richness and diversity compared to the commercial diet. However, it was identified that BARF-fed dogs can potentially acquire more opportunistic infections by pathogens of importance such as C. perfringens. Most of the taxa enriched in commercial diet-fed dogs are linked to carbohydrate metabolism, which may be directly related to diet composition.