High Fat Research Articles

RGS5 balances macrophage vs vascular smooth muscle cell origin of foam cells in apoE-deficient plaques

Abstract Background G Protein Coupled Receptors and regulators of G-protein signalling (RGS), play a pivotal role in the signalling processes associated with atherosclerosis [1]. RGS5 is highly expressed in aortic tissue [2]. Development of atherosclerotic plaque is a complex process that involves foam cells originating from macrophages (Mϕ) and/or vascular smooth muscle cells (VSMCs). Differentiation of Mϕ and VSMC into various intermediary cells of varying inflammatory potency affects atherosclerotic plaque composition and vulnerability [3]. We hypothesize that RGS5 is involved in signalling of foam cell transition and thus, plaque biology. Purpose To evaluate the role of RGS5 on atherosclerotic plaque complexity and shifts of foam cell origin. Methods ApoE-/-RGS5+/+ and ApoE-/-RGS5-/- mice were fed a high fat Western Diet for 14 weeks. Cryosections bearing aortic valve cusps were used for staining. Lesion size was quantified on hematoxylin and eosin staining. Plaque composition was assessed by CD68, CD45, Oil red O and collagen staining. Triple staining was performed for CD45, CD68 and aSMA. Double immunofluorescent staining for CD45 and pro- and anti-inflammatory markers was carried out. Co-Localisation was analysed by Zeiss Zen. Data were analysed using Mann-Whitney-U test. Results Lesion size was significantly reduced in RGS5-deficient mice in comparison to control (in mm2: 0.398±0.02 vs 0.191±0.09, p=0.0001, n=15). Relative areas positive for Oil Red O and collagen did not differ between genotypes. Area positive for leukocyte marker CD45 increased significantly by 30.8% (p<0.0001, n=15), whereas area positive for CD68 was reduced by 10.3% (p=0.0292, n=15) in RGS5-deficient mice. Absence of RGS5 decreased co-localization of Mϕ-derived foam cells by 23% (p=0.03734, n=4-5) while leading to an 5.8% increase in aSMA-derived foam cells compared to control. Area positive for pro-inflammatory M1 Mϕ marker CD86 and iNOS increased by 36.3% and 36.8% after RGS5 knock-out (p<0.0001, n=15). No difference in M2 Mϕ positive area was observed when RGS5 was lacking. Conclusion RGS5 promotes plaque formation. The number of Mϕ-derived foam cells is increased by RGS5, while it reduces inflammatory M1 Mϕ. Interestingly, there were no differences in numbers of M2 Mϕ, indicating RGS5 inhibits VSMCs transition to M1 Mϕ resulting in an overall decrease of CD68-positive foam cells. Further study is required to determine molecular signalling of RGS5 that modulates the phenotype of Mϕ- and VSMC-derived cells. RGS5 could be useful as therapeutic target to suppress undesirable plaque phenotypes and to reduce acute cardiovascular events.

Novel method in mice to evaluate left atrial (LA) systolic contribution to left ventricular volume (LV) using pressure-volume (PV) loops

Abstract Background LA myopathy is a critically important non-LV contributor to the progression of HFpEF (heart failure with preserved ejection fraction) in patients and is associated with a severe phenotype, leading to impaired cardiac output reserve and reduced exercise capacity. In normal humans LA systole contributes ~20% of total LV filling, but with HFpEF, this contribution decreases to <16% with a greater reliance on this contribution to LV filling. Purpose We sought to investigate LA function as a critical component of cardiac function analysis by utilizing the LV pressure signal to identify and quantify the contribution of volume during LA systole to the total LV volume in mice with HFpEF. Methods Hypertension (HTN)-associated HFpEF C57BL/6J mice were subjected to chronic aldosterone infusion and 1% NaCl for 4 weeks (SAUNA model). Obesity after a high fat diet (HFD: 60% fat diet) for 16 weeks followed by the SAUNA protocol, induced HTN and obesity associated HFpEF. Blood pressure was monitored weekly. Mice were anesthetized with isoflurane, intubated, chest opened to expose the heart and allow placement of a PV catheter (Transonic) which was introduced into the LV via apical stab with a 27G needle. Calibration of the PV catheter was performed according to the manufacturer’s instructions. Atrial systole was identified using 2nd order derivative of the LV pressure signal. Contribution of LA systole was calculated using volume at the beginning of LA systole identified by the 2nd order derivative of the LV pressure signal and subtracting from the LV end diastolic volume. The % of LA systole contribution was calculated as a % of the total LV stroke volume. Data was analyzed with LabChart pro software (AD Instruments). Results SAUNA mice had normal LVEF, moderate HTN and lung congestion. PV relationships demonstrated Tau was impaired in HFpEF vs. control mice (14±1 vs. 10±0.5 ms) with a shift of the PV loop to the left (Fig. A.) In control mice, the atrial systole contributed 39± 4% to LV volume and was impaired in HFpEF mice 20± 3% a 1.95-fold reduction (P<0.01). Importantly atrial systole contribution was increased in obese mice 53±5 %. However, the combination of obesity and HTN, both common comorbidities in HFpEF, resulted in a reduced LA systole contribution by 1.43-fold to 37± 9%, (P<0.005; Fig B). Conclusion A novel method of % atrial systole from LV PV loop using 2nd order derivative to quantify the volume contribution of atrial systole to total LV stroke volume was identified in mice. LA dysfunction was present in murine HTN-associated HFpEF with/without obesity.

Moderate intensity exercise training ameliorates the heart failure with preserved ejection fraction phenotype in a preclinical model by improving cardiometabolic fitness

Abstract Introduction and Aim Exercise intolerance is a hallmark feature of patients with heart failure with preserved ejection fraction (HFpEF).While clinical evidence suggests potential benefits of exercise training in HFpEF, its mechanisms remain largely unknown.In this study, we used a translationally relevant murine model of cardiometabolic HFpEF(1) to assess whether moderate intensity continuous training(MICT) can ameliorate the HFpEF phenotype in mice and promote cardiometabolic health. Methods Twenty-five adult, male C57BL/6N were fed with the combination of high fat diet(HFD;D12492,Research diet)and L-NAME(0.5 g/L,in drinking water) for 15 weeks to elicit HFpEF as previously described(1).After the establishment of the HFpEF phenotype, mice were randomized in two groups:sedentary(SED,n= 10) and exercised(MICT,n=15)mice.MICT was carried out according to the protocol:running on 10-degree positive inclination treadmill for 8 consecutive weeks,5 times/week,60 minutes/day,at a speed gradually increasing from 0.1 to 0.2 m/sec on a weekly basis.Morphometry, echocardiography(TTE),isoproterenol-induced stress echocardiography(SE),time domain nuclear magnetic resonance, and treadmill exhaustion tests were performed at the beginning and end of MICT.Additionally, at the end of MICT blood and tissues were collected for proteomics analysis(Fig1).Non-trained male C57BL/6N mice(37w) were used as controls for the HFpEF mice. Results Before randomization, all HFpEF mice were similar in terms of phenotypic characteristics. Compared to SED mice, MICT induced a significantly decrease in body weight driven by a reduction of total fat mass with an increased in lean mass(Fig2A+B).Interestingly, MICT had no impact on skeletal muscle mass for all different muscle groups evaluated (extensor digitorum longus, soleus and tibialis anterior).Importantly, MICT led to a significant improvement in exercise capacity in HFpEF mice, as shown by increased running distance and time, surpassing even the running distance seen in non-HFpEF mice (SED:62.8±18.7,MICT:305.7±13.9,non-HFpEF mice: 129.72±15.2meters,p<0.001).Preclinical surrogate of HFpEF such as pulmonary congestion, evaluated by index lung weights, improved after aerobic training.Following MICT there was a marked improvement in diastolic dysfunction(measured by E/E’ratio) both at rest(SED:36.5±3.3,MICT:23.3±5.09,p<0.001) and after isoproterenol challenge(SED:42.6±15.1,MICT:26.09±3.75,p<0.001)(Fig2C).Moreover, the wet cardiac mass was lower in the MICT group(Fig2A), suggesting potential amelioration in cardiac hypertrophy following aerobic training. Conclusion Eight weeks of supervised MICT on treadmill improves functional status, exercise capacity, and diastolic function in a cardiometabolic HFpEF murine model.The most significant effects were seen on weight loss and fat mass reduction.Our findings suggest a beneficial impact of aerobic exercise in mitigating HFpEF by improving metabolic fitness in the preclinical HFpEF model.Fig1-Study DesignFig2-Characteristics SED vs MICT groups

PI3 kinase delta governs regulatory T-cell biology and thus confers protection against atherosclerosis progression in mice

Abstract Introduction and Purpose Atherosclerosis is a chronic inflammatory disease of arteries, critically involving innate and adaptive immune cells like macrophages as well as T and B lymphocytes. Macrophages are major drivers of disease through the ingestion of lipoproteins, foam cell formation, and secretion of inflammatory mediators. Although macrophages outnumber other leukocytes in atherosclerotic plaques, T and B cells can shape the course of disease by promoting or mitigating inflammatory responses. The phosphoinositide 3-kinase delta (PI3Kd) exerts a key role in the regulation of immune responses including activation, proliferation, differentiation, and effector function of lymphocytes. Therefore, PI3Kd may represent a promising target for the modulation of inflammatory diseases. Consequently, we aimed to analyse the role of PI3Kd during atherogenesis. Methods and Results To investigate the role of haematopoietic PI3Kd in atherosclerosis, bone marrow from PI3Kd-/- or PI3Kd+/+ mice was transplanted into Ldlr-/- mice. After a 6-weeks-challenge by high fat diet, PI3Kd-/- recipient Ldlr-/- mice displayed profoundly impaired CD4+ and CD8+ T-cell numbers, CD4+ T-cell activation, CD4+ effector T-cell differentiation, and proatherogenic CD4+ T-helper (Th) 1 responses in para-aortic lymph nodes and spleen compared with PI3Kd+/+ transplanted controls. Surprisingly, the net effect of PI3Kd deficiency was a substantial increase of aortic inflammation and atherosclerosis in Ldlr-/- mice. Whereas plaque content and functions of macrophages including foam cell formation, efferocytosis, and cytokine secretion remained largely unaffected, haematopoietic PI3Kd ablation strongly reduced mature B cells and serum immunoglobulins in Ldlr-/- mice. Importantly, PI3Kd deficiency severely impaired numbers, proliferation, immunosuppressive functions, and stability of regulatory CD4+ T cells (Tregs). Consequently, adoptive transfer of PI3Kd+/+ Tregs fully restrained the atherosclerotic plaque burden in PI3Kd-/- transplanted Ldlr-/- mice without affecting B-cell numbers and serum immunoglobulins, whereas transferred PI3Kd-/- Tregs failed to relieve atherosclerosis progression. Conclusions Here, we demonstrate that PI3Kd plays a crucial role in Tregs, Th1 cells, and B cells during atherogenesis. Lack of PI3Kd signalling specifically in atheroprotective Treg responses outplays its impact on B-cell and proatherogenic Th1 responses, thus leading to aggravated atherosclerosis. Hence, PI3Kd is a key regulator of Treg biology and thereby protects against atherosclerosis, suggesting that fine-tuning PI3Kd signalling may represent a promising target for Treg-directed therapy.

The BET inhibitor Apabetalone protects against heart failure with preserved ejection fraction by suppressing myocardial inflammation

Abstract Background Posttranslational histone modifications, play a major role in cardiac hypertrophy and dysfunction. Apabetalone (APA), a selective inhibitor of bromodomain and extraterminal containing protein family (BET) proteins, prevents bromodomain-containing protein 4 (BRD4) interactions with chromatin thus modulating transcriptional programs in different organs. Purpose We sought to investigate whether APA could be beneficial in cardiometabolic heart failure with preserved ejection fraction (cHFpEF). Methods Mice were subjected to high fat diet feeding and L-NAME treatment for 15 weeks to induce cHFpEF. Histology, mouse echocardiography (Vevo3100) and Treadmill exhaustion test were performed. Unbiased gene expression profiling by PCR array and proteomics analysis (Olink) was employed in left ventricular (LV) myocardial specimens from HFpEF mice and control animals. Cultured cardiomyocytes (CMs) treated with palmitic acid (PA) were used as an in vitro model of metabolic stress. cHFpEF mice were chronically treated with the BET inhibitor APA (150mg/kg/day) or vehicle (DMSO). In order to translate our findings to the human setting, passive stiffness of skinned CMs collected from cHFpEF patients was assessed before and after APA treatment. Results HFpEF mice displayed LV hypertrophy, diastolic dysfunction, myocardial fibrosis, lung congestion and impaired exercise tolerance as compared to controls. Interestingly, diastolic dysfunction - assessed by E/A ratio and isovolumic relaxation time (IVRT) - and lung congestion were significantly reduced in HFpEF mice treated with APA, while exercise tolerance was improved. Transcriptomic analysis in PA-treated CMs and LV mouse specimens from cHFpEF mice showed a profound deregulation of genes controlling inflammation, namely IL-6, TNF-alpha, and IL-1beta. ChIP assays showed BRD4 occupancy on the promoter of several inflammatory genes, including IL6. Treatment with APA suppressed most of inflammatory genes, with a pronounced effect on IL6 expression. Moreover, APA reduced circulating levels of several inflammatory chemokines. The beneficial effects of APA were explained by modulation of IL-6/CaMKII/STAT3 pathway both in cHFpEF hearts and PA-treated CMs. In skinned CMs from cHFpEF patients, both APA and IL6 blockade were able to attenuate passive stiffness. Conclusions Our findings set the stage for preclinical studies and exploratory clinical trials testing APA in patients with cHFpEF.

A novel VCP modulator, KUS121, attenuates atherosclerosis progression by maintaining intracellular ATP and mitigating ER stress in endothelial cells

Abstract Back ground: Endoplasmic reticulum (ER) stress signaling pathways have pivotal roles in atherosclerosis progression. Recently, we have developed Kyoto University Substance (KUS) 121, which selectively inhibits ATPase activities of valosin-containing protein (VCP) and consequently saves intracellular ATP consumption and mitigates ER stress. KUS121 are known to have protective effects on several disease models including ischemic heart disease and heart failure. However, the efficacy of KUS121 against atherosclerosis was still unclear. Purpose To elucidate the effect of KUS121 on atherosclerosis and its mechanisms. Methods and Results The daily treatment of KUS121 reduced atherosclerosis progression by approximately 40% and macrophage burden in the plaques were also significantly decreased in ApoE knockout mice on high fat diet. Interestingly, we found that C/EBP homologous protein (CHOP), an established ER stress marker, was mainly expressed in plaque endothelium. Therefore, we assessed the action of KUS 121 in endothelial cells using the EA.hy926 cell line. Consequently, it was demonstrated that KUS121 attenuated ER stress-induced apoptosis and downregulated the IRE1α-associated inflammatory pathways. Consistent with these in vitro findings, KUS121 treatment also significantly reduced endothelial apoptosis assessed by TUNEL staining and inflammation examined by immunostaining of NF-κB and ICAM1 in atherosclerotic plaques. Moreover, KUS121 treatment attenuated the recruitment of inflammatory Ly6C high monocytes assessed by bead-labeling technique, which could be due to the reduction of endothelial ICAM1 expression. Furthermore, we also demonstrated that maintenance of intracellular ATP levels mitigates ER stress and prevents pathological states in endothelial cells. Conclusion KUS121 can be a new therapeutic option for atherosclerotic diseases by maintaining intracellular ATP levels and attenuating ER stress-induced apoptosis and inflammation in plaque endothelium.

A simple action reduces high fat diet intake and obesity in mice.

Diets that are high in fat cause over-eating and weight gain in multiple species of animals, suggesting that high dietary fat is sufficient to cause obesity. However, high-fat diets are typically provided freely to animals in obesity experiments, so it remains unclear if high-fat diets would still cause obesity if they required more effort to obtain. We hypothesized that unrestricted and easy access is necessary for high-fat diet induced over-eating, and the corollary that requiring mice to perform small amounts of work to obtain high-fat diet would reduce high-fat diet intake and associated weight gain. To test this hypothesis, we developed a novel home-cage based feeding device that either provided high-fat diet freely, or after mice poked their noses into a port one time - a simple action that is easy for them to do. We tested the effect of this intervention for six weeks, with mice receiving all daily calories from high-fat diet, modifying only how they accessed it. Requiring mice to nose-poke to access high-fat diet reduced intake and nearly completely prevented the development of obesity. In follow up experiments, we observed a similar phenomenon in mice responding for low-fat grain-based pellets that do not induce obesity, suggesting a general mechanism whereby animals engage with and consume more food when it is freely available vs. when it requires a simple action to obtain. We conclude that unrestricted access to food promotes overeating, and that a simple action such as a nose-poke can reduce over-eating and weight gain in mice. This may have implications for why over-eating and obesity are common in modern food environments, which are often characterized by easy access to low-cost unhealthy foods.

Chemical Composition of Acid Soluble Collagen (ASC) Isolated from Indonesia Local “Kacang” Goat Skin (<i>Capra aegagrus hocus</i>)

Collagen from the local "Kacang” goat skin is a natural raw material in the halal food industry in Indonesia. This study aims to isolate acid-soluble collagen (ASC) from “Kacang” goat skin and characterize its chemical properties. The collagen was derived from one-year-old goat skin and cured in acid condition for 48 hours at 4°C to eliminate meats, fat, and hair. The cleaned skins were treated at 1:10 (w/v) of 0.1 M NaOH for 0, 24, and 48 h at 4°C. It was then neutralized in distilled water and extracted with 0.5 M acetic acid at a 1:10 (w/v) ratio for 24, 48, and 72 h at 4°C. The yield of ASC was 21%, characterized by chemical composition, soluble protein, differential scanning calorimeter (DSC), and protein molecular weight. The chemical composition of ASC was 11.15% (moisture), 9.04% (protein), 0.98% (fat), and 0.052% (ash). ASC has the highest collagen solubility in NaCl 5% at pH 2. ASC also has thermal stability with a low profile pattern of molecular weight. In conclusion, “Kacang” goat skin from Indonesia might be used to make a value-added product because it has a high moisture content and low fat level.

Productive, Physiological, and Environmental Implications of Reducing Crude Protein Content in Swine Diets: A Review.

Pig production is one of the most important providers of high-quality proteins and amino acids (AAs) to human nutrition. In this sector, feeding has an important economic and environmental impact. A strategy to reduce production costs and negative sustainability effects is reducing dietary crude protein (CP) contents with or without AA supplementation. This review addresses the different aspects related to this strategy, particularly the effects on growth performance and pork traits in piglets and growing and finishing pigs, as well as the physiological molecular mechanisms' underlying effects. Insight is also provided into the effects of dietary CP reduction on the productive performances of alternative pig production systems and breeding boars and sows. Finally, an overview is conducted on the effects of dietary CP reduction on ammonia, odor, and greenhouse gas emissions arising from pig production systems. Overall, CP reduction may lead to production losses, albeit they can be, to some extent, hindered by adequate AA supplementation. Losses are particularly relevant during the post-weaning phase, whereas in finishing pigs, it may bring additional benefits, such as high intramuscular fat contents in some markets or improved gut barrier function with benefits to the animals' health and welfare, as well as decreased ammonia emissions to the environment.

Visceral Obesity and a High Glasgow Prognostic Score Are Key Prognostic Factors for Metastatic Colorectal Cancer Treated with First Line Chemotherapy.

The prognostic significance of a high visceral fat area (VFA) in metastatic colorectal cancer (mCRC) remains unclear. We evaluated the prognostic impact of high-VFA on the long-term outcomes of patients with mCRC who underwent chemotherapy. Ninety patients with metastatic CRC who underwent chemotherapy were included. VFA measurement was performed by pre-treatment computed tomography using image analysis system. Overall survival (OS) and progression-free survival (PFS) rates were analyzed using the Cox proportional hazards model and Kaplan-Meier curves with the log-rank test. High-VFA was identified in 39 patients. The OS (2-year OS rates: 51.6% vs 33.3%, p=0.0023) and PFS rates (2-year PFS rates: 18.0% vs 2.7%, p=0.012) were significantly lower in the high-VFA group than in the low-VFA group. In multivariate analysis, the independent significant predictors of OS were carbohydrate antigen 19-9 (CA19-9) ≥37.0 U/mL (HR: 1.99, 95%CI [1.20-3.31], p=0.007), Glasgow prognostic score (GPS) of 1 or 2 (HR: 2.65, 95%CI [1.53-4.58], p<0.001), and high-VFA (HR: 3.09, 95%CI [1.81-5.25], p<0.001). Similarly, the independent significant predictors of PFS were CA19-9 ≥37.0 U/mL (HR: 2.02, 95%CI [1.21-3.38], p=0.007), GPS of 1 or 2 (HR: 1.87, 95%CI [1.17-2.99], p=0.008), and high-VFA (HR: 2.65, 95% CI [1.61-4.35], p<0.001). We demonstrated that pre-treatment high-VFA and high-GPS were significantly associated with worse OS and PFS rates in patients with mCRC who underwent chemotherapy.

Searching for Hub Genes of Quince–Basil Co-Administration Against Atherosclerosis Using Bioinformatics Analysis and Experimental Validation

Background: Atherosclerosis (AS) has one of the highest rates of morbidity and death globally. Cydonia oblonga Mill. (quince, COM) and Ocimum basilicum L. (basil, OB) are Uyghur medicines that are often used for anti-inflammatory, anti-tumor, and cardiovascular disease treatment. This study aimed to uncover the hub genes of the quince-basil co-administration against AS and validate them. Methods: Network pharmacology analysis and bioinformatics analysis methods were utilized to map the network and obtain four hub genes. Experiments were performed in vivo and in vitro using HUVEC and zebrafish to validate the therapeutic effect of COM-OB co-administration against AS. Finally, the hub genes were validated by Western blot. Results: Screening by network pharmacology analysis and bioinformatics analysis obtained a total of 3302 drug targets, 1963 disease targets, and 1630 DEGs. A series of bioinformatic analyses were utilized to ultimately screen four hub genes, and the stability was also verified by molecular docking and molecular dynamics. COM-OB total flavonoids co-administration significantly decreased PA-induced lipid deposition in HUVEC and reduced high cholesterol-induced fat accumulation in zebrafish. Western blot results showed that COM-OB co-administration significantly affected the expression of hub genes. Conclusions: The study identified and validated four hub genes, COL1A1, COL3A1, BGLAP, and NOX4, thus providing a rationale for the treatment of AS with COM and OB co-administration.

Milk traits characterization and association studies with DGAT1 polymorphisms in Bagnolese sheep.

The Bagnolese sheep is an authochtonous dual-purpose breed (milk and meat) reared in the Campania region, whose milk is used to produce Pecorino Bagnolese cheese. Genetic information on this sheep is extremely limited, especially regarding genes affecting productions. The aim of this study was to investigate milk production traits in Bagnolese sheep and the variability of diacylglycerol acyltransferase 1 (DGAT1) gene and its effects on milk production. Milk quantity was recorded during the morning milking, while Kjeldahl and Gerber methods were used to assess protein and fat percentage (w/v) of collected milk samples. Two PCR-RFLP protocols using BamHI and MspI endonucleases for genotyping of g.5553C>T and g.8539C>T at DGAT1 locus, respectively, were set up. Bagnolese sheep milk shows high fat and protein concentrations. Genotyping revealed a high frequency of the g.5553C and g.8539C alleles (0.56 and 0.95, respectively). The association study between the SNP g.5553C>T and milk traits showed that animals with the CT genotype had a higher percentage of fat produced per milking than those with the CC and TT genotypes (p<0.01). Similar results were found for protein yield percentage, with CT individuals being more productive than CC individuals (p<0.01). Bagnolese sheep milk parameters found are associated with high yields in the resulting dairy products. CT genotype at the SNP g.5553 of DGAT1 has shown a positive association with fat and protein milk yield percentage suggesting it could be considered a marker to improve productions of this breed. Finally, the new genotyping techniques used for this study enable a cheap and reliable characterization of two DGAT1 SNPs in sheep.

Evaluation of fenugreek (Trigonella foenum-graecum L.) powder supplementation on metabolic syndrome, oxidative stress and inflammation in high fat diet fed rats

As an anti-diabetic medicinal plant, fenugreek seed (FG) (Trigonella foenum-graecum L.) has long been utilized and has many therapeutic uses. The current investigation sought to ascertain the effects of FG powder supplementation on insulin resistance, dyslipidemia, and oxidative stress in rats given a high-fat (HF) diet. Measurements of biochemical and antioxidant indicators were made in animal blood and tissue samples, including malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), reduced glutathione (GSH), superoxide dismutase (SOD), triglycerides (TG), and catalase (CAT). Furthermore, the tissues of the kidney, heart, and liver were stained histologically. HF diet feeding in rats declined in antioxidant enzyme activities, along with a rise in MDA and other indicators of oxidative stress, which were mitigated by the supplementation of FG. Additionally, FG supplementation enhanced the expression of genes corresponding to antioxidants in the liver of rats given HF diet. FG supplements in HF diet-fed rats displayed altered gene expression in the livers that metabolized fat. Histological staining of the liver demonstrated that FG supplementation reduced necrosis and the accumulation of fat droplets in the liver of rats given HF diets. In conclusion, this finding showed that FG supplementation in HF diet fed rats reduced the plasma lipids, decreased oxidative stress and raised antioxidant enzyme activities. FG may therefore aid in reducing the chronic complications linked to the HF diet in experimental rats.

Effects of Dietary Energy Profiles on Energy Metabolic Partition and Excreta in Songliao Black Pigs Under Different Ambient Temperature.

In order to further reveal the special characteristics of energy metabolism and the characteristics of energy requirements of fattening pigs grown in low-temperature environments, this study used a 2 × 2 × 2 factorial array of treatments, which harnessed two temperatures (low-temperature, LT group: 10 °C; normal-temperature, NT group: 20 °C), two feed energy levels (normal-energy, NE group: 14.02 MJ/kg metabolic energy; high-energy, HE group: 15.14 MJ/kg metabolic energy), and two feed energy sources (LF group: low fat, HF group: high fat). Thirty-two Songliao black fattening pigs with an initial body weight of 85.48 ± 2.31 kg were completely randomized into eight treatment groups, with four replicates in each treatment group and one pig in each replicate. The pigs were placed in a respiratory metabolic chamber for a 6-day trial. There was one pig per respiratory metabolic chamber in a single cage. The results showed that the average daily weight gain in the normal-temperature, high-energy, and high-fat groups was higher than that of the low-temperature, normal-energy, and low-fat groups (p < 0.05). The fat deposition rate, protein oxidation, and fat oxidation of the high-fat group were higher than those of the low-fat group (p < 0.05). The energy digestibility, protein digestibility, and fat digestibility in the high-fat group were higher than those in the normal-energy group (p < 0.05). The fat digestibility and energy deposition rate in the high-fat group were higher than those in the low-fat group (p < 0.05). The respiratory quotient in the high-energy group was lower than that in the normal-energy group (p < 0.05), and the respiratory quotient in the high-fat group was lower than that in the low-fat group (p < 0.05). There was an interaction between temperature and energy sources in terms of the respiratory quotient, fat oxidation, blood urea nitrogen content, and glucose content (p < 0.05). Appropriately increasing the energy level of the diet and improving the energy structure of the feed (increasing the level of fats and oils) will benefit Songliao black fattening pigs by increasing their energy use efficiency and at the same time reducing greenhouse gas CO2 emissions, and these changes are more pronounced in cold environments.

National school food standards in England: a cross-sectional study to explore compliance in secondary schools and impact on pupil nutritional intake.

Many countries have introduced school food standards to improve the dietary intakes of school-aged children. England has school food standards (SFS) legislation in place but little is known about how well secondary schools comply with this. We aimed to assess compliance with the SFS legislation in English secondary schools and explore the impact of the SFS on pupils' nutritional intake. We conducted a cross-sectional study with English secondary schools from 2019 to 2022. We compared SFS compliance and pupil nutritional intake in schools mandated or not mandated to comply with the SFS legislation, and explored the association between school compliance and pupil nutritional intake. We assessed the percentage of SFS (%SFS) complied with by reviewing school food menus and observing food served in school canteens. We assessed pupil nutritional intake using a 24-hour dietary recall measure (Intake24) and estimated intakes of free sugar (primary outcome) and other nutrients/foods. We used adjusted multilevel models to compare pupil intakes in the SFS-mandated and SFS-non-mandated schools, and to explore the association between school SFS compliance and pupil intakes. 36 schools (23 not mandated and 13 mandated to comply with the SFS) and 2,273 pupils participated. The median %SFS complied with was 63.9% (interquartile range 60.0-70.0%). This was similar for SFS-non-mandated (64.5%) and SFS-mandated schools (63.3%). Compliance was highest for standards applying to lunchtime (median = 81.3%) and lowest for those applying across the whole school day (median = 41.7%). It was also lower for standards restricting high fat, sugar and energy-dense items (median = 26.1%) than for standards aiming to increase dietary variety (median = 92.3%). Pupils from SFS-mandated schools had a lower mean lunchtime intake of free sugar (g) (adjusted mean difference: -2.78g; 95% CI: -4.66g to -0.90g). There were few significant associations between %SFS complied with and pupil nutritional intake. English secondary schools do not fully comply with SFS legislation regardless of whether they are mandated to comply. Schools and caterers may require monitoring and support to fully comply. There is little evidence that SFS compliance is associated with better pupil nutritional intake. Food environments outside of school also need to be considered. ISRCTN68757496 (17-10-2019).

Orange peel ethanolic extract and physical exercise prevent testicular toxicity in streptozocin and high fat diet-induced type 2 diabetes rats via Nrf2/NF-kB signaling: In silico and in vivo studies

BackgroundType 2 diabetes mellitus (T2DM) is a significant health issue affecting the quality of life including male reproductive functions. Orange peel ethanolic extract (OPEE) has been established to have antioxidant properties and has been shown to alleviate diabetic complications. This study determined to establish OPEE effect and physical exercise (EX) in T2DM-induced testicular dysfunction. Materials and methodsThirty male Wistar rats were randomly distributed in five groups as follows: control group (received 1 ml/b.w of normal saline), and groups 2–5 were induced with diabetes, with group 2 left untreated, group 3 received 600 mg/kg b.w OPEE, group 4 was subjected to EX while group 5 was treated with OPEE alongside EX. ResultsOPEE + EX ameliorated T2DM-induced decrease in sperm motility, count, and morphology and increased testicular lactate dehydrogenase, alkaline phosphate, gamma-glutamyl transferase, and lactate. T2DM-induced disruption of gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone and, testosterone was also mitigated by OPEE + EX. In addition, OPEE + EX blunted T2DM-induced increase in oxidative stress, inflammatory, and apoptotic markers and the accompanied decrease in testicular nuclear factor erythroid 2–related factor 2 (Nrf2) and increase in nuclear factor kappa B (NF-κB). Also, OPEE + EX reversed T2DM-induced testicular histology distortion. ConclusionsThe outcome of this study revealed that the combination of OPEE and EX ameliorated T2DM-mediated testicular damage via Nrf2/NF-κB signaling.

Neuroprotective Roles of Lauric Acid and Resveratrol: Shared Benefits in Neuroinflammation and Anxiety, Distinct Effects on Memory Enhancement

ABSTRACTNeuroinflammation can be triggered by a high‐fat/high‐fructose diet (HFFD), and CD36 may be an underlying mechanism. Lauric acid (LA), the major fatty acid in coconut oil, and resveratrol, the plant‐based polyphenolic compound, may exert anti‐inflammatory effects. Therefore, this study investigated the possible effects of LA and resveratrol on diet‐induced neuroinflammation and CD36. Healthy male C57BL/6 mice (8 weeks of age, n = 31) were fed a control diet (10%kcal fat) or diets containing high fat (60%kcal fat) and fructose (5% w/v fructose drinking water) for 6 weeks, ad libitum. Supplemented to the HFFD, mice daily received resveratrol (7.5 mg/kg) (HFFD‐RSV) or LA (750 mg/kg) (HFFD‐LA). At the end of the study, HFFD resulted in anxiety‐like behavior, reduced locomotor activity, neuroinflammation (increased brain GFAP, IL‐6, MCP‐1, IFN‐γ, TNF‐α), and systemic inflammation (increased plasma GFAP, IFN‐γ, TNF‐α, IL‐12p70, reduced plasma IL‐10). HFFD‐RSV and HFFD‐LA alleviated HFFD‐induced anxiety‐like behavior, neuroinflammation, and systemic inflammation. HFFD‐LA improved memory. Brain and plasma CD36 levels were increased by HFFD and reduced by HFFD‐RSV or HFFD‐LA. Dietary resveratrol and LA intake may alleviate HFFD‐induced neuroinflammation, systemic inflammation, and anxiety‐like behavior and improve memory, as CD36 may be an underlying mechanism.

Dynamic Hydration and Viscosity Control of Konjac Glucomannan Enhance Long-Term Antiobesity Effects by Reducing Food Intake in High-Fat-Diet-Fed Mice.

The purpose of this study was to investigate the necessity and importance of dynamic hydration rate and ultimate viscosity control of konjac glucomannan (KGM) for long-term antiobesity effects in C57BL/6J mice on high-fat (HF) diets. KGM supplementation effectively attenuated HF-diet-induced increases in body and tissue weights. The hydration rate and viscosity changes of KGM in the digestive tract were found to have marked impacts on antiobesity effects. KGM with medium hydration and viscosity slowed gastric emptying and intestinal transit, leading to prolonged presence in the lower ileum, increased satiety-related hormones (GLP-1 and PYY), and an 18.27% reduction in daily food intake over 10 weeks (p < 0.05). This resulted in the greatest reduction in weight gain among HF-fed mice. In contrast, KGM with faster hydration and higher viscosity provided only short-term satiety due to rapid dilution. Furthermore, KGM improved metabolic health and altered glycolipid metabolism gene transcription while enriching beneficial gut bacteria; however, no significant differences were observed among the KGM groups in these effects. These findings highlight that synchronizing KGM's hydration rate and viscosity with digestive processes is crucial for regulating satiety and achieving long-term weight loss.

Association of STAT1 gene with milk fat and protein yield in Holstein Friesian crossbred cattle maintained in the sub-tropical climate of India.

Signal transducers and activators of transcription (STAT) genes are involved in signal mediation of various hormones and cytokines. STAT1 located on chromosome number 2 is involved in mammary gland development and is associated with milk composition traits in bovines. This study aimed to find any relationship and impact of STAT1/BspHI gene with milk fat and protein yields in a herd of Holstein Friesian (HF) crossbred cattle of sub-tropical climate of Northern India. Milk composition data of 535 adult HF crossbred cows for a period of 12 years was collected from the records maintained at Livestock Farm, Guru Angad Dev Veterinary and Animal Sciences University. First lactation data of 222 animals was chosen for further analysis. After data correction for non-genetic factors (season of calving, period of calving, interaction effect of season and period of calving and age at first calving) these animals were categorised into two groups based on corrected high and low milk fat and protein yields. Forty animals were then selected for blood collection and further laboratory analysis. Amplified using PCR-RFLP technique, the 314 bp STAT1 gene was digested using BspHI restriction enzyme. C-T polymorphism at nucleotide position 201 and 260 of the STAT1 amplicon was observed. At 201, for genotype AA and Aa, the genotypic frequencies were 0.80 and 0.20%. At 260, for genotype BB and Bb, the genotypic frequencies were 0.25 and 0.75%. Least square analysis showed a significant association of all genotypes with milk fat and protein yields. Hence, STAT1 can be used as a potential candidate gene to aid in better animal selection in breeding programmes.

Healthiness of Meat-Based Products in Comparison to Their Plant-Based Alternatives in the UK Market: A Packaging Evaluation.

This study evaluated the healthiness of meat products (n = 62) and their plant-based (PB) counterparts (n = 62) available in the UK market. Back-of-pack (BoP) and front-of-pack (FoP) nutrition label information, nutrition and health claims, and nutrient profiling model scores were compared. BoP labels revealed that meat products had higher protein, fat, and saturated fat content (p = 0.029), whilst PB alternatives were higher in dietary fibre and carbohydrates (p < 0.001). Red colour coding (FoP) for fat and saturated fat ('high') was more prominent in meat products (23 and 35%, respectively), and the red meat category had the most products with high fat and saturated fat content. Only 15% of meat products made nutrition claims compared to 40% of PB alternatives, and none included health claims. Most red meat PB alternatives made a nutrition claim, all related to the protein content (34%). The nutrient profiling model indicated that 74% of the PB alternatives were 'healthy' compared to 60% of the meat products. No association was found between the product type (meat/PB) and healthiness, except for the red meat products, which showed a significant negative association (p = 0.005), suggesting that these products corresponded to less healthy options. Therefore, PB alternatives can be considered as healthier substitutes for meat products.