Dietary Cholesterol Research Articles

Specific role of NAD+ biosynthesis reduction mediated mitochondrial dysfunction in vascular endothelial injury induced by chronic intermittent hypoxia.

Cardiovascular diseases (CVD) are prevalent among those with obstructive sleep apnea (OSA) and are the leading cause of death in these individuals. However, due to clinical confounders, the mechanism by which OSA induces CVD is still unclear. Previous studies have shown that chronic intermittent hypoxia (CIH) and high cholesterol diet (HCD) induce distinct characteristics of atherosclerotic plaques, highlighting the specific mechanisms involved in CIH-induced vascular endothelial injury. This study aims to investigate whether nicotinamide adenine dinucleotide (NAD+) biosynthesis reduction-mediated mitochondrial dysfunction is responsible for vascular endothelial injury induced by CIH and to elucidate its specific role in this process. Models were established to stimulate human umbilical vein endothelial cells (HUVECs) with CIH and oxidized low-density lipoprotein (ox-LDL), and the NAD+ biosynthesis-related indicators, such as NAD+ levels and nicotinamide phosphoribosyltransferase (NAMPT) enzyme activity, were measured in this model. Additionally, interventions were performed by supplementing NAD+ levels with nicotinamide mononucleotide (NMN), inhibiting NAD+ synthesis with FK866, and evaluating mitochondrial function, oxidative stress status, vascular constriction and dilation function, and endothelial adhesion function in these models. A comparative study was conducted to assess the effects of these interventions. We found that under CIH conditions, NAMPT enzyme activity was inhibited, leading to a reduction in NAD+ biosynthesis and a decrease in NAD+/NADH ratio. At the same time, CIH caused mitochondrial dysfunction in HUVECs, including a decrease in adenosine triphosphate (ATP) content and mitochondrial membrane potential, as well as the activity of respiratory chain complex I and III, induced an increase in oxidative stress levels in endothelial cells, impaired vascular constriction and dilation function, and significantly increased expression of adhesion factors. The impact of CIH on endothelial cell-related mitochondrial function and endothelial function was restored by supplementing NMN. Although ox-LDL also causes multi-level endothelial injury, it does not involve the NAD+ pathway, as there were no significant changes in the related indicators, and the impaired endothelial function under ox-LDL conditions was not restored by supplementing NMN. CIH-induced vascular endothelial injury may be associated with NAD+ biosynthesis reduction-mediated mitochondrial dysfunction. Supplementing NAD+ precursors to increase its levels may be a potential intervention to ameliorate CIH-induced vascular endothelial injury, while it does not have a significant effect on endothelial injury caused by ox-LDL.

Dynamical modeling the effect of glucagon-like peptide on glucose–insulin regulatory system based on mice experimental observation

As an emerging global epidemic, type 2 diabetes mellitus (T2DM) represents one of the leading causes of morbidity and mortality worldwide. Existing evidences demonstrated that glucagon-like peptide-1 (GLP-1) modulate the glucose regulatory system by enhancing the β-cell function. However, the detailed process of GLP-1 in glycaemic regulator for T2DM remains to be clarified. Thus, in this study, we propose an Institute of Cancer Research (ICR) mice high fat and cholesterol dietary experimental data-driven mathematical model to investigate the secretory effect of GLP-1 on the dynamics of glucose–insulin regulatory system. Specifically, we develop a mathematical model of GLP-1 dynamics as part of the interaction model of β-cell, insulin, and glucose dynamics. The parameter estimation and data fitting are in agreement with the data in mice experiments In addition, uncertainty quantification is performed to explore the possible factors that influence the pathways leading to the pathological state. Model analyses reveal that the high fat or high cholesterol diet stimulated GLP-1 plays an important role in the dynamics of glucose, insulin and β cells in short-term. These results show that enhanced GLP-1 may mitigate the dysregulation of glucose–insulin regulatory system via promoting the β cells function and stimulating secretion of insulin, which offers an in-depth insights into the mechanistic of hyperglycemia from dynamical approach and provide the theoretical basis for GLP-1 served as a potential clinical targeted drug for treatment of T2DM.

Biochemistry and transcriptome analysis reveal condensed tannins alleviate liver injury induced by regulating cholesterol metabolism pathway

Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease (NAFLD). It remains unknown whether dietary intake of condensed tannins (CTs) have distinguishable effects to alleviate liver damage caused by a high cholesterol diet. Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks, and given CTs treatment at a dosage of 200 mg/(kg·day) at the same time. The results indicated that compared with mice fed a normal diet, a high cholesterol diet group resulted in significant weight loss, dysregulation of lipid metabolism in blood and liver, and oxidative stress in the liver, but CTs treatment dramatically reversed these negative effects. Hematoxylin and eosin (H&E) staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake. CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation. Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.

Cholesterol-rich dietary pattern during early pregnancy and genetic variations of cholesterol metabolism genes in predicting gestational diabetes mellitus: a nested case-control study

BackgroundHigher dietary cholesterol intake during pregnancy increases risk of gestational diabetes mellitus (GDM). However, no studies have investigated interindividual variability in cholesterol metabolism and the association of genetics and diet on GDM. ObjectiveTo prospectively evaluate the joint association of cholesterol-rich dietary patterns and polymorphisms of genes coding for cholesterol metabolism pathway proteins with GDM. MethodsA total of 1116 pregnant females from the Tongji Birth Cohort were enrolled. GDM was diagnosed according to a 75-g 2-h oral glucose tolerance test at 24-28 wk of gestation. Dietary data were collected by a validated food frequency questionnaire. The reduced-rank regression method was used to identify dietary patterns using dietary cholesterol as the response variable. Time-of-flight mass spectrometry was used for genotyping. The genetic risk score (GRS) for GDM was constructed with genetic variants in 28 cholesterol metabolism-related single-nucleotide polymorphisms (SNPs). Conditional logistic regression models were used to assess the odds ratio (OR) for GDM. ResultsThe cholesterol-rich dietary pattern was rich in livestock and poultry meat and eggs but lower in cereals. The multivariable-adjusted ORs for GDM were 1.24 (95% confidence interval: 1.06-1.44) per SD increment of cholesterol-rich pattern scores and 1.28 (1.09-1.49) per tertile GRS. The variants of the CYP7A1 rs3808607 G→T/rs8192871 G→A/rs7833904 A→T, as well as AGGG and TTGA haplotypes of 4 CYP7A1-spanning SNPs, were significantly associated with GDM. For the joint effect, the OR was 3.53 (1.71-7.31) in the highest categories of both dietary pattern scores and GRS compared with individuals with the lowest strata without significant interaction (P for interaction = 0.101). ConclusionsBoth a cholesterol-rich dietary pattern and genetic variants of cholesterol metabolism genes are associated with risk of GDM. Adherence to a cholesterol-rich dietary pattern during early pregnancy promotes the chance of GDM, especially in women with higher GRS. Clinical Trial RegistryThis trial was registered at http://www.chictr.org.cn (Registration number: ChiCTR1800016908). URL=https://www.chictr.org.cn/showprojEN.html?proj=28081

Comparison of western diet-induced obesity and streptozotocin mouse models: insights into energy balance, somatosensory dysfunction, and cardiac autonomic neuropathy.

Metabolic disorders such as obesity and type 2 diabetes (T2D) are increasingly prevalent worldwide, necessitating a deeper comprehension of their underlying mechanisms. However, translating findings from animal research to human patients remains challenging. This study aimed to investigate the long-term effects of Streptozotocin (STZ) on metabolic, cardiac, and somatosensory function in mice fed a Western diet (WD) of high fat, sucrose, and cholesterol with low doses of STZ administration compared to mice fed WD alone. In our research, we thoroughly characterized energy balance and glucose homeostasis, as well as allodynia and cardiac function, all of which have been previously shown to be altered by WD feeding. Notably, our findings revealed that the treatment of WD-fed mice with STZ exacerbated dysfunction in glucose homeostasis via reduced insulin secretion in addition to impaired peripheral insulin signaling. Furthermore, both WD and WD + STZ mice exhibited the same degree of cardiac autonomic neuropathy, such as reduced heart rate variability and decreased protein levels of cardiac autonomic markers. Furthermore, both groups developed the same symptoms of neuropathic pain, accompanied by elevated levels of activating transcription factor 3 (Atf3) in the dorsal root ganglia. These discoveries enhance our understanding of metabolic activity, insulin resistance, neuropathy, and cardiac dysfunction of diet-induced models of obesity and diabetes. The exacerbation of impaired insulin signaling pathways by STZ did not lead to or worsen cardiac and somatosensory dysfunction. Additionally, they offer valuable insights into suitable diet induced translational mouse models, thereby advancing the development of potential interventions for associated conditions.

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<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<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., & 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

Highland barley attenuates high fat and cholesterol diet induced hyperlipidemia in mice revealed by 16S rRNA gene sequencing and untargeted metabolomics

AimsIn this study, highland barley (HB), HB bran (HBB) and whole grain HB (WGHB) alleviating hyperlipemia and liver inflammation in high fat and cholesterol diet (HFCD) mice was investigated. MethodsAll 50 ICR mice were randomly allocated to 5 treatment groups: Normal control group, HFCD group, HB group, HBB group and WGHB group. The serum lipid profiles, liver and epididymal adipocyte histology, gut microbiota and untargeted metabolomics were adopted. Key findingsThe results suggested that HB especially HBB supplement could obviously decrease BW and BWG. Serum lipid profiles showed that HB especially HBB decreased TG, TC, LDL-C, ALT and AST levels while increased HDL-C level. Liver and epididymal adipocyte H&E staining also confirmed that hepatic injury and adipose accumulation were alleviated by HB especially HBB. Gut microbiota analysis indicated that HBB increased Bacteroidetes/Firmicutes ratio, Lactobacillus and Akkermansia muciniphila abundances while decreased Proteobacteria and Shigella abundances. Untargeted metabolomics results showed that HBB significantly increased deoxycholic acid levels compared with HFCD mice and HBB regulated arachidonic acid metabolism pathway. SignificanceThe obtained results provided important information about the processing of highland barley to retain its hypolipidemic effect and improve its acceptability and biosafety, and had a guiding effect on the development of HB products.

Total Phenolic, Flavonoid content, and Antioxidant properties of Fermented Honey-Garlic in Hyperlipidemia Rats

Hyperlipidemia and oxidative stress have been associated with disease progressions such as cardiovascular disorders, degenerative diseases, and metabolic diseases with various complications. Increasing lipid peroxidation can be detected by measuring the levels of malondialdehyde (MDA), Superoxide dismutase (SOD), and Glutathione (GSH). This study aims to analyze the total phenolic (TPC) and flavonoid content (TFC) and the effect of fermented honey-garlic (FHG) on oxidative stress parameters MDA, SOD, and GSH in hyperlipidemic rats. TPC was calculated using the Folin-Ciocalteu colorimetric method at 405nm using gallic acid as the standard. TFC was determined using a colorimetric test with AlCl3 at 433nm using quercetin as a standard. Wistar male rats were treated with a high cholesterol diet to induce hyperlipidemia (>100mg/dl), then treated with oral FHG at different doses, 2.5; 5; and 10ml/kg/day for 14 days. The positive control group was treated with simvastatin (10mg/kg/day) for 14 days orally. Serum was taken to analyse MDA, SOD, and GSH. The DPPH free radical scavenging experiment was used to calculate the antioxidant potential of the FHG at 525 nm. The results showed that FHG has a TFC value of 4.7mg QE/g and a TPC value of 6.4mg QE/g, with IC50 values of 49.34g/mL. FHG also demonstrated outstanding antioxidant capabilities indicated by significantly increase SOD levels but not MDA and GSH levels. The reduction of oxidative stress in rats treated with FGH is facilitated by antioxidant activity.

PERBANDINGAN PENGARUH PEMBERIAN JUS BUAH NAGA MERAH(HYLOCEREUS POLYRHIZUS) DENGAN OBAT SIMVASTATIN TERHADAP PENURUNAN KADAR KOLESTEROL DARAH MENCIT (MUS MUSCULUS) DENGAN KONDISI HIPERKOLESTEROLEMIA


 This study aims to determine the effect of giving red dragon fruit juice with graded doses on reducing total cholesterol levels of mice with hypercholesterolemic conditions. This research was conducted to prove the anti-cholesterol effect of red dragon fruit juice with a dose variation of 0.39 gr / 30grBB 0.65 gr / 30grBB and 0.91 gr / 30grBB in Swiss male mice with high cholesterol conditions. The subjects of this study were 30 Swiss mice which were divided randomly into 5 groups. This study was an experimental study with a pre-test and post-test control group design. Group 1 as a negative control (high cholesterol diet), group 2 as a positive control. (high cholesterol diet and simvastatin drug), and group 3 (high cholesterol diet and red dragon fruit juice 0.39 gr / 30grBB), group 4 (high cholesterol diet and red dragon fruit juice 0.65 gr / 30grBB), group 5 (high cholesterol diet and red dragon fruit juice 0.91 gr / 30grBB).The parameters measured were the total cholesterol level of mice using the easy touch GCU tool. The data of the results of the study were analyzed by one way ANOVA test with a significance level of ? = 5% with multiple comparisons (Post Hoc Test) LSD type. The results of the study with various doses showed a decrease in total cholesterol levels by 10%; 11%; 15%. The dose variation in this study gave the best results to reduce total cholesterol levels, namely at a dose of 0.91 gr / 30grBB.Based on the result of the study, shows that he administration of red dragon fruit juice showed a significant difference in total cholesterol blood levels of mice.
 Keywords : Red dragon fruit juice , Cholesterol , Antosianin , Total cholesterol

Dietary palm oil enhances Sterol regulatory element-binding protein 2-mediated cholesterol biosynthesis through inducing endoplasmic reticulum stress in muscle of large yellow croaker (Larimichthys crocea).

Sterol regulatory element-binding protein 2 (SREBP2) is considered to be a major regulator to control cholesterol homoeostasis in mammals. However, the role of SREBP2 in teleost remains poorly understand. Here, we explored the molecular characterisation of SREBP2 and identified SREBP2 as a key modulator for 3-hydroxy-3-methylglutaryl-coenzyme A reductase and 7-dehydrocholesterol reductase, which were rate-limiting enzymes of cholesterol biosynthesis. Moreover, dietary palm oil in vivo or palmitic acid (PA) treatment in vitro elevated cholesterol content through triggering SREBP2-mediated cholesterol biosynthesis in large yellow croaker. Furthermore, our results also found that PA-induced activation of SREBP2 was dependent on the stimulating of endoplasmic reticulum stress (ERS) in croaker myocytes and inhibition of ERS by 4-Phenylbutyric acid alleviated PA-induced SREBP2 activation and cholesterol biosynthesis. In summary, our findings reveal a novel insight for understanding the role of SREBP2 in the regulation of cholesterol metabolism in fish and may deepen the link between dietary fatty acid and cholesterol biosynthesis.

Cholesterol reprograms glucose and lipid metabolism to promote proliferation in colon cancer cells

Hypercholesterolemia is often correlated with obesity which is considered a risk factor for various cancers. With the growing population of hypercholesterolemic individuals, there is a need to understand the role of increased circulatory cholesterol or dietary cholesterol intake towards cancer etiology and pathology. Recently, abnormality in the blood cholesterol level of colon cancer patients has been reported. In the present study, we demonstrate that alteration in cholesterol levels (through a high-cholesterol or high-fat diet) increases the incidence of chemical carcinogen-induced colon polyp occurrence and tumor progression in mice. At the cellular level, low-density lipoprotein cholesterol (LDLc) and high-density lipoprotein cholesterol (HDLc) promote colon cancer cell proliferation by tuning the cellular glucose and lipid metabolism. Mechanistically, supplementation of LDLc or HDLc promotes cellular glucose uptake, and utilization, thereby, causing an increase in lactate production by colon cancer cells. Moreover, LDLc or HDLc upregulates aerobic glycolysis, causing an increase in total ATP production through glycolysis, and a decrease in ATP generation by OXPHOS. Interestingly, the shift in the metabolic status towards a more glycolytic phenotype upon the availability of cholesterol supports rapid cell proliferation. Additionally, an alteration in the expression of the molecules involved in cholesterol uptake along with the increase in lipid and cholesterol accumulation was observed in cells supplemented with LDLc or HDLc. These results indicate that colon cancer cells directly utilize the cholesterol associated with LDLc or HDLc. Moreover, targeting glucose metabolism through LDH inhibitor (oxamate) drastically abrogates the cellular proliferation induced by LDLc or HDLc. Collectively, we illustrate the vital role of cholesterol in regulating the cellular glucose and lipid metabolism of cancer cells and its direct effect on the colon tumorigenesis.Graphical

Association Between Dietary and Serum Cholesterol and Cognitive Function Among the U.S. Elderly from NHANES 2011-2014.

The association between dietary or serum cholesterol and cognitive performance in older adults has not been well-established. This study aimed to investigate the potential association between dietary or serum cholesterol and cognitive performance in the elderly population. A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 and 2013-2014. Diet and supplement cholesterol was estimated based on two non-consecutive 24-hour dietary recalls. Cognitive function was assessed using various statistical tests. Poor cognitive performance was defined as scores below the lowest quartile within age groups. Regression models were adjusted for demographic factors, and subgroup analyses were performed for non-Hispanic White (NHW) and non-Hispanic Black (NHB) individuals. Among 759 participants aged 60 years and above, dietary cholesterol was only associated with dietary saturated fatty acids and serum high-density lipoprotein cholesterol. There was no evidence of an association between dietary cholesterol and cognitive function, except for NHB individuals, where dietary cholesterol showed a positive correlation with cognitive function. In the overall sample and NHW participants, there were consistent positive associations between serum total cholesterol and cognitive performance across statistical tests, while such associations were rare among NHB individuals. Although not statistically significant, NHB individuals had higher dietary/supplementary/total cholesterol intake compared with NHW individuals. Within the normal range, increasing serum cholesterol may be a potential factor to prevent or relieve cognitive dysfunction. However, ethnic differences should be taken into account when considering the association between cholesterol and cognitive performance.

Deciphering conformational changes in human serum albumin induced by bile salts using spectroscopic and molecular modeling approaches

Bile salts are physiologically-important natural amphiphilic biosurfactants synthesized in the liver and play a vital role in the solubilization and digestion of dietary lipids, cholesterol, and other fat-soluble compounds in the body. Bile salts also exhibit pharmacological and biological uses as carriers for transporting scarce water-soluble drugs and other chemicals owing to their unique emulsifying, solubilizing capacities and micelle forming ability. In this context, we present an endeavor towards the possibilities underlying the interaction and binding between the most abundant plasma protein namely, human serum albumin (HSA) and bile salts to demonstrate an intriguing interplay of hydrophobic, electrostatic and hydrogen bonding effects using steady state absorption, fluorescence emission, anisotropy, time-resolved emission, and molecular modelling approaches. The outcome illuminates how amphiphilic interfaces of bile salts under various physico-chemical conditions trigger the conformational changes and binding affinities of native and molten-globule forms of HSA. To elucidate non-covalent interactions during HSA-bile salt supramolecular host–guest complex formation, changes in intrinsic (tryptophan) and extrinsic (ANS) fluorescence have been investigated. The results reveal upon binding of bile salts in subdomain IIA of HSA, the protein undergoes conformational changes mediated primarily by hydrophobic interactions. Furthermore, time-resolved fluorescence measurements provide important structural and dynamical insights into the protein-bile salt supramolecular complexes. Additionally, molecular docking studies on these complexes clearly reveal spontaneous binding of bile salts into subdomain IIA of HSA while suggesting that the binding affinity decreases with the decreasing order of hydrophobicity of the bile salts (NaDC > NaC > NaTC) (ΔGdock = −29.64 kJ mol−1, −26.15 kJ mol−1, −14.35 kJ mol−1), respectively. This study exclusively highlights the molecular mechanism of conformational perturbation in the native (pH 7) and molten-globule (pH 3) forms of HSA, induced by bile salts. We believe that the results reported herein will be helpful in the design and formulation of protein-bile salt-based pharmacological carriers suitable for drug delivery.

Corydalis saxicola Bunting total alkaloids improve NAFLD by suppressing de novo lipogenesis through the AMPK-SREBP1 axis

Ethnopharmacological relevanceAlong with the gradually increasing incidence, nonalcoholic fatty liver disease (NAFLD) has already been influencing the health of more and more people in the world. Corydalis saxicola Bunting (CSB), a valuable folk medicine, is the dried whole grass of a perennial herb, Yanhuanglian (Papaveraceae), which has significant effects on various hepatitis, liver fibrosis, cirrhosis and other liver diseases. Corydalis saxicola Bunting total alkaloids (CSBTA), a mixture of alkaloids extracted from CSB, exhibit widely-accepted hepatoprotective effects. Aim of the studyThis study aimed to explore the therapeutic potential of CSBTA on NAFLD and the underlying mechanism. Materials and methodsA mice model was established by high fat and high cholesterol diet (HFHCD) to study the benefits of CSBTA on the progression of NAFLD. The efficacy of CSBTA on NAFLD was revealed systematically via RNA-sequencing analysis. Further efficacy and molecular mechanism study were explored in mouse primary hepatocytes and HepG2 cells stimulated with high energy with or without pharmacological inhibition or gene silencing. ResultsCSBTA effectively improved the major hallmarks of NAFLD including liver lipid accumulation, liver injury, inflammation and fibrosis in HFHCD-fed mice. RNA sequencing and targeted qPCR analysis jointly evidenced CSBTA significantly suppressed the expression of Srebf1, Acc1 and Fasn which are the genes responsible for fatty acid biosynthesis. Moreover, stable isotope tracer test denoted CSBTA reduced lipid accumulation via interrupting fatty acid biosynthesis in hepatocytes or the liver. Mechanistically, CSBTA could impede SREBP1 maturation via AMPK activation, thereby reducing DNL-derived lipid accumulation in hepatocytes. ConclusionsCSBTA protected against hepatic steatosis and other hallmarks of NAFLD induced by HFHCD via suppressing DNL, through modulating the AMPK-SREBP1 axis. CSBTA may therefore have a therapeutic potential for NAFLD treatment.

Association between type 2 diabetes and different types of dietary fats: A case-control study

The effect of dietary fats on type 2 diabetes (T2D) is not clear. This study aimed to determine the association between T2D and dietary fatty acids among Iranian adults. This case-control study was performed on 4241 participants aged 35-70, including 1804 people with T2D and pre-diabetes as the case group and 2437 people without diabetes as the control group. Dietary intake was assessed using a food frequency questionnaire (FFQ). The cases had higher age (48.36±8.62 vs. 54.53±7.75y, P<0.001), weight (73.7713.41 vs. 76.18±13.49kg, P=0.001), body mass index (BMI) (28.02±4.70 vs. 24±4.74kg/m2, P=0.001), right systolic blood pressure (RSBP) (113.33±16.7 vs. 121.61±17.24mmHg, P=0.001), right diastolic blood pressure (RDBP) (71.41±10.53 vs. 75.33±9.92mmHg, P=0.001), fasting blood sugar (FBS) (96.87±19.39 vs. 169.95±69.28mg/dl, P=0.001), blood urine nitrogen (BUN) (13.65±3.74 vs. 14.26±4.03mg/dl, P=0.001), triglyceride (TG) (141.61±99.37 vs. 175.96±114.74mg/dl, P=0.001), alkaline phosphatase (ALP) (218.24±66.35 vs. 246.97±72.65 IU/L, P=0.001), low-density lipoprotein cholesterol (LDL) (111.68±33.02 vs. 101.97±36.54mg/dl, P=0.001), serum glutamic-pyruvic transaminase (SGPT) (21.88±15.15 vs. 23.55±15.96 IU/L, P=0.001), gamma-glutamyl transferase (GGT) (24.66±20.42 vs. 30.72±30.43 IU/L P=0.001), and cholesterol (192.45±39.1190 vs. 187.12±46.19mg/dl P=0.001) compared to the control group. T2D was negatively associated with dietary intake of PUFAs (OR=0.93, CI95%:0.84-1.03, P=0.01) and positively associated with dietary cholesterol (OR: 1.01, CI95%:1.001-1.01, P=0.02). In summary, cholesterol was positively and PUFAs were negatively associated with diabetes. If the results of the present study on the effect of fat intake on diabetes are proven, future dietary recommendations for people at risk of diabetes may be corrected by providing diets rich in polyunsaturated fatty acids and low in cholesterol.

Effects of Nutrition Education with Intervention Mapping on Cardiovascular Disease Risk Factors in Women with Borderline Dyslipidemia: Analysis According to Menopausal Status.

Menopause causes hormonal, physical, and psychological changes that are associated with an increase in risk of cardiovascular disease (CVD). This study examined the effects of medical nutrition therapy (MNT) on CVD risk factors in pre- and post-menopausal women with borderline dyslipidemia in Korea. In total, 76 participants were divided into the MNT and control groups. MNT was performed for 12 weeks using intervention mapping with consideration of weight, blood lipid levels, and dietary assessment results. Anthropometric and biochemical measurements and dietary intake were analyzed. The dietary energy and cholesterol intake, waist circumference (WC), blood triacylglycerol and very-low-density lipoprotein cholesterol levels, and atherogenic index (AI) of the pre-menopausal MNT group decreased significantly after the intervention. Moreover, dietary cholesterol intake, WC, waist-to-hip ratio, body fat percentage, total blood cholesterol, low-density lipoprotein to high-density lipoprotein ratio, and AI decreased significantly in the post-menopausal MNT group after the intervention. MNT for 12 weeks is effective in decreasing risk factors associated with CVD in Korean women with borderline dyslipidemia, and the effects differ between pre- and post-menopausal women.

Effect of Low Fat and Low Cholesterol Diet Intervention on LDL Subgroups in Dyslipidemic Patients: Epidemiological Observational Study

Aim: According to studies, the individual cardiovascular disease (CVD) risk is predicted and low density lipoprotein cholesterol (LDL&#x0D; cholesterol) sub-group concentration better than LDL cholesterol. High fat and cholesterol intakes are generally considered to pose a risk&#x0D; on CVD. The purpose of this study is to analogize LDL sub-group concentration pre and post a diet with LowFat and LowCholesterol&#x0D; written a prescription to dyslipidemic sicks along 3 months.&#x0D; Material and Methods: Diagnosticated dyslipidemia sicks (n=47) on the part of the endocrinologist were pursued along 3 months&#x0D; via a LowFat, LowCholesterol diet upon a lasting a month basis, on condition that they were proper for each. Before and after dietary&#x0D; intervention periods, biochemical parameters and anthropometric measurements were compared.&#x0D; Results: A sum of 47 participants (15 men and 32 women) with an average age of 48.51±9.86 years were involved. 13 women were at&#x0D; premenopausal and 19 women were at postmenopausal stages of 32 women involved. Small dense LDL (Sd-LDL) decreased from 11.0&#x0D; (0.0-37.0) mg/dL at the beginning to 7.0 (0.0-68.1) mg/dL after the dietary intervention, but this decline was unimportant (p=0.686).&#x0D; Midbands (MiDC, MidB, MidA) subgroups of intermediate density lipoprotein cholesterol (IDL-cholesterol) declined considerably after&#x0D; dietary interference (p

Metabolic programs of T cell tissue residency empower tumour immunity.

Tissue resident memoryCD8+ T (TRM) cells offer rapid and long-term protection at sites of reinfection1. Tumour-infiltrating lymphocytes with characteristics of TRM cells maintain enhanced effector functions, predict responses to immunotherapy and accompany better prognoses2,3. Thus, an improved understanding of the metabolic strategies that enable tissue residency by T cells could inform new approaches to empower immune responses in tissues and solid tumours. Here, to systematically define the basis for the metabolic reprogramming supporting TRM cell differentiation, survival and function, we leveraged in vivo functional genomics, untargeted metabolomics and transcriptomics of virus-specific memoryCD8+ T cell populations. We found that memory CD8+T cells deployed a range of adaptations to tissue residency, including reliance on non-steroidal products of the mevalonate-cholesterol pathway, such as coenzyme Q, driven by increased activity of the transcription factor SREBP2. This metabolic adaptation was most pronounced in the small intestine, where TRM cells interface with dietary cholesterol and maintain a heightened state of activation4, and was shared by functional tumour-infiltrating lymphocytes in diverse tumour types in mice and humans. Enforcing synthesis of coenzyme Q through deletion of Fdft1 or overexpression of PDSS2 promoted mitochondrial respiration, memoryT cell formation following viral infection and enhanced antitumour immunity. In sum, through a systematic exploration of TRM cell metabolism, we reveal how these programs can be leveraged to fuel memoryCD8+ T cell formation in the context of acute infections and enhance antitumour immunity.

Microbial oil, alone or paired with β-glucans, can control hypercholesterolemia in a zebrafish model

Dyslipidemia is often associated with unhealthy dietary habits, and many mammalian studies have explored the mode of action of certain bioactive compounds such as β-glucans and n-3 PUFAs to understand their potential to normalize the lipid metabolism. There are only a few investigations that adopted omic approaches to unveil their combined effect on hypercholesterolemia. Zebrafish (Danio rerio) was used as a model organism to reveal the efficacy of Schizochytrium oil and β-glucans (from Euglena gracilis and Phaeodactylum tricornutum) against cholesterol-rich diet induced dyslipidemia. One of the folowing four diets was fed to a particular group of fish: a control high-cholesterol diet, a Schizochytrium oil diet or one of the two diets containing the oil and β-glucan. The plasma HDL, expression of hepatic genes linked to, among others, ferric ion binding and plasma phosphatidylcholines were higher and plasma cholesterol esters and triacylglycerols were lower in the microbial oil-fed fish compared to the fish fed high cholesterol diet. While the fish fed a mix of microbial oil and Euglena β-glucan had lower plasma triacylglycerols and expression of hepatic genes linked to PPAR signaling pathway and enriched biosynthesis of plasma unsaturated fatty acids, the fish fed microbial oil-Phaeodactylum β-glucan combination had lower abundance of triacylglycerols rich in saturated and mono-unsaturated fatty acids and cholesterol esters in the plasma.

Balancing dietary plant-based lipids and cholesterol to increase fillet omega-3 deposition in rainbow trout (Oncorhynchus mykiss) fed a diet without animal ingredients

We hypothesized that a low phytosterol oil, such as soybean oil, in combination with an α-linolenic acid (ALA) rich oil, such as linseed oil, and supplemental cholesterol could effectively replace fish oil in salmonid feeds. As such, the primary objective was to blend soybean oil with linseed oil and supplemental cholesterol to maintain fish growth and increase de novo production of the omega-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in trout muscle, since EPA and DHA have been identified as beneficial nutrients in human nutrition, and farmed seafood must meet consumer needs and expectations. To accomplish this, we used soy oil for its low phytosterol properties in combination with linseed oil for its n-3 FA content, with and without cholesterol to improve utilization. Upon conclusion of the study, our results did not support our hypothesis. Trout fed plant-based diets containing any amount of soy oil had reduced growth performance. Only fish fed the plant-based diet with 100% linseed oil plus supplemental cholesterol grew as well as both control groups, fishmeal/fish oil and plant meal/fish oil. Dietary cholesterol supplementation increased plasma cholesterol levels and EPA in fillets (P < 0.05). Two-way ANOVA demonstrated that growth performance and muscle EPA content were significantly increased in fish fed cholesterol-supplemented diets. However, expression of genes involved in fatty acid biosynthesis were not enhanced by cholesterol, suggesting a potential disconnect between gene expression and functional activity. Although our hypothesis failed and soybean oil was found to be less accepted by the fish, resulting in lower growth and feed intake, we were successful in developing a high soy-protein diet (35%) with all-plant ingredients using linseed oil and supplemental cholesterol that resulted in equal fish performance to fish fed a fishmeal/fish oil control diet. More research is needed to identify a cost-effective EPA/DHA source to meet consumer needs and expectations for n-3 FA in trout fillets.