Plasma TG Research Articles

6-OR: PAR2 Downregulates Adipose LPL through MIF—A Novel Adipose Mechanism Contributing to the Development of Hypertriglyceridemia

Lipoprotein lipase (LPL) is a key enzyme that hydrolyzes circulating triglycerides to release fatty acid (FA). In adipose tissue, LPL is required for lipid storage. However, it is currently unknown whether alteration of LPL in white adipose tissue (WAT) contributes to the development of hypertriglyceridemia. Our present study indicated that WAT isolated from human obese patients have increased expression of PAR2 which is negatively associated with LPL gene. The reduced LPL expression is also negatively correlated with increased plasma TG levels, suggesting that adipose PAR2 may modulate hyperlipidemia through downregulating LPL. In mice, aging and high palmitic oil diet significantly increased PAR2 expression in adipose tissue which was associated with high plasma MIF levels. PAR2 deficiency attenuates the rise of MIF, suggesting a key role of PAR2 in regulating adipose MIF release. MIF reduced LPL expression and activity in adipocytes. In a MIF overexpressed animal model (Mif lung Tg), high circulating MIF levels inhibited adipose LPL which was associated with increased plasma triglyceride but not fatty acid. Following high palmitic oil diet feeding, adipose LPL expression and activity were also reduced, and this reduction was reversed in PAR2 knockout mice. Interestingly, PAR2 mediated LPL in adipose tissue regulates hypertriglyceridemia through controlling adipocyte lipid storage. In Par2-/- mice, recombinant MIF perfusion recovered high plasma MIF levels, which decreased LPL and attenuated adipocyte lipid storage leading to hypertriglyceridemia. These data together suggest that the downregulation of adipose LPL by PAR2/MIF is an important mechanism for the development of hypertriglyceridemia. Disclosure Y.Huang: None. L.Li: None. L.Chen: None. X.Chen: None. P.Gao: None. Y.Qi: None. D.Qi: None. Funding Canadian Institutes of Health Research (PJT156116)

1654-P: Hepatic FGF21 Is Required for Curcumin and Resveratrol to Exert Their Metabolic Beneficial Effect in Male Mice

Intensive investigations have shown the profound metabolic beneficial effect of dietary intervention with plant polyphenols including curcumin and resveratrol. Recent studies have also shown that hepatic FGF21 is among the targets of dietary polyphenol intervention as well as intermittent fasting or nutritional restriction. Here we assessed whether hepatic FGF21 is required for dietary polyphenol intervention on metabolic homeostasis in mice on high fat high fructose diet (HFHF) challenge. Liver specific FGF21 null mice (Lfgf21-/-) were generated by mating Alb-Cre mice with Fgf21fl/fl mice. No appreciable defect on glucose disposal was observed in male or female Lfgf21-/- mice when they were fed with regular chow diet. In chow diet fed male but not female Lfgf21-/- mice, fat tolerance was impaired, associated with elevated fasting plasma TG level and reduced hepatic expression of Ehhadh and Ppargc1 (two downstream targets of FGF21). Following HFHF challenge, the control Fgf21fl/fl male mice exhibited response to 12-week curcumin intervention on reducing body weight, serum and hepatic TG elevation, and on improving fat tolerance. Those beneficial effects were absent in male Lfgf21-/- mice. In high fat diet challenged wild type mice, concomitant resveratrol intervention exhibited anticipated metabolic beneficial effect, associated with increased hepatic FGF21 mRNA and protein expression. Importantly, the metabolic beneficial effects of resveratrol intervention were observed in HFHF challenged Fgf21fl/fl mice but not in Lfgf21-/- mice. In wild type or transgenic female mice, we did not see appreciable beneficial effect with resveratrol intervention. Together we introduced a transgenic mouse model into the investigation of metabolic function of dietary intervention. We conclude that hepatic FGF21 is required for curcumin or resveratrol to exert its beneficial effect in male mice. Disclosure W.Shao: None. J.Feng: None. T.Jin: None. Funding Canadian Institutes of Health Research

Diets Enriched in Sugar, Refined, or Whole Grain Differentially Influence Plasma Cholesterol Concentrations and Cholesterol Metabolism Pathways with Concurrent Changes in Bile Acid Profile and Gut Microbiota Composition in ApoE-/- Mice.

This study aimed to compare the effects of diets enriched in sugar, refined grain (RG), or whole grain (WG) on circulating cholesterol concentrations and established and emerging mechanisms regulating cholesterol metabolism. Forty-four male ApoE-/- mice aged 8 weeks were randomly fed an isocaloric sugar-, RG-, or WG-enriched diet for 12 weeks. Compared to WG-enriched diet, fasting plasma LDL-C and HDL-C concentrations were higher and the mRNA expression of intestinal LXR-α was lower in sugar- and RG-enriched diets; plasma TC, non-HDL-C, TG and VLDL-C concentrations, and cecal concentrations of lithocholic acid were higher and the mRNA expression of intestinal ABCG5 was lower in sugar-enriched diet, and the mRNA expression of hepatic IDOL and cecal concentrations of lithocholic and deoxycholic acids was higher in RG-enriched diet. The relative abundance of Akkermansia, Clostridia_UCG-014, Alistipes, and Alloprevotella, which were lower in sugar- and/or RG- than in WG-enriched diet, had inverse correlations with fasting plasma cholesterol concentrations or cecal concentrations of secondary bile acids and positive correlations with gene expressions in intestinal cholesterol efflux. Conversely, the relative abundance of Lactobacillus, Lachnoclostridium, Lachnospiraceae_NK4A136_group, Colidextribacter, and Helicobacter had reverse correlations. Both sugar- and RG-enriched diets had unfavorable effects on cholesterol concentrations; yet, their effects on the gene expressions of cholesterol efflux, uptake, bile acid synthesis, and bile acid concentrations were distinctive and could be partially attributable to the concurrent changes in gut microbiota.

Effects of NUCB2/nesfatin-1 on lipid metabolism in the hepatopancreas of largemouth bass (Micropterus salmoides)

Although nucleobindin-2 (NUCB2)/nesfatin-1 has multiple biological functions, there is a scarcity of information regarding the regulatory effect of NUCB2/nesfatin-1 on lipid metabolism in mammals and fish. In order to investigate the mechanism underlying the effect of nesfatin-1 on lipid metabolism in largemouth bass (Micropterus salmoides), the sequence of NUCB2 was cloned and nesfatin-1 was expressed in prokaryotic system. Intraperitoneal injection of 5, 50 or 500 ng/g nesfatin-1 protein to determine differentially expressed genes (DEGs) in largemouth bass by transcriptomic profiling. The triglyceride and total cholesterol levels in the hepatopancreas and plasma were subsequently determined. The results showed that the NUCB2 cDNA sequence was 2015 bp in length and analyzed that NUCB2 mRNA was abundantly expressed in the hepatopancreas. RNA-seq analysis revealed that 385, 1647, and 750 genes were differentially expressed in the three groups, respectively, of which 33, 69, and 61 DEGs, respectively, were involved in lipid metabolism. GO and KEGG analysis showed that the DEGs were enriched in 24 signaling pathways related to lipid metabolism. The PPAR signaling pathway was significantly enriched following treatment with nesfatin-1. The fatty acid transport genes (ACSL, FABP3, FATP, ACBP) were significantly downregulated in the pathway (p < 0.05). Additionally, the TG (p < 0.01) and T-CHO (p < 0.05) levels in the hepatopancreas were significantly down-regulated at 50 ng/g nesfatin-1 protein injection dose, while TG and T-CHO levels in plasma were not significantly altered (p > 0.05). The present study demonstrated that at an optimal concentration, nesfatin-1 affected lipid metabolism in the hepatopancreas of largemouth bass primarily via the PPAR signaling pathway, to down-regulate the expression of fatty acid transport genes, which in turn decreased lipid synthesis in the hepatopancreas. The findings provide useful insights for further analysis of the mechanism underlying the effect of nesfatin-1, and for elucidating the regulation of lipid metabolism homeostasis in the aquaculture production of largemouth bass.

Abstract 118: Positive Adipose Liver Crosstalk Protects Adipose MTP Knockout Mice from Hepatic Steatosis on an Obesogenic Diet

Introduction: Our previous study demonstrated that adipocyte MTP regulates intracellular lipolysis by inhibiting ATGL activity. Adipose-specific MTP knockout mice (A- Mttp -/- ) had smaller adipocytes and showed increased thermogenesis and gained less weight on an obesogenic diet. They also exhibited moderately high plasma triglyceride levels and less hepatic steatosis compared to wild-type counterparts. In this study, we have elucidated the mechanism behind less hepatic lipid accumulation and moderately high plasma TG in A- Mttp -/- mice. Methods: We characterized lipoproteins and studied hepatic ApoB production. We have analyzed adipose-liver crosstalk using two strategies 1) lipidomics of adipose tissue, plasma, and liver. 2) adipokine profiling. Further, we have used western blotting and qRT-PCR to check signaling and gene expression. Results: Plasma lipid profiling revealed increased TG content in the VLDL and LDL fraction of A- Mttp -/- mice compared to Mttp f/f mice. Additionally, A- Mttp -/- mice showed significantly increased hepatic triglyceride production compared to the wild type. Lipidomic analysis revealed the movement of fatty acids from adipose tissue to the liver, resulting in significantly higher amounts of oleate, palmitate, linoleate, and stearate in the liver of A- Mttp -/- mice compared to Mttp f/f mice. A- Mttp -/- mice liver also showed significantly increased expression of genes involved in fatty acid uptake and utilization such as Cd36 , Mcad , Fatp2 , and Cpt1a compared to Mttp f/f mice. Further adipokine profiling showed a significantly higher amount of adiponectin and decreased amount of proinflammatory cytokines such as leptin in the plasma of A- Mttp -/- mice compared to Mttp f/f mice. We also found decreased ceramide levels and significantly increased phosphorylation of AMPK in the liver of A- Mttp -/- mice compared to Mttp f/f mice. Conclusion: We conclude that increased availability of substrate for TG production might contribute to increased ApoB secretion by the liver of A- Mttp -/- mice. In addition, positive cytokine profile and increased adiponectin signaling in the liver of A- Mttp -/- mice protects it from hepatic steatosis.

MLX plays a key role in lipid and glucose metabolism in humans: Evidence from in vitro and in vivo studies

Background and aimEnhanced hepatic de novo lipogenesis (DNL) has been proposed as an underlying mechanism for the development of NAFLD and insulin resistance. Max-like protein factor X (MLX) acts as a heterodimer binding partner for glucose sensing transcription factors and inhibition of MLX or downstream targets has been shown to alleviate intrahepatic triglyceride (IHTG) accumulation in mice. However, its effect on insulin sensitivity remains unclear. As human data is lacking, the aim of the present work was to investigate the role of MLX in regulating lipid and glucose metabolism in primary human hepatocytes (PHH) and in healthy participants with and without MLX polymorphisms. MethodsPHH were transfected with non-targeting or MLX siRNA to assess the effect of MLX knockdown on lipid and glucose metabolism, insulin signalling and the hepatocellular transcriptome. A targeted association analysis on imputed genotype data for MLX on healthy individuals was undertaken to assess associations between specific MLX SNPs (rs665268, rs632758 and rs1474040), plasma biochemistry, IHTG content, DNL and gluconeogenesis. ResultsMLX knockdown in PHH altered lipid metabolism (decreased DNL (p < 0.05), increased fatty acid oxidation and ketogenesis (p < 0.05), and reduced lipid accumulation (p < 0.001)). Additionally, MLX knockdown increased glycolysis, lactate secretion and glucose production (p < 0.001) and insulin-stimulated pAKT levels (p < 0.01) as assessed by transcriptomic, steady-state and dynamic measurements. Consistent with the in vitro data, individuals with the rs1474040-A and rs632758-C variants had lower fasting plasma insulin (p < 0.05 and p < 0.01, respectively) and TG (p < 0.05 and p < 0.01, respectively). Although there was no difference in IHTG or gluconeogenesis, individuals with rs632758 SNP had notably lower hepatic DNL (p < 0.01). ConclusionWe have demonstrated using human in vitro and in vivo models that MLX inhibition favored lipid catabolism over anabolism and increased glucose production, despite increased glycolysis and phosphorylation of Akt, suggesting a metabolic mechanism that involves futile cycling.

Correlation study on the relationship between dyslipidemia and carotid intima-media thickness in patients with diabetes mellitus.

To investigate the correlation between dyslipidemia and carotid intima-media thickness (IMT) in patients with diabetes mellitus. A descriptive research design was adopted in this study. One hundred and twenty patients with Type-2 diabetes mellitus who were admitted to the physical examination center of The Fourth Hospital of Hebei Medical University from June 2020 to June 2021 for physical examination were recruited to the experimental group. The 120 patients were divided into three groups according to carotid IMT: normal group, thickened group, and plaque group. Forty healthy people who underwent a physical examination during the same period were recruited as the control group. The differences in IMT in various parts of the experimental group and the control group and the differences in blood lipid indexes were compared and analyzed. In addition, the correlation between mean IMT of bilateral common carotid arteries and blood lipid levels in normal, thickened and plaque groups was compared and analyzed. The intima-media thicknesses of the internal carotid artery and bilateral common carotid arteries of the patients in the experimental group were significantly thicker than those in the healthy control group, the levels of TC, TG and LDL were higher than those in the control group, while the level of HDL was lower than that in the control group, with a statistically significant difference (p=0.00). The levels of fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), TG, TC and LDL were positively correlated with the mean IMT of bilateral common carotid arteries (p<0.05), while the level of HDL was negatively correlated with the mean IMT of bilateral common carotid arteries (p<0.05). Dyslipidemia and glucose metabolism in patients with Type-2 diabetes mellitus have a close bearing on carotid IMT. Clinically, patients with Type-2 diabetes mellitus can be judged by monitoring carotid IMT for dyslipidemia, atherosclerosis and other related complications.

Overexpression of hepatic pescadillo 1 in obesity induces lipid dysregulation by inhibiting autophagy

Previous studies indicated that increased hepatic pescadillo 1 (PES1) in type II diabetic mice was associated with lipid dysregulation. However, the role of PES1 in obesity-associated lipid dysregulation is still unknown. This study investigates the effects and underlying mechanism. Livers from obese and healthy humans and mice were collected, and C57BL/6J mice were either fed on standard diet or high fat diet (HFD). McArdle 7777 rat hepatoma cells were treated with phosphate-buffered saline and oleic acid (OA)+ palmitic acid (PA), respectively. In vitro Pes1 knockdown or overexpression and in vivo Pes1 knockdown or liver-specific ablation or supplementation of Pes1 were used to explore the modulating role of PES1. We found that obesity in humans enhanced hepatic PES1 protein, accompanied by increased plasma TG. These data are consistent with those from OA+PA-treated cells and from HFD- or Pes1 overexpression-treated C57BL/6J mice. In vitro and in vivo Pes1 knockdown in cultured cells and in ob/ob mice promoted the expression of autophagy markers (TFEB, Beclin1 and LC3B-Ⅱ) while decreasing p62 and TG, contrary to Pes1 overexpression in cells and in normal mice. Moreover, liver-specific knockout of Pes1 protected the mice fed on HFD from increased TG levels, facilitating the TFEB, Beclin1 and LC3B-Ⅱ and curbing p62. Mechanistically, OA+PA increased C/EBPβ binding to the Pes1 promoter, leading to the elevation of PES1, and subsequently enhancing PES1-facilitated ubiquitination of TFEB. Our findings reveal that overexpression of hepatic PES1 in obesity may induce TG dysregulation by inhibiting autophagy.

Evaluation of Different Copper Sources in Nile Tilapia Diets: Growth, Body Indices, Hematological Assay, Plasma Metabolites, Immune, Anti-Oxidative Ability, and Intestinal Morphometric Measurements

The goal of the current study was to compare how well Nile tilapia, Oreochromis niloticus, utilized copper (Cu) as bulk and nano sources by evaluating fish growth, body indices, hematological assays, plasma metabolites, immune and anti-oxidative abilities, and intestinal morphometric measurements. The basal diet served as a control, with no Cu added, whereas the experimental diets were formed by adding bulk-Cu and nano-Cu to the basal diet to keep Cu levels at 3 and 6 mg kg−1, respectively, in both Cu sources. Tilapia (9.10 ± 0.014 g) were fed the control diet and four experimental diets for 12 weeks. Results indicated that growth, feed utilization, and body indices demonstrated a substantial improvement (P ≤ 0.05) in tilapia that received a diet containing 3 and 6 Nano-Cu mg kg−1 diet, compared to the performance of fish that received diets containing 3 and 6 Bulk-Cu mg kg−1 diet and the control diet. Villi height, villi width, absorption area of villous (AAV), and mucosal to serosal amplification ratio (MSR) values demonstrated a substantial increase (P ≤ 0.05) in tilapia fed 3 and 6 mg kg−1 Nano-Cu compared to the values observed in fish fed the control and Bulk-Cu supplemented diets. Fish fed Bulk-Cu recorded the highest (P ≤ 0.05) hemoglobin concentration in those fed 6 mg kg−1 compared to 3 mg kg−1. Hematocrit value considerably improved (P ≤ 0.05) by supplementation of Cu, whereas the highest significant value demonstrated in fish provided 6 mg/kg−1 Nano-Cu. A fish-fed diet containing 3 mg kg−1 Nano-Cu revealed the best (P ≤ 0.05) values of plasma albumin, total protein, and globulins. Plasma HDL-C highest concentrations (P ≤ 0.05) were reported in fish fed diet supplemented with 6 mg/kg−1 either Bulk or Nano Cu, whereas values of plasma TG and VLDL-C declined as Cu supplementation level increased either from Bulk or Nano source. Also, the best (P ≤ 0.05) values of CAT and GPX were seen in fish given diet supplemented with 6 Nano-Cu mg/kg−1. Fillets of fish-fed Nano-Cu-supplemented diets showed a marked decline (P ≤ 0.05) in moisture and fat contents, while crude protein, ash, and Cu contents considerably increased in the fillet by dietary supplementation of Nano-Cu at both levels 3 and 6 mg kg−1. In conclusion, the supplemental diets with 3 or 6 Nano-Cu mg/kg−1 enhanced growth, feed utilization, body indices, fillet nutrient composition, hematological assay, plasma metabolites, immune, antioxidant activities, and intestinal morphometry of Nile tilapia.

Interdependence of glycemic and lipid modulation in cured chronic hepatitis C patients by direct-acting antiviral agents.

Chronic hepatitis C virus (HCV) infection causes various liver diseases and metabolic disorders. With direct-acting antiviral agents (DAAs), which effectively eradicate pan-genotypic HCV, hepatic and concomitant metabolic restorations are achieved. The study aims to evaluate the posttherapeutic benefits of lipid and glycemic homeostasis. Nighty-five chronic hepatitis C patients who achieved sustained virological response (SVR) by using DAAs were enrolled to collect plasma samples and fractionated lipoproteins at baseline, SVR, and during the post-SVR follow-ups for 6 months (pS6m) and 1 year (pS1yr). The lipid and glycemic parameters were analyzed to establish muturally modulatory relationships. Plasma cholesterol (Chol) and glucose were elevated at SVR from baseline, whereas plasma Chol remained increased until pS1yr; however, glucose returned to the basal level. The post-SVR responses included a peak elevation of glycated hemoglobin at pS6m, a sustained elevation of triglyceride (Tg), and sustained declines in insulin, homeostasis model assessment (HOMA)-insulin resistance, and HOMA-beta levels until pS1yr. The changes in plasma Chol and high-density-lipoprotein Chol showed positive correlations, as did the plasma Tg with low-density-lipoprotein Tg and very-low-density-lipoprotein Tg per particle load. Very-low-density-lipoprotein was found to be loaded with increased Tg and Chol and underwent efficient Tg catabolism in the form of conversion into low-density-lipoprotein. Additionally, the posttherapeutic dynamics exhibited correlations of high-density-lipoprotein Chol with plasma glucose and HOMA-beta. Irrespective of the baseline metabolic status, the posttherapeutic interdependent modulation of blood glycemic and lipid metabolic parameters were revealed in chronic hepatitis C patients following clearance of HCV viremia by DAA treatment.

Physcion prevents high-fat diet-induced endothelial dysfunction by inhibiting oxidative stress and endoplasmic reticulum stress pathways

High-fat diet (HFD)-induced obesity leads endothelial dysfunction and contributes to cardiovascular diseases. Palmitic acid (PA), a free fatty acid, is the main component of dietary saturated fat. Physcion, a chemical ingredient from Rhubarb, has been shown anti-hypertensive, anti-bacteria, and anti-tumor properties. However, the effects of physcion on endothelial dysfunction under HFD-induced obesity have not been reported. The purpose of the present study was to define the protective effect of physcion on HFD-induced endothelial dysfunction and its mechanisms involved. Obesity rat model was induced by HFD for 12 weeks. A rat thoracic aortic ring model was used to investigate the effects of physcion on HFD-induced impairment of vasorelaxation. Endothelial cell injury model was constructed in human umbilical vein endothelial cells (HUVECs) by treating with PA (0.25 mM) for 24 h. The results revealed that physcion reduced body weight and the levels of plasma TG, prevented impairment of endothelium-dependent relaxation in HFD-fed rats. In PA-injured HUVECs, physcion inhibited impaired viability, apoptosis and inflammation. Physcion also suppressed PA-induced both oxidative stress and ER stress in HUVECs. Furthermore, physcion increased PA-induced decrease in the activation of eNOS/Nrf2 signaling in HUVECs. These findings suggest that physcion has a significant beneficial effect on regulating HFD-induced endothelial dysfunction, which may be related to the inhibition of oxidative stress and ER stress through activation of eNOS/Nrf2 signaling pathway.

A novel mouse whole blood thrombin generation assay sensitive toFXI- and FIX-mediated amplification of coagulation.

Thrombin generation (TG) assays serve as a valuable tool to study the amplifying roles of intrinsic pathway factors in human coagulation and provide functional insights into the increased bleeding observed in individuals deficient in factors (F) XI, IX, or VIII. Mice are used extensively in hemostasis research owing to the availability of coagulation factor-deficient mice. However, phenotypic differences between mouse and human TG have become apparent. In this study, we describe a novel, calibrated mouse whole blood (WB) TG assay used to assess the amplifying roles of intrinsic pathway factors in mouse coagulation. WB- and plasma-TG was triggered with either silica or tissue factor (TF) in samples from wild-type mice and mice deficient for FXII, FXI, or FIX. Expectedly, silica-triggered WB-TG and platelet-poor plasma (PPP)-TG were significantly reduced by deficiencies for FXII, FXI, or FIX. FXII deficiency had no effect on WB-TG or PPP-TG when triggered with TF. However, FXI deficiency resulted in significantly reduced WB-TG triggered by low concentrations of TF but had no effect on TF-triggered PPP-TG. FIX deficiency profoundly reduced WB-TG when triggered by low or high concentrations of TF whereas TG in PPP or platelet-rich plasma was only moderately reduced under these conditions. In conclusion, we have developed a novel mouse WB-TG assay with enhanced sensitivity to FXI- and FIX-dependent amplification of coagulation compared with an established plasma-TG assay. The enhanced sensitivity of WB-TG to FXI and FIX-dependent amplification of coagulation suggests an important role of blood cells in this process.

Effects of a Phytogenic Supplement Containing Olive By-Product and Green Tea Extracts on Growth Performance, Lipid Metabolism, and Hepatic Antioxidant Capacity in Largemouth Bass (Micropterus salmoides) Fed a High Soybean Meal Diet.

A 10-week growth trial was conducted to investigate the effects of a phytogenic feed additive (PFA) containing olive by-products and green tea extracts supplemented to a reduced fishmeal/high soybean meal diet on the growth performance, hepatic antioxidant capacity, lipid metabolism, and liver health of largemouth bass (Micropterus salmoides). Three experimental diets were tested: (1) a control high fishmeal (40%) and low soybean meal (15.57%) diet (named HFM), (2) a reduced fishmeal (30%) and high soybean meal (30.97%) diet (named HSB), and (3) a HSB diet supplemented with the PFA at 500 mg/kg (named HSB+P). Each diet was assigned to four replicate tanks, each containing 30 largemouth bass (initial body weight, IBW = 48.33 ± 0.01 g). The results showed that increasing the soybean meal content in the diet did not negatively affect growth performance, whereas supplementation with PFA significantly increased weight gain and specific growth rate of largemouth bass compared to both HFM and HSB groups. Reducing fishmeal and increasing soybean meal in the diet caused oxidative stress with a higher content of ROS in the liver. However, the hepatic antioxidant capacity was enhanced, with reduced ROS and increased GSH-Px levels in the HSB+P group. Moreover, the decrease of plasma TG, LDL-C, and LDL-C/TC, and downregulation of lipogenesis and cholesterol synthesis gene expression in liver, indicated that supplementation with the PFA improved fish lipid metabolism. Protein retention efficiency was also significantly increased in largemouth bass fed the diet with PFA supplementation, which regulated (enhanced) AKT-mTOR phosphorylation. These results clearly indicated that a PFA containing olive by-product and green tea extracts can positively improve growth performance, protein retention efficiency, antioxidant capacity, and lipid metabolism of largemouth bass fed a reduced fishmeal/high soybean meal diet.

Cholesteryl Ester Transfer Protein (CETP) I405V (rs5882) Polymorphism Affects Plasma Lipid Parameters and Lipoprotein Ratio in Hyperlipidemic Ischemic Stroke Patients

Background: High-density lipoprotein cholesterol (HDL-C) and other lipoproteins are metabolized in part by the cholesteryl ester transport protein (CETP). Cardiovascular risk and the occurrence of ischemic stroke are linked to polymorphism in the CETP gene.&#x0D; Methodology: For the study, 100 ischemic stroke patients and 100 controls with matched sexes and ages ranging from 46 to 87 were chosen. Lipoprotein ratios were computed using Excel software, and lipid parameters were evaluated using Randox diagnostic kits. Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) and 2% gel electrophoresis were used to genotype the CETP gene. The genotyping of the CETP gene were performed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) combined with 2% gel electrophoresis.&#x0D; Results: There were significant difference (P&lt;0.0001) in the genotypic and allelic frequencies of CETP SNP between the healthy and patients with ischemic stroke. The frequencies of I/I, I/V and V/V genotypes of the CETP gene were 48%, 37% and 15% for the control and 17%, 33% and 50%, for the stroke subjects, respectively. The frequencies of I and V alleles were 67% and 33% for the control and 37.5% and 62.5% for the stroke subjects, respectively. The V allele carriers of CETP gene had higher plasma TC, TG, VLDL-C, LDL-C, Non-HDL-C, defective HDL-C, HDL2-C and HDL3-C when compared to the I allele carriers for both subjects. The V allele carriers were responsible for the increase in dyslipidemia for both subjects.&#x0D; Conclusion: The results of this study show that mutation of CETP I405V (rs5882) polymorphism causes an increased in plasma TC, TG, VLDL-C, LDL-C, Non-HDL-C, defective HDL-C, HDL2-C and HDL3-C concentration and is associated with an increased risk of ischemic stroke.

Walking Exercise Reduces Postprandial Lipemia but Does Not Influence Postprandial Hemorheological Properties and Oxidative Stress.

A higher postprandial triglycerides response and hemorheological abnormalities may increase the incidence of metabolic disorders and negatively interfere with the aging process. A single session of preprandial endurance exercise was found to be effective in reducing triglyceride levels after a high-fat diet. However, whether the exercise-induced reduction in postprandial triglyceride levels influences hemorheological indicators remains unknown. This study aims to investigate the effects of postprandial lipemia on hemorheological properties and oxidative stress. Eight healthy young male participants completed two experimental trials. On day 1, the participants were randomly assigned to walk for 1 h at 50% VO2max (EE trial) or rest (CON trial). On day 2, participants rested and consumed a high-fat meal in the morning. Results: The postprandial area under the curve (AUC) of plasma TG concentration was significantly lower in EE compared to CON (EE: 9.2 ± 1.9; CON: 10.9 ± 1.7 mmol/L·h−1; p = 0.013; Cohen’s d = 0.036). No significant difference was observed in hemorheological properties and MDA (p > 0.05). Endurance exercise effectively decreased postprandial TG concentration but did not influence the postprandial hemorheological properties and oxidative stress indicators.

Ethyl EPA and ethyl DHA cause similar and differential changes in plasma lipid concentrations and lipid metabolism in subjects with low-grade chronic inflammation

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to similarly lower plasma TG concentrations but differentially regulate plasma LDL-C and HDL-C concentrations. The aim of this study was to evaluate the common and differential effects of these ω-3 fatty acids on plasma lipids and lipoproteins and to assess the metabolic mechanisms of the effects. In a randomized, double-blind, crossover study, we assessed the effect of 10-week supplementation with 3 g/d pure EPA and pure DHA (both as ethyl ester, ≥97% purity) on plasma lipid and lipoprotein concentrations and activities of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) in 21 older (>50 y) men and postmenopausal women with some characteristics of metabolic syndrome and low-grade chronic inflammation. Both EPA and DHA lowered plasma TG concentrations and increased LDL-C/apoB and HDL-C/apoA-I ratios, but only DHA increased LDL-C concentrations. The reductions in plasma TG were inversely associated with the changes in LPL activity after both EPA and DHA supplementation. EPA lowered CETP, while DHA lowered LCAT activity. EPA and DHA worked differently in men and women, with DHA increasing LPL activity and LDL-C concentrations in women, but not in men. EPA and DHA exerted similar effects on plasma TG, but differences were observed in LDL-C concentrations and activities of some enzymes involved in lipoprotein metabolism. It was also noted that EPA and DHA worked differently in men and women, supporting sex-specific variations in lipoprotein metabolism.

(PEFC&E 2022 Student Poster Award Winner - 3rd Place) PEFC Electrocatalysts Using Sn-Based Materials Dispersed on Mesoporous Carbon

Introduction Cathode catalysts of polymer electrolyte fuel cells (PEFCs) are subjected to a severe environment of strong acidity and high potential, leading to catalyst degradation[1]. In particular, catalyst degradation in fuel cell vehicles is often caused by oxidative corrosion of their carbon support during start-stop cycles, and by dissolution and re-deposition of platinum particles during load cycles[2]. Our research group has been studying nanocomposite catalysts (Pt-oxide) combining Pt with metal oxides (TiO2, SnO2) of a few nm in size, suppressing the aggregation and degradation of Pt catalysts during load cycles and also during start-stop cycles[3]. Here in this study, we prepare nanocomposite catalysts using SnO2 as a metal oxide, evaluate their electrochemical performance, and control support framework and heat treatment conditions to consider design guidelines for higher performance and durability of PEFC electrocatalysts. Experimental Pt-SnO2 nanocomposite electrocatalysts were prepared by the acetylacetonate (acac) method[4], in which Pt and Sn are loaded simultaneously to form nanocomposite of Pt and SnO2. This study used mesoporous carbon (MC) with 10 nm diameter mesopores as a support framework to impregnate the nanocomposite within the mesopores. The loading of Pt-SnO2 was 42 wt.%, and the volume ratio of Pt:SnO2 was 1:2. Loadings of Pt and SnO2 in the prepared Pt-SnO2/MC were confirmed by Inductively coupled plasma atomic emission spectroscopy (ICP-AES) and TG analysis. Microstructure was observed by STEM. The initial activity and durability of the electrocatalysts were evaluated by half-cell measurements. Results and discussion ICP-AES and TG analysis of the prepared Pt-SnO2/MC confirmed that Pt-SnO2 nanocomposite was loaded at a volume ratio of Pt:SnO2=1:2, which was close to the designated ratio. EDS elemental analysis confirmed the presence of Sn between the Pt particles, suggesting the formation of a nanocomposite structure. STEM microstructural observation confirmed that catalyst particles were loaded inside the mesopores besides on MC (agglomerate) surfaces. The ratio of internal particles was 55 %. The obtained catalyst was subjected to load cycle tests (100,000 cycles), and was found to be more durable in catalytic activity. In this presentation, electrochemical properties using related materials will be presented. Acknowledgment This research was partly supported by the New Energy and Industrial Technology Development Organization (NEDO).

Potential novel biomarkers in small intestine for obesity/obesity resistance revealed by multi-omics analysis

BackgroundAlthough obesity is caused by different factors, individual susceptibility to obesity differs among people under the same circumstances. The microbiota in the caecum or fresh faeces and metabolites in blood or urine contribute to obesity resistance; however, the microbiota or metabolites in the small intestine have not been extensively studied.MethodsTo investigate the relationship between the microbiota or metabolites in the small intestine and susceptibility to obesity, eighty-eight male C57BL/6 mice were fed a high-fat diet (HFD) for 8 weeks to establish two models of obesity and obesity resistance. For further study, six mice were chosen from among the obesity models, and twelve mice were randomly chosen from among the obesity resistance models. After fasting plasma glucose and behavioural testing, the mice were fed in single cages for another 4 weeks to observe their weight and food intake. All mice were sacrificed at 20 weeks of age. Serum ALT, AST, HDL, LDL, TG and TC levels were measured using an automatic biochemical analyser. The microbiota and metabolites in the small intestine contents were analysed using 16 S sequencing and an ultrahigh-performance liquid chromatographic system, respectively. Transcripts in the jejunum were evaluated using full-length transcriptome sequencing and verified by qPCR.ResultsThe results showed that HFD induced depression and anxiety behaviours and higher fasting plasma glucose, ALT, AST, HDL, LDL, TG and TC levels in the obese mice; however, these levels were improved in obese resistance mice. The correlation analysis showed that the phosphatidylcholine, TG, and phosphatidylethanolamine levels were higher in obese mice and correlated positively with intestinal microflora (Desulfovibrio and Gemella) and the Cxcl10 gene. A higher abundance of Clostridium_sensu_stricto_1 in obesity-resistant mice correlated negatively with the metabolite contents (neuromedin N and enkephalin L) and Pck1 gene expression and correlated positively with certain metabolites (5-hydroxy-L-tryptophan, cinnamyl alcohol and 1 H-indole-3-acetamide) and genes expression (Gdf15, Igfbp6 and Spp1).ConclusionClostridium_sensu_stricto_1, neuromedin N, enkephalin L, Pck1, 5-hydroxy-L-tryptophan, Cxcl10 and cinnamyl alcohol may be novel biomarkers in the small intestine for obesity/obesity resistance. These might be helpful for obesity prevention or for treating obese patients.

Altered Cord Blood Lipid Concentrations Correlate with Birth Weight and Doppler Velocimetry of Fetal Vessels in Human Fetal Growth Restriction Pregnancies.

Fetal growth restriction (FGR) is associated with short- and long-term morbidity, often with fetal compromise in utero, evidenced by abnormal Doppler velocimetry of fetal vessels. Lipids are vital for growth and development, but metabolism in FGR pregnancy, where fetuses do not grow to full genetic potential, is poorly understood. We hypothesize that triglyceride concentrations are increased in placentas and that important complex lipids are reduced in cord plasma from pregnancies producing the smallest babies (birth weight < 5%) and correlate with ultrasound Dopplers. Dopplers (umbilical artery, UA; middle cerebral artery, MCA) were assessed longitudinally in pregnancies diagnosed with estimated fetal weight (EFW) < 10% at ≥29 weeks gestation. For a subset of enrolled women, placentas and cord blood were collected at delivery, fatty acids were extracted and targeted lipid class analysis (triglyceride, TG; phosphatidylcholine, PC; lysophosphatidylcholine, LPC; eicosanoid) performed by LCMS. For this sub-analysis, participants were categorized as FGR (Fenton birth weight, BW ≤ 5%) or SGA “controls” (Fenton BW > 5%). FGRs (n = 8) delivered 1 week earlier (p = 0.04), were 29% smaller (p = 0.002), and had 133% higher UA pulsatility index (PI, p = 0.02) than SGAs (n = 12). FGR plasma TG, free arachidonic acid (AA), and several eicosanoids were increased (p < 0.05); docosahexaenoic acid (DHA)-LPC was decreased (p < 0.01). Plasma TG correlated inversely with BW (p < 0.05). Plasma EET, non-esterified AA, and DHA correlated inversely with BW and directly with UA PI (p < 0.05). Placental DHA-PC and AA-PC correlated directly with MCA PI (p < 0.05). In fetuses initially referred for inadequate fetal growth (EFW < 10%), those with BW ≤ 5% demonstrated distinctly different cord plasma lipid profiles than those with BW > 5%, which correlated with Doppler PIs. This provides new insights into fetal lipidomic response to the FGR in utero environment. The impact of these changes on specific processes of growth and development (particularly fetal brain) have not been elucidated, but the relationship with Doppler PI may provide additional context for FGR surveillance, and a more targeted approach to nutritional management of these infants.

GLP-1 attenuates intestinal fat absorption and chylomicron production via vagal afferent nerves originating in the portal vein

Background/ObjectiveGLP-1R agonists have been shown to reduce fasting and postprandial plasma lipids, both of which are independent risk factors for the development of cardiovascular disease. However, how endogenous GLP-1 – which is rapidly degraded – modulates intestinal and hepatic lipid metabolism is less clear. A vagal gut-brain-axis originating in the portal vein has been proposed as a possible mechanism for GLP-1’s anti-lipemic effects. Here we sought to examine the relationship between vagal GLP-1 signalling and intestinal lipid absorption and lipoprotein production. MethodsSyrian golden hamsters or C57BL/6 mice received portal vein injections of GLP-1(7-36), and postprandial and fasting plasma TG, TRL TG, or VLDL TG were examined. These experiments were repeated during sympathetic blockade, and under a variety of pharmacological or surgical deafferentation techniques. In addition, hamsters received nodose ganglia injections of a GLP-1R agonist or antagonist to further probe the vagal pathway. Peripheral studies were repeated in a novel GLP-1R KO hamster model and in our diet-induced hamster models of insulin resistance. ResultsGLP-1(7-36) site-specifically reduced postprandial and fasting plasma lipids in both hamsters and mice. These inhibitory effects of GLP-1 were investigated via pharmacological and surgical denervation experiments and found to be dependent on intact afferent vagal signalling cascades and efferent changes in sympathetic tone. Furthermore, GLP-1R agonism in the nodose ganglia resulted in markedly reduced postprandial plasma TG and TRL TG, and fasting VLDL TG and this nodose GLP-1R activity was essential for portal GLP-1s effect. Notably, portal and nodose ganglia GLP-1 effects were lost in GLP-1R KO hamsters and following diet-induced insulin resistance. ConclusionOur data demonstrates for the first time that portal GLP-1 modulates postprandial and fasting lipids via a complex vagal gut–brain–liver axis. Importantly, loss or interference with this signalling axis via surgical, pharmacological, or dietary intervention resulted in the loss of portal GLP-1s anti-lipemic effects. This supports emerging evidence that native GLP-1 works primarily through a vagal neuroendocrine mechanism.