Increase In Triglyceride Content Research Articles

Genetically mimicked effects of evinacumab on psoriasis: a drug target Mendelian randomization study.

Dyslipidemia has been reported to contribute to the psoriasis pathogenesis. Thus, evinacumab, a novel lipid-lowering drug targeting angiopoietin-like 3, may have therapeutic potential to treat and/or manage psoriasis. Summary statistics were obtained from genome-wide association studies addressing psoriasis (FinnGen Consortium; n=216,752) and serum lipid concentrations (United Kingdom Biobank; n=403,943-440,546). Two-sample Mendelian randomization analyses were conducted to evaluate the associations of serum lipid concentrations and genetically mimicked effects of evinacumab, respectively, with the risks of psoriasis and its subtypes. Genetically determined per standard deviation increase in triglyceride concentrations was associated with increased risk of psoriasis (OR: 1.17, 95% CI: 1.03-1.32, p=0.018), whereas that in low-density lipoprotein-cholesterol (LDL-C) was associated with both psoriasis (OR: 1.22, 95% CI: 1.05-1.43, p=0.011) and its subtypes, including arthropathic psoriasis (OR: 1.30, 95% CI: 1.02-1.65, p=0.032), psoriasis vulgaris (OR: 1.87, 95% CI: 1.16-2.99, p=0.0095), and guttate psoriasis (OR: 2.19, 95% CI: 1.17-4.07, p=0.014). Moreover, genetically mimicked effects of evinacumab, via angiopoietin-like 3 inhibition, significantly reduced the risk of psoriasis (OR: 0.752 per standard deviation reduction in triglycerides, 95% CI: 0.577-0.982, p=0.036) and arthropathic psoriasis (OR: 0.266 per standard deviation reduction in LDL-C, 95% CI: 0.0886-0.799, p=0.018). The genetically mimicked effect of evinacumab has the potential to reduce the risk of psoriasis and arthropathic psoriasis by lowering circulating triglyceride and LDL-C concentrations, respectively. These findings suggest that evinacumab may help prevent psoriasis and psoriatic arthritis progression in clinical practice.

Impact of Soybean Bioactive Peptides on Growth, Lipid Metabolism, Antioxidant Ability, Molecular Responses, and Gut Microbiota of Oriental River Prawn (Macrobrachium nipponense) Fed with a Low-Fishmeal Diet.

The substitution of fishmeal with high-level soybean meal in the diet of crustaceans usually induces lipid accumulation and oxidative stress in the hepatopancreas. Therefore, it is essential to alleviate these adverse effects. In the present study, SBPs were used to alleviate the negative effects of a fishmeal decrease on the growth performance, lipid metabolism, antioxidant capacity, and gut microbiota of oriental river prawn (Macrobrachium nipponense) in an 8-week feeding trial. Three isonitrogenic and isolipidic diets were prepared as follows: R (reference diet with 32% fishmeal), CT (control diet with 22% fishmeal), and SBP (22% fishmeal with 1.25 g/kg soybean bioactive peptides). The prawns (initial biomass per tank 17 g) were randomly divided into three groups with four replicates. The results showed that the low-fishmeal diet induced the following: (1) the inhibition of growth performance and survival of prawns; (2) an increase in triglyceride content in the hepatopancreas and hemolymph and downregulation of carnitine palmitoyl transferase 1 (cpt1) gene expression; (3) a reduction in antioxidant enzymes' activities and their genes expression levels and an increase malondialdehyde (MDA) content; and (4) an increase in the abundance of the conditional pathogen Pseudomonas in the gut. SBPs supplementation in the CT diet effectively alleviated most of the above adverse effects. SBPs enhanced inducible nitric oxide synthase (iNOS) activity to synthesize nitric oxide (NO) by activating the imd-relish pathway. Most importantly, SBPs increased the potential probiotic Rikenellaceae_RC9_gut_group abundance and decreased the abundance of the conditional pathogen Pseudomonas in the gut. In conclusion, SBPs supplementation can improve low-fishmeal-diet-induced growth inhibition by regulating the gut microbiota composition to ameliorate lipid deposition and oxidative stress and strengthen immune status in oriental river prawn.

Alcoholic Extracts from the Ganoderma Lucidum Fermentation Product Alleviated Ethanol-Induced Liver Injury, Gut Leakiness, and Gut Dysbiosis in Mice.

The hepatoprotective effect of the alcoholic extracts of Ganoderma lucidum fermentation products (GFE) was investigated. C57BL/6 mice were pretreated with GFE for 7 days and then subjected to the chronic-binge ethanol feeding model. GFE pretreatment significantly reduced the ethanol-induced elevated serum levels of aspartate aminotransferase (AST) and alanine transaminase (ALT), hepatic steatosis, and increased triglyceride content. GFE pretreatment also altered hepatic alcohol metabolism, suppressed oxidative stress by decreasing the expression of Cyp2e1, and increasing the level of GSH. Lipidmoic analysis revealed that GFE pretreatment effectively increased ratio of phosphatidylcholines /phosphatidylethanolamine (PC/PE) in the liver. Furthermore, mice pretreated with GFE demonstrated decreased hepatic inflammation and plasma lipopolysaccharide (LPS) levels. Additionally, the mRNA expression of gut tight junction proteins such as ZO-1, Occludin and Claudin-1, along with antimicrobial peptide (e.g., Reg3β and Reg3γ) were up-regulated by GFE pretreatment. 16s rRNA sequencing revealed that GFE increased Bacteroidales, Parabacteroides, and Dubosiella, which were associated with hepatic steatosis, inflammation and intestinal barrier function parameters. These results demonstrate that GFE can prevent ethanol-induced liver injury and inflammation, gut leakiness and restore gut microbiota dysbiosis.

Curcumin Nicotinate Activates AMPK to Inhibit Aerobic Glycolysis in Vascular Endothelial Cells to Prevent Restenosis

Abnormal proliferation of vascular smooth muscle cells (VSMCs) participates in restenosis after percutaneous coronary intervention (PCI). Curcumin, as the main active ingredient of turmeric, has been proven to inhibit the abnormal proliferation of VSMCs. This study intends to identify the mechanism whereby curcumin nicotinate (CurTn) protects against vascular restenosis. The expression of PTEN and PFKFB3 in VSMCs was detected by immunofluorescence and Western blot. Glycolysis in VSMCs was evaluated by detecting ECAR expression and MTT assays, whilst the Tandem Mass Tag (TMT)-based Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) determined expression of AMPK/PTEN/PFKFB3 in glycolysis. After treatment with CurTn, intracellular citrate and acetyl-CoA levels, and expression of triglyceride content were measured. PFKFB3 and PTEN was up-regulated in the carotid artery specimen. Overexpression of PTEN induced abnormal proliferation of VSMCs and promoted the phenotype conversion of VSMCs when increasing PFKFB3 expression. Additionally, while overexpression of AMPK did not up-regulate PFKFB3 expression, silencing of AMPK prevented the increase in PFKFB3 expression induced by PTEN. Treatment with CurTn enhanced glycolysis and increased the expression level of citrate, acetyl-CoA, and triglycerides. Importantly, PTEN overexpression increased PFKFB3 KD and PFK158 expression and alleviated CurTn-induced increase in triglyceride content. CurTn effectively delays the process of vascular restenosis through AMPK/PTEN/PFKFB3 pathway to inhibit aerobic glycolysis and VSMC proliferation.

Association Between Hyperlipidaemia and Selected Cholestatic Markers in 74 Dogs with Suspect Acute Pancreatitis.

The association between hyperlipidaemia and acute pancreatitis is unknown in dogs. This study aimed to investigate the association between hyperlipidaemia and other markers of cholestasis in dogs with suspect acute pancreatitis. Case records of dogs with suspect acute pancreatitis were retrospectively reviewed. Dogs that had pre-existing disorders or drug therapies associated with hyperlipidaemia, hypocholesterolaemia, or incomplete biochemical data were excluded. In total, 74 dogs met the inclusion criteria. There were 33 (44.6%) dogs with hypercholesterolaemia (HC) and 41 (55.4%) without (NC). Increased triglyceride concentrations were significantly (p = 0.005) more common in HC dogs (n = 13, 39.4%) compared with NC dogs (n = 4, 9.8%), but no value exceeded 5 mmol/L. The ALP activity was significantly higher in the HC group compared to NC group (932 (461-7271) and 380 (135-1312) IU/L, respectively, p = 0.001). There was a moderate positive correlation between cholesterol concentration and ALP activity (r = 0.498, p < 0.001) and a weak positive correlation between cholesterol concentration and gamma-glutamyl transferase activity (r = 0.296, p = 0.011). Cholesterol concentration was correlated with ALP and GGT activities suggesting an association between cholestasis and hypercholesterolaemia in dogs with acute pancreatitis.

TOMM40 regulates hepatocellular and plasma lipid metabolism via an LXR-dependent pathway

ObjectiveThe gene encoding TOMM40 (Transporter of Outer Mitochondrial Membrane 40) is adjacent to that encoding APOE, which has a central role in lipid and lipoprotein metabolism. While human genetic variants near APOE and TOMM40 have been shown to be strongly associated with plasma lipid levels, a specific role for TOMM40 in lipid metabolism has not been established, and the present study was aimed at assessing this possibility. MethodsTOMM40 was knocked down by siRNA in human hepatoma HepG2 cells, and effects on mitochondrial function, lipid phenotypes, and crosstalk between mitochondria, ER, and lipid droplets were examined. Additionally, hepatic and plasma lipid levels were measured in mice following shRNA-induced knockdown of Tomm40 shRNA. ResultsIn HepG2 cells, TOMM40 knockdown upregulated expression of APOE and LDLR in part via activation of LXRB (NR1H2) by oxysterols, with consequent increased uptake of VLDL and LDL. This is in part due to disruption of mitochondria-endoplasmic reticulum contact sites, with resulting accrual of reactive oxygen species and non-enzymatically derived oxysterols. With TOMM40 knockdown, cellular triglyceride and lipid droplet content were increased, effects attributable in part to receptor-mediated VLDL uptake, since lipid staining was significantly reduced by concomitant suppression of either LDLR or APOE. In contrast, cellular cholesterol content was reduced due to LXRB-mediated upregulation of the ABCA1 transporter as well as increased production and secretion of oxysterol-derived cholic acid. Consistent with the findings in hepatoma cells, in vivo knockdown of TOMM40 in mice resulted in significant reductions of plasma triglyceride and cholesterol concentrations, reduced hepatic cholesterol and increased triglyceride content, and accumulation of lipid droplets leading to development of steatosis. ConclusionsThese findings demonstrate a role for TOMM40 in regulating hepatic lipid and plasma lipoprotein levels and identify mechanisms linking mitochondrial function with lipid metabolism.

A-226 Validation of Calculated Glycerol Corrected Triglycerides

Abstract Background Patients with elevated free glycerol can have falsely elevated triglyceride concentrations known as pseudohypertriglyceridemia. Most clinical laboratory triglycerides methods measure the concentration of glycerol released following the enzymatic hydrolysis of triglycerides to quantitate triglycerides. Thus, increased free glycerol can lead to falsely increased triglyceride concentration. Identifying and measuring the interference is necessary to effectively manage patient care interventions. A glycerol-corrected triglyceride assay was discontinued from Roche Diagnostics in 2021. We created a process to determine glycerol-corrected triglycerides by measuring glycerol directly using an assay from Randox Laboratories. Methods Glycerol (Randox Laboratories) and nonglycerol-blanked triglycerides (Roche Diagnostics) were measured in serum using the Roche Cobas c501. Stability (n=10) and expected values (n=206) were determined using serum from healthy volunteers. Linearity (n=5) and precision (5 replicates on 2 runs over 5 days) were determined using residual clinical serum spiked with exogenous glycerol as necessary to span the analytical measuring range. Glycerol corrected triglyceride concentrations were calculated by subtracting glycerol (mmol/L) from triglyceride (mmol/L) and converting to mg/dL (x88.59). Samples previously measured using the Triglyceride/Glycerol Blanked Reagent (n=53, Roche Diagnostics) were used to assess accuracy. (Figure 1) Results Glycerol measures were stable 3 days refrigerated and 30 days frozen. Precision coefficient of variation was 1.0% within run and 7.1% within lab. Expected values were 10 - 109 mcmol/L, and the method was linear between 2 - 3,971 mcmol/L. The average bias between methods was 11.0% with slope of 1.02 and R2&amp;gt;0.97 (Figure 1). Conclusions Glycerol can be accurately measured using the Randox method and the result can be used to generate an accurate glycerol-corrected triglyceride concentration.

Acute waterborne cadmium exposure induces liver ferroptosis in Channa argus

The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe2+, ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.

Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights from Genetic and Experimental Models.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without effective medications. This study integrated genetic, proteomic, and metabolomic data to identify causation between increased triglyceride (TG)-rich lipoproteins and AAA risk. Three hypertriglyceridemia mouse models were employed to test the hypothesis that increased plasma TG concentrations accelerate AAA development and rupture. In the angiotensin II-infusion AAA model, most Lpl -deficient mice with severely high plasma TG concentrations died of aortic rupture. Consistently, Apoa5 -deficient mice with moderately increased TG concentrations had accelerated AAA development, while human APOC3 transgenic mice with dramatically increased TG concentrations exhibited aortic dissection and rupture. Increased TG concentrations and palmitate inhibited lysyl oxidase maturation. Administration of antisense oligonucleotide targeting Angptl3 profoundly inhibited AAA progression in human APOC3 transgenic mice and Apoe -deficient mice. These results indicate that hypertriglyceridemia is a key contributor to AAA pathogenesis, highlighting the importance of triglyceride-rich lipoprotein management in treating AAA.

Identification of nutrition factors in the metabolic syndrome and its progression over time in older adults: analysis of the TUDA cohort

BackgroundNutrition is recognized as playing an important role in the metabolic syndrome (MetS), but the dietary components involved are unclear. We aimed to investigate nutrition factors in relation to MetS and its progression in older adults over a follow-up period of 5.4 years.MethodsCommunity-dwelling adults (≥ 60y) from the Trinity-Ulster-Department-of-Agriculture study, sampled at baseline (2008–12) and follow-up (2014–18; n 953), were classified as ‘with MetS’ by having three or more of: waist circumference (≥ 102 cm, males; ≥ 88 cm, females); HDL-cholesterol (< 1.0 mmol/L, males; < 1.3 mmol/L, females); triglycerides (≥ 1.7 mmol/L); blood pressure (systolic ≥ 130 and/or diastolic ≥ 85 mmHg); and hemoglobin A1c (≥ 39 mmol/mol).ResultsMetS was identified in 67% of participants, increasing to 74% at follow-up. Predictors at baseline for the development of metabolic syndrome (MetS) at follow-up were higher waist circumference (odds ratio [95%CI]; 1.06 [1.01–1.11]), but not BMI, and increased triglyceride concentrations (2.01 [1.29–3.16]). In dietary analysis (at follow-up), higher protein (g/kg bodyweight/day) and monounsaturated fatty acid (g/day) intakes were each associated with lower risk of MetS (0.06 [0.02–0.20] and 0.88 [0.78–1.00], respectively), whilst higher protein was also associated with lower abdominal obesity (0.10 [0.02–0.51]) and hypertension (0.22 [0.00–0.80]). Furthermore, participants with, compared to without, MetS consumed less high-quality protein foods (P = 0.006) and more low-quality protein foods (P < 0.001), as defined by the protein digestibility-corrected amino acid score.ConclusionsDietary interventions targeting protein quantity and quality may have specific benefits in preventing or delaying the progression of MetS in at-risk older people, but this requires investigation in the form of randomized trials.

Clinical effects and adverse effects of intravenous lipid emulsion treatment in dogs and cats with suspected poisoning.

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8-12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides.

Integrated analysis of transcriptomic and physiological responses to cold stress in Macrobrachium rosenbergii

The giant freshwater prawn (GFP), Macrobrachium rosenbergii, stands out as a vital species in freshwater shrimp aquaculture. However, its susceptibility to cold conditions has increased the cost of aquaculture and limited the growth of GFP cultivation. To furnish insights at the molecular level to enhance GFP's cold tolerance, transcriptome sequencing and physiological analysis of the hepatopancreas were performed in our study. Initially, we identified 4909 differentially expressed genes (DEGs) between experimental (15 °C, 24 h) and control groups (25 °C, 24 h). These DEGs were significantly enriched in the proteasome, spliceosome, lysosome, peroxisome, and lipid metabolism-related pathways including glycerolipid metabolism, sphingolipid metabolism, linoleic acid metabolism as well as steroid hormone biosynthesis. Histological examination following various stress durations revealed a notable increase in hepatocyte vacuoles after 6 h of cold stress. Hepatocyte structure deterioration occurred in the later phase (48 h), coinciding with a significant increase in cell apoptosis. Subsequent analyses demonstrated an initial increase followed by a decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) content, while malonaldehyde (MDA) content rose with stress duration. Furthermore, a significant increase in triglyceride content and no significant change in cholesterol content was observed. RT-qPCR results unveiled significant down-regulated expression of FAS, TAGL, ACOX1, ACS and significant up-regulated expression of GPAT and DEGS. These findings suggest that oxidative stress and impaired lipid metabolism underlie the poor cold tolerance of GFP.

Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma

Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Importantly, the concurrent inhibition of MYC signaling and glutamine metabolism prevented LD accumulation and reduced tumor burden in vivo. Furthermore, we identified the hypoxia-inducible lipid droplet-associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples postulated HILPDA as a specific ccRCC biomarker. Together, these results provide an attractive approach for development of alternative therapeutic interventions for the treatment of this type of renal cancer.

MiR-192-5p Ameliorates Hepatic Lipid Metabolism in Non-Alcoholic Fatty Liver Disease by Targeting Yy1.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Clarifying the molecular mechanism of lipid metabolism is crucial for the treatment of NAFLD. We examined miR-192-5p levels in the livers of mice in which NAFLD was induced via a high-fat diet (HFD), as well as in mouse primary hepatocytes and human HepG2 cells treated with free fatty acids (FFAs). MiR-192-5p inhibitor was administered to NAFLD mice and hepatocytes to verify the specific function of miR-192-5p in NAFLD. We validated the target gene of miR-192-5p and further illustrated the effects of this miRNA on the regulation of triglyceride (TG) metabolism. We found that miR-192-5p was significantly increased in the livers of NAFLD mice and FFA-treated hepatocytes. Inhibition of miR-192-5p increased the accumulation of hepatic TGs and aggravated hepatic steatosis in NAFLD mice. In FFA-treated hepatocytes, miR-192-5p inhibitors markedly increased TG content, whereas overexpression of miR-192-5p reduced TG levels. Yin Yang 1 (Yy1) was identified as the target gene of miR-192-5p, which regulates TG synthesis via the YY1/fatty-acid synthase (FASN) pathway. Our results demonstrated that miR-192-5p should be considered a protective regulator in NAFLD that can inhibit hepatic TG synthesis by targeting Yy1.

Impact of early posthatch feeding on the immune system and selected hematological, biochemical, and hormonal parameters in broiler chickens

Under commercial conditions, chicks hatch within a 24 to 48 h window, a period known as the hatching window. Subsequently, they undergo various treatments before finally being transported to the broiler farm. These procedures may delay the chicks' access to food and water, sometimes receiving them as late as 72 h after hatching. Previous studies have indicated that fasting during this initial period is detrimental, leading to impaired body growth, compromised immune system response, and hindered muscle development. The objective of this study was to assess the impact of early posthatch feeding on immune system organs and selected hematological, biochemical, and hormonal parameters. The experiment utilized Ross 308 broiler eggs incubated under typical commercial hatchery conditions. The experimental group's eggs were hatched in HatchCare hatchers (HC) with immediate access to feed and water, while the control group's eggs were hatched under standard conditions (ST). Thirty chickens from each group were assessed on the 1st (D1), 7th (D7), 21st (D21), and 35th (D35) day after hatching. On D1, the HC group exhibited lower hemoglobin, hematocrit, and total serum protein values, suggesting that early access to water prevents initial dehydration in newborn chicks. Conversely, the ST group showed a stress reaction on D1 due to feed deprivation, leading to an almost 2-fold higher serum corticosterone concentration compared to the HC group. However, this increase did not result in a significant change in the heterophil/lymphocyte ratio. Furthermore, the HC group displayed an increase in triglyceride concentration and a decrease in HDL concentration on D1. On D7, the HC group exhibited an increased relative weight of the bursa and a higher CD4+ cell number in the cecal tonsil (CT), indicating a more rapid development of these organs resulting from early stimulation of the gastrointestinal tract. However, early feeding did not influence the numbers of Bu-1+, CD4+, and CD8+ cells or the germinal center (GC) areas in the spleen. In conclusion, early feeding contributes to the welfare of newborn chicks by reducing dehydration and stress levels and stimulating the development of gut-associated lymphoid tissue.

Oral sugar test responses to ertugliflozin in ten horses with insulin dysregulation

SummaryBackgroundPreliminary evidence indicates that ertugliflozin benefits horses and ponies (hereafter collectively referred to as horses) with hyperinsulinaemia and hyperinsulinaemia‐associated laminitis. The effects of ertugliflozin on the results of the oral sugar test used widely in the assessment of insulin dysregulation (ID), have not been reported.ObjectivesTo report the effects of ertugliflozin on responses to the oral sugar test (OST) in horses with ID.Study designRetrospective case series.MethodsClinical records were reviewed to identify horses with ID that had an OST (0.45 mL/kg Karo‐Light PO) performed before and after 4 days of treatment with 0.05 mg/kg ertugliflozin PO s.i.d. Pre‐ and post‐treatment insulin concentrations were compared using Wilcoxon sign‐ranked tests.ResultsTen horses with ID met the inclusion criteria. Significant reductions in plasma insulin concentration were identified at all time points after 4 days of treatment with ertugliflozin relative to pre‐treatment values. At T0 (prior to oral sugar), median insulin concentration reduced from 22.4 μu/mL (IQR: 6.5, 39) pre‐treatment to 4.8 μu/mL (IQR: 3.7, 9.2) at day 4 (p = 0.004). At T60 (60 min after oral sugar), median insulin concentration was 165 μu/mL (IQR: 61.2, 222) pre‐treatment and 78.1 μu/mL (IQR: 30.5, 137) at day 4 (p = 0.004). At T90 (90 min after oral sugar), median insulin concentration was 170 μu/mL (IQR: 88.6, 269) pre‐treatment and 84.7 μu/mL (IQR: 28.7, 122) at day 4 (p = 0.002). Serum triglyceride concentration increased from a median of 0.4 mmol/L (IQR: 0.2, 0.8) pre‐treatment to 0.9 mmol/L (IQR: 0.6, 2) at day 4 of ertugliflozin treatment (p = 0.006).Main limitationsA small heterogenous group of horses and ponies, some with PPID, were used in the absence of a control group.ConclusionsFour daily doses of ertugliflozin at 0.05 mg/kg was associated with lowering of insulin concentrations at baseline and in response to an OST in horses with ID; however, insulin levels did not return to normal in all horses. Increases in triglyceride concentrations were also observed.

221 Increasing Functional Amino Acid Ratios Does Not Improve Growth Performance in Pigs Raised Under Poor Sanitary Conditions When Fed with Individual Precision Feeding Or Conventional Feeding Systems

Abstract Immune system activation redirects dietary nutrients to defense mechanisms, thereby impairing growth performance of pigs. Supplementing pigs with functional amino acids (AA) such as Met, Thr and Trp was shown to support the immune system and reduce the negative effects on growth. However, pigs respond differently to immune stressors which increase herd variability. In this context, individual precision feeding (IPF) might be an alternative approach to reduce herd variability and increase nutrient efficiency in immune challenged pigs. This study aimed to evaluate growth performance, body composition, nitrogen (N) efficiency and haptoglobin and triglycerides serum concentration in growing pigs raised in poor sanitary conditions (PoorSC). The PoorSC was characterized by oral inoculation with 2 × 109 cfu of Salmonella typhimurium and manure spreading on the pen floor. Sixty gilts (23 ± 2.8 kg BW) were distributed in BW blocks according to a 2 dietary (D) × 2 feeding system (FS) factorial arrangement composed of to 2 diets [control (CN): INRA ideal AA ratio or supplemented (AA+) 120% of the ideal ratio for Met, Thr and Trp] and 2 feeding systems [conventional (GP) or IPF]. GP pigs were fed with a unique diet that matched the SID Lys requirement of the 80th-percentile pig at the beginning of the trial whereas the IPF pigs received a diet tailored daily to each pig requirement. All pigs were housed in the same pen and fed ad libitum during 28 experimental days with automatic feeding stations able to provide to each pig the assigned diet. Body composition was obtained by dual X-ray absorptiometry at days 0 and 28 and blood samples were collected at d 28. Data were analyzed with D and FS and their interaction as main fixed factors and body weight (BW) blocks as a random effect (Table 1). Haptoglobin serum concentration increased from d 0 to 28 regardless of FS and D (P &amp;lt; 0.10). IPF pigs fed with CN diet had the lightest BW at the end of the trial (P ≤ 0.10; FS × D), whereas BW was similar for the other treatments. However, across diets, IPF pigs had final BW, and protein, ADG, G:F, protein and lipid deposition, N intake and excretion and circulating triglycerides that were less than GP pigs. N utilization efficiency was similar across treatments. Additionally, increasing the provision of the studied functional AA did not improve pig performance. Thus, showing no benefits in increasing AA ratios for growth and immune response. The increased triglycerides concentration and low protein and lipid deposition suggests that IPF pigs prioritized the immune system to the expense of protein and lipid accretion. In conclusion, AA supplementation and IPF do not improve growth performance and N efficiency of pigs raised in poor sanitary conditions.

The metabolic response of human trophoblasts derived from term placentas to metformin

Aims/hypothesisMetformin is increasingly used therapeutically during pregnancy worldwide, particularly in the treatment of gestational diabetes, which affects a substantial proportion of pregnant women globally. However, the impact on placental metabolism remains unclear. In view of the association between metformin use in pregnancy and decreased birthweight, it is essential to understand how metformin modulates the bioenergetic and anabolic functions of the placenta.MethodsA cohort of 55 placentas delivered by elective Caesarean section at term was collected from consenting participants. Trophoblasts were isolated from the placental samples and treated in vitro with clinically relevant doses of metformin (0.01 mmol/l or 0.1 mmol/l) or vehicle. Respiratory function was assayed using high-resolution respirometry to measure oxygen concentration and calculated {dot{V}mathrm{O}}_{2}. Glycolytic rate and glycolytic stress assays were performed using Agilent Seahorse XF assays. Fatty acid uptake and oxidation measurements were conducted using radioisotope-labelled assays. Lipidomic analysis was conducted using LC-MS. Gene expression and protein analysis were performed using RT-PCR and western blotting, respectively.ResultsComplex I-supported oxidative phosphorylation was lower in metformin-treated trophoblasts (0.01 mmol/l metformin, 61.7% of control, p<0.05; 0.1 mmol/l metformin, 43.1% of control, p<0.001). The proton efflux rate arising from glycolysis under physiological conditions was increased following metformin treatment, up to 23±5% above control conditions following treatment with 0.1 mmol/l metformin (p<0.01). There was a significant increase in triglyceride concentrations in trophoblasts treated with 0.1 mmol/l metformin (p<0.05), particularly those of esters of long-chain polyunsaturated fatty acids. Fatty acid oxidation was reduced by ~50% in trophoblasts treated with 0.1 mmol/l metformin compared with controls (p<0.001), with no difference in uptake between treatment groups.Conclusions/interpretationIn primary trophoblasts derived from term placentas metformin treatment caused a reduction in oxidative phosphorylation through partial inactivation of complex I and potentially by other mechanisms. Metformin-treated trophoblasts accumulate lipids, particularly long- and very-long-chain polyunsaturated fatty acids. Our findings raise clinically important questions about the balance of risk of metformin use during pregnancy, particularly in situations where the benefits are not clear-cut and alternative therapies are available.Graphical

Sensing of triglyceride concentration in blood solution using photoacoustic microscopy.

The level of triglyceride (TG) in blood is essential to human health, and hypertriglyceridemia (TG level > 150 mg/dL) would lead to cardiovascular disease and acute pancreatitis that threaten human life. Routine methods for measuring the TG level in blood depend on a lipid panel blood test, which is invasive and not convenient. Here, we use photoacoustic (PA) microscopy to test the PA amplitude of blood solutions (based on hemoglobin powder as well as flowing sheep blood) with different TG concentrations. Interestingly, we observe that the PA amplitude increases with increasing TG concentration in blood solutions, which is attributed to the increase of the Grüneisen coefficient. The preliminary in vitro study shows that the PA methodology is able to detect the TG level down to 450 mg/dL. This finding provides an opportunity for using photoacoustics to noninvasively diagnose hypertriglyceridemia.

Neonatal administration of fenofibrate had no developmental programming effect on the lipid profile and relative leucocyte telomere lengths of adolescent rats fed a high-fructose diet postnatally.

Telomere length, a marker of ageing, is susceptible to developmental programming that may cause its accelerated attrition. Metabolic syndrome triggers telomere attrition. Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, is protective against telomere attrition. We investigated the impact of fenofibrate administered during suckling on the lipid profile and leucocyte telomere lengths of rats fed a high-fructose diet post-weaning. Suckling Sprague-Dawley pups (n=119) were allocated to four groups and gavaged with either 10mL·kg-1 body mass 0.5% dimethyl sulfoxide, 100mg·kg-1 body mass fenofibrate, fructose (20%, w / v), or a combination of fenofibrate and fructose for 15 days. Upon weaning, each of the initial groups was split into two subgroups: one had plain water while the other had fructose solution (20%, w / v) to drink for 6 weeks. Blood was collected for DNA extraction and relative leucocyte telomere length determination by real-time PCR. Plasma triglycerides and cholesterol were also quantified. The treatments had no effect (p>0.05) on body mass, cholesterol concentration, and relative leucocyte telomere lengths in both sexes. Post-weaning fructose increased triglyceride concentrations (p<0.05) in female rats. Fenofibrate administered during suckling did not affect ageing nor did it prevent high fructose-induced hypertriglyceridaemia in female rats.