Triglyceride Concentrations Research Articles

Oxysterol-binding protein-like 7 deficiency leads to ER stress-mediated apoptosis in podocytes and proteinuria.

Chronic kidney disease (CKD) is associated with renal lipid dysmetabolism among a variety of other pathways. We recently demonstrated that oxysterol-binding protein-like 7 (OSBPL7) modulates the expression and function of ATP-binding cassette subfamily A member 1 (ABCA1) in podocytes, a specialized type of cell essential for kidney filtration. Drugs that target OSBPL7 lead to improved renal outcomes in several experimental models of CKD. However, the role of OSBPL7 in podocyte injury remains unclear. Using mouse models and cellular assays, we investigated the influence of OSBPL7 deficiency on podocytes. We demonstrated that reduced renal OSBPL7 levels as observed in two different models of experimental CKD are linked to increased podocyte apoptosis, primarily mediated by heightened endoplasmic reticulum (ER) stress. Although as expected, the absence of OSBPL7 also resulted in lipid dysregulation (increased lipid droplets and triglycerides content), OSBPL7 deficiency-related lipid dysmetabolism did not contribute to podocyte injury. Similarly, we demonstrated that the decreased autophagic flux we observed in OSBPL7-deficient podocytes was not the mechanistic link between OSBPL7 deficiency and apoptosis. In a complementary zebrafish model, osbpl7 knockdown was sufficient to induce proteinuria and morphological damage to the glomerulus, underscoring its physiological relevance. Our study sheds new light on the mechanistic link between OSBPL7 deficiency and podocyte injury in glomerular diseases associated with CKD, and it strengthens the role of OSBPL7 as a novel therapeutic target.NEW & NOTEWORTHY OSBPL7 and ER stress comprise a central mechanism in glomerular injury. This study highlights a crucial link between OSBPL7 deficiency and ER stress in CKD. OSBPL7 deficiency causes ER stress, leading to podocyte apoptosis. There is a selective effect on lipid homeostasis in that OSBPL7 deficiency affects lipid homeostasis, altering cellular triglyceride but not cholesterol content. The interaction of ER stress and apoptosis supports that ER stress, not reduced autophagy, is the main driver of apoptosis in OSBPL7-deficient podocytes.

Vanillin, ferulic acid and their 1:1 combination inhibit lipid accumulation in 3T3 L1 adipocytes and 3D spheroids

BackgroundObesity is poised to be a major healthcare crisis worldwide. Genetic predisposition, inadequate activity, changing lifestyle and dietary patterns are cited as major causes for obesity. Even as a number of anti-obesity medications hit the market, there is still an ongoing quest to explore natural compounds, which are perceived as safer alternatives, for their anti-obesity activity. This study explores the anti-obesity potential of dietary polyphenols vanillin, ferulic acid and their combination using 3T3 L1 adipocytes and their 3D spheroids. MethodsStudies were conducted on differentiated 3T3 L1 adipocytes and their 3D spheroids. Assays conducted on 3T3 L1 adipocytes include Oil red O, fluorescent Nile Red staining and triglyceride quantification to assess effect on lipid droplet accumulation. 2 NBDG was used to assess glucose uptake following drug treatment. 3D spheroid cultures were generated and triglyceride content was quantified. Effect of drug treatment on gene expression was analysed using qRT-PCR. Results of monolayer culture were compared with 3D spheroid models. ResultsVanillin, ferulic acid and their combination lower intracellular triglyceride content and lipid droplet accumulation, inhibiting glucose uptake and conversion to triglycerides in 3T3 L1 adipocytes and their 3D spheroids. Compounds and their combination downregulated mRNA expression of C/EBP α and PPAR ɣ, FAS, ACC1, GLUT4, LPL, aP2. Vanillin treatment upregulated leptin mRNA expression. ConclusionVanillin, ferulic acid and their combination lower lipid accumulation and glucose uptake in 3T3 L1 adipocytes and 3D spheroids.

Nephroprotective Effect of Ferula assa-foetida Oleo Gum Resin on Type 2 Diabetic Rats.

Diabetic nephropathy is one of the main causes of kidney failure in the end stage of diabetes worldwide. On the other hand, asafoetida is a gum whose hypoglycemic effects have been proven. The present study was conducted with the aim of using asafoetida to prevent diabetic nephropathy. Diabetes was induced by a high-fat diet (60%) and streptozotocin injection (35 mg/kg) in rats. Diabetic rats were treated with an oral dose of 50 mg/kg of asafoetida for 8 weeks. At the end of the experiment, serum and urine parameters were examined. Antioxidant enzymes and lipid peroxidation levels in the kidney were also determined along with its histological examination. The expression levels of tumor necrosis factor-alpha and Transforming growth factor beta genes were also evaluated. Glucose, cholesterol, triglyceride, and HbA1c concentrations were significantly reduced in the asafoetida 50. On the other hand, in the treatment group, serum creatinine, urea, and albumin levels decreased and increased in urine. Antioxidant enzymes in the kidney improved significantly, and the expression of tumour necrosis factor-alpha and transforming growth factor-beta genes decreased. Histopathological examination also showed that necrosis, epithelial damage, and leukocyte infiltration increased in the diabetic and decreased in the treatment group. The result of biochemical analysis, enzymatic, and histological examinations showed that asafoetida may delay the progression of diabetic nephropathy due to the presence of anti-inflammatory and antioxidant activities.

Ameliorative effects of Monascus-fermented hawthorn extract on a high-fat diet-induced rat model of non-alcoholic fatty liver disease

ObjectiveThe aim of this study was to elucidate the effects of fermented hawthorn extract on high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats, and explore the possible underlying mechanisms. MethodsA total of 42 male adult Sprague-Dawley rats were randomly divided into five groups: normal control group (given a normal feed diet and distilled water by gavage), NAFLD model (given HFD and distilled water by gavage), low-, medium-, and high-dose fermented hawthorn extract treatment groups (given HFD and different doses of fermented hawthorn extract by gavage). After 12 weeks of gavage administration, changes in body weight, liver/body weight ratio, serum liver enzymes, as well as triglyceride (TG) content and oxidative stress levels in rat liver tissueswere detected. Histological evaluation was performed to observe the degree of fat accumulation (steatosis). qRT-PCR and western blotting were performed to detect the mRNA and protein expression of cytochrome P4502E1 (CYP2E1, a key enzyme associated with lipid peroxidation), and lipogenic factors (sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS)) in rat liver tissues. ResultsFermented hawthorn extract significantly reduced the body weight, decreased the levels of liver enzymes, improved hepatic steatosis, and exhibited obvious antioxidant effects. Fermented hawthorn extract also significantly down-regulated the mRNA and protein expression levels of CYP2E1, SREBP-1c and FAS. ConclusionOur findings suggested that fermented hawthorn extract can markedly reduce body weight, ameliorate HFD-induced NAFLD in rats, and exhibits significant antioxidant effects. Its underlying mechanism may depend on the inhibition of CYP2E1, SREBP-1c, and FAS expression.

Repeated marine heatwaves aggravate the adverse effects of nano-TiO2 on physiological metabolism of the thick-shelled mussel Mytilus coruscus

Global climate change is a major trigger of unexpected temperature fluctuations. The impacts of marine heatwaves (MHWs) and nano-titanium dioxide (nano-TiO2) on marine organisms have been extensively investigated. However, the potential mechanisms underlying their interactive effects on physiological processes and metabolism remain poorly understood, especially regarding periodic MHWs in real-world conditions. In this study, the effects of nano-TiO2 (at concentrations of 0, 25, and 250 μg/L) and periodic MHWs on the condition index (CI) and underlying metabolic mechanisms were investigated in mussels (Mytilus coruscus). The results showed that mussels try to upregulate their respiration rate (RR) to enhance aerobic metabolism (indicated by elevated succinate dehydrogenase) under short-term nano-TiO2 exposure. However, even at ambient concentration (25 μg/L), prolonged nano-TiO2 exposure inhibited ingestion ability (decreased clearance rate) and glycolysis (inhibited pyruvate kinase, hexokinase, and phosphofructokinase activities), which led to an insufficient energy supply (decreased triglyceride, albumin, and ATP contents). Repeated thermal scenarios caused more severe physiological damage, demonstrating that mussels are fragile to periodic MHWs. MHWs decreased the zeta potential of the nano-TiO2 particles but increased the hydrodynamic diameter. Additionally, exposure to nano-TiO2 and periodic MHWs further affected aerobic respiration (inhibited lactate dehydrogenase and succinate dehydrogenase activities), metabolism (decreased RR, activities of respiratory metabolism-related enzymes, and expressions of PEPCK, PPARγ, and ACO), and overall health condition (decreased ATP and CI). These findings indicate that the combined stress of these two stressors exerts more detrimental impact on the physiological performance and energy metabolism of mussels, and periodic MHWs exacerbate the toxicological effects of ambient concentration nano-TiO2. Given the potential worsening of nanoparticle pollution and the increase in extreme heat events in the future, the well-being of mussels in the marine environment may face further threats.

Studies on the characteristics of polycyclic aromatic hydrocarbons accumulation in lipids and the disturbance of lipid metabolism of Ruditapes philippinarum

Polycyclic aromatic hydrocarbons (PAHs) constitute a class of persistent organic pollutants with strong lipophilicity, which readily accumulate within organisms and have the effect to induce disorders in lipid metabolism. The present study aimed to investigate the accumulation localization and pattern of PAHs in Ruditapes philippinarum, and to reveal the association between PAHs and lipids metabolism. The 21-day exposure experiment was conducted using a mixture of phenanthrene, chrysene, and benzo[a]pyrene (the proportion is 1:1:1) at concentrations of 0.4 μg/L, 2 μg/L, and 10 μg/L. The tissue distribution of PAHs indicated that the digestive gland was the primary site of PAHs accumulation. Meanwhile, fluorescence colocalization suggested that PAHs primarily accumulated within the lipid droplets of digestive gland cells. This study further determined the transcriptomic and lipidomic profiles of the digestive gland to analyze the key genes involved in disrupted lipid metabolism and the major lipids affected. Lipidomic analysis identified the key differential metabolites as triglycerides (TGs). Furthermore, TGs were upregulated in the digestive gland had a total carbon atom number of 50–64 and a total number of 3–9 double bonds in the acyl side chains. Biochemical analysis experiments and oil red O stained frozen sections confirmed that the content of TGs steadily increased in various tissues during the experiment, leading to an elevated digestive gland index. Changes of lipid metabolism associated genes expression level also indicated that the synthesis of lipid in digestive gland were up-regulated while the decomposition was down-regulated. This study is the first to demonstrate the cellular localization of PAHs accumulation in bivalves and confirms the pattern of variation in TGs, providing new insights into the mechanisms of PAHs bioaccumulation and lipid metabolism disruption.

Abstract MP28: Advanced Lipid Status Parameters in Women With Preeclampsia

Preeclampsia (PE) is a hypertensive disorder associated with pregnancy, usually occurring after the 20th week of gestation, followed by proteinuria or signs of end-organ dysfunction. Early-onset preeclampsia is associated with placental dysfunction, while late-onset preeclampsia is recognized as a maternal disorder, influenced by risk factors like maternal obesity, diabetes mellitus, or chronic hypertension. During physiological pregnancy, lipid metabolism changes to adequately supply the fetoplacental unit with nutrients and energy, consequently changing the composition of LDL and HDL particles. However, in preeclampsia, these changes become atherogenic. The study aimed to examine changes in advanced lipid status parameter concentrations and the dominant diameter of LDL and HDL particles during pregnancies affected by PE. In this study, 92 pregnant women at high risk for complication development were followed longitudinally throughout the first (T1), second (T2), and third (T3) trimesters. They were classified into high-risk (HR) (72 women) and PE (20 women) groups based on pregnancy outcomes. Total cholesterol (TC), HDL-C, triglycerides (TG), apoAI, and apoB concentrations were measured using commercial kits, while LDL-C concentrations and the atherogenic index of plasma (AIP) were calculated using established equations. Dominant LDL and HDL particle sizes were determined by gradient gel electrophoresis. TG levels were significantly higher in the PE group compared to the HR group across all trimesters (p<0.05; p<0.05; p<0.01), while AIP was significantly elevated in T2 (p<0.01) and T3 (p<0.01). HDL-C levels were lower in the PE group than in the HR group in T2 (p<0.05). In the HR group during pregnancy, concentrations of TC, TG, LDL-C, apoB, as well as HDL-C increased significantly (p<0.05 for all parameters), while the dominant LDL diameter decreased markedly (p<0.001) between all trimesters, without changes in the dominant HDL diameter. There were no changes in HDL-C concentration during pregnancy in the PE group. In contrast, TG concentrations increased significantly (p<0.01), accompanied by a significant decrease in dominant LDL particle diameter (p<0.05). In conclusion, pregnant women with PE exhibit atherogenic changes in lipid status parameters, including no increase in HDL-C concentration, potentially leading to a loss of HDL's protective effect.

Insights into lipid function for ovarian development in the swimming crab (Portunus trituberculatus): A comparison of lipid mobilization and deposition in hepatopancreas and ovary

Ovarian development is a complex and dynamical process regulated by the coordinated actions of the hepatopancreas and ovary. In mammals, lipids provide necessary energy for oocytes to mature, whereas their regulatory role in crustaceans is not fully understood. This study compares lipid mobilization and deposition in hepatopancreas and ovary of the swimming crab at different stages of ovarian maturation. The results revealed that cholesterol (CHO) and triglyceride (TG) content in hepatopancreas increased with ovary development increased from stage I to Ⅲ, and then decreased at stage V, while those content in ovary significantly increased from stage I to V. Additionally, apolipoprotein (ApoA and ApoB) contents in hepatopancreas and ovary increased significantly during ovary development. Moreover, the highest expression levels of cholesterol transport related genes (srb, ldlr, lrp2 and abcg1) were observed in the hepatopancreas at stage Ⅲ and in the ovary at stage Ⅳ. Furthermore, as ovary development form stage I to Ⅳ, the hepatopancreas up-regulated the expression levels of genes related to lipid anabolism (fas, acc, g6pd, and 6pgd) and fatty acid transport (fabp9 and fatp4). Concurrently, genes related to lipid catabolism (il) and fatty acid β-oxidation (acox2 and acox3) in the hepatopancreas were down-regulated. Differently, with the ovary development increased from stage I to Ⅳ, the ovary up-regulated gene expression levels involved in lipid anabolism (acc, 6pgd, g6pd, dgat1, and gpat3), fatty acid synthesis (elovl and elovl4) and fatty acid β-oxidation (cpt1, cpt2, acox1, and acox3). The mRNA expression levels of lipolysis (tgl) and fatty acid transport (fabp1, fbap9, and fatp4) in ovary were down-regulated. Overall, these findings demonstrate that the hepatopancreas and ovary exhibit different responses to lipid metabolism during ovarian development.

Impact of Phenylketonuria on the Serum Metabolome and Plasma Lipidome: A Study in Early-Treated Patients.

Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann-Whitney U test, p < 0.05) analyses. Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated. This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason.

Psychosis metabolic risk calculator (PsyMetRiC) in early psychosis: External validation study in Finland.

Accurate detection of cardiometabolic risk in early psychosis is crucial to reducing somatic morbidity and mortality in people with psychotic disorders. We conducted an external validation of the psychosis metabolic risk calculator (PsyMetRiC), a cardiometabolic risk prediction tool developed in the UK and tailored for young people with psychosis. We compared the predictive accuracy and clinical usefulness of PsyMetRiC and a general population-based risk prediction tool for type 2 diabetes, the Finnish Diabetes Risk Score (FINDRISC). We included first-episode psychosis and ultra-high-risk for psychosis patients without metabolic syndrome aged 18-35 years from the Helsinki Early Psychosis and Turku Early Psychosis Study cohorts. We tested two versions of PsyMetRiC: the full model including age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations, and the partial-model excluding biochemical predictors, and the simplified FINDRISC including BMI, sex, systolic blood pressure, and fasting glucose. Discrimination, calibration, and decision curve analyses were used to assess the predictive performance and clinical usefulness of both PsyMetRiC and FINDRISC. We performed a site-specific re-calibration of PsyMetRiC (PsyMetRiC-Fi). The study sample consisted of 278 individuals (all White European ethnicity, 58.6% male, mean age 24.8 years, 37.8% smoking, mean BMI 23.5). Discrimination was marginally better in the PsyMetRiC full model (C = 0.72, 95% CI, 0.59-0.82) compared with partial model (C = 0.70, 95% CI 0.59-0.80) or FINDRISC (C = 0.63, 95% CI 0.54-0.71). Calibration plots displayed evidence of minor miscalibration for PsyMetRiC, which corrected following recalibration. Miscalibration was more pronounced for FINDRISC. Decision curve analysis showed that PsyMetRiC offers likely clinical usefulness in improving cardiometabolic risk management in early psychosis compared with giving everyone or no one an intervention. PsyMetRiC has utility in predicting cardiometabolic risk in Finnish patients with early psychosis. It has better discriminatory accuracy and offers more accurate risk prediction compared to other available strategies.

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.

Valine biased glycogen consumption to promote energy metabolism of Portunus trituberculatus and increased protein and essential amino acid deposition in muscle

The present research assessed the impact of dietary valine on nutritional and energy metabolism, as well as muscle development in swimming crabs (Portunus trituberculatus) over a period of six weeks. Swimming crabs, initially weighing around 23.34 ± 0.03 g, were given six diets identical in nitrogen and lipid levels (45 % and 8 % respectively). These diets contained valine contents of 0.99 %, 1.24 %, 1.56 %, 1.69 %, 1.90 %, and 2.20 % respectively. One hundred and eighty crabs were randomized into six treatments, each treatment including three replicates. The results suggested that significant increases were discovered in FW, PWG, as well as SGR of crabs when dietary valine increasing from 0.99 % to 1.69 %, but these measurements decreased when dietary valine increased to 2.20 %. Compare to the control treatment, crabs that were given diets with 1.90 % and 2.20 % valine showed increased level of muscle protein. Crabs that were given the diets containing 1.56 % and 1.69 % valine showed significantly increased concentration of GLU in hemolymph compared to the control group. Additionally, crabs that were given the diets containing 1.69 % valine and 1.90 % valine respectively showed significantly increased concentrations of T-CHO and TG in hepatopancreas. Hepatic glycogen concentration significantly decreased as the level of valine in diets increased from 0.99 % to 1.56 %, but significantly increased as valine level further increased to 2.20 %. Compared with the control group, crabs that were given diets with 1.90 % valine showed increased expression levels of genes associated to amino acid metabolism (pi3k, akt, alt, ast, 4ebp1 and eif4e3) and energy metabolism (pk, cs1, idh, nd1, cytb and cox2). Crabs given diets containing 2.20 % valine showed significantly increased expression level of pepck in hepatopancreas, while crabs given diets containing 1.24 %, 1.56 %, and 1.69 % valine exhibited significantly increased expression level of cpt1 in hepatopancreas. Crabs given the diet with 1.69 % valine had the highest expression levels of tor and pax7 in muscle. Increased dietary valine significantly reduced myofiber density but promoted higher frequency of myofibers in larger diameters. In conclusion, the optimal valine requirement for P. trituberculatus was 1.56 % of diet based on PWG by a quadratic modeling. 1.69–1.90 % valine promoted amino acid metabolism and muscle growth, moreover, enhanced energy metabolism by driving the consumption of glycogen rather than lipids.

Laminaria japonica Polysaccharide Regulates Fatty Hepatosis Through Bile Acids and Gut Microbiota in Diabetes Rat.

In this study, we examined the effect of Laminaria japonica polysaccharide (fucoidan) on the regulation of lipid metabolism. A rat model of diabetes mellitus (DM) was established by a high-sugar and high-fat diet combined with streptozotocin. Changes in the rats' body weight and blood glucose level during the experiment were recorded. Before the end of the experiment, an automatic biochemical analyzer was used to detect the fasting blood glucose (FBG), lipid content in serum, and insulin content, and calculate the insulin resistance index. Oil red O staining was used to detect lipid deposition in the liver. H&E staining, Masson staining, and PASM staining were used to observe the pathological structural changes in the liver. 16s RNA sequencing and targeted metabolomics were used to detect intestinal microbiota and bile acid content. The results showed that fucoidan was able to inhibit weight loss in the DM rats and reduce the content of triglycerides (TG), cholesterol (TC), and low-density lipoprotein (LDL-C) in serum. Oil red O staining showed a decrease in liver fat accumulation after fucoidan treatment. 16s RNA sequencing demonstrated that fucoidan increased the abundance of Bacteroidia, Campylobacteria, Clostridia, Gammaproteobacteria, Negativicutes, and Verrucomicrobi. Fucoidan also increased the secretion of secondary bile acids (Nor-DCA, TLCA, β-UDCA) and alleviated lipid metabolism disorders. The expression of α-SMA was inhibited by fucoidan, whereas the expression of FXR and TGR5 was promoted. Fucoidan shows good activity in regulating lipid metabolism by regulating the expression of FXR and TGR5 and acting on the intestinal flora-bile acid axis.

Influence of synergistic/competitive interactions of nonionic emulsifiers and proteins on the foam stability of whole egg liquids: Based on air-water and oil-water dual interface perspectives

Nonionic emulsifiers (NE) are widely used in sponge cakes because they can effectively improve the foaming properties of whole egg liquids (WEL). The WEL are rich in protein, lipids and water, forming air-water and oil-water interface during whipping and foaming. However, different NE plays different roles in the interface. No systematic study has been conducted on the stabilization mechanism of WEL by NE. This study first investigated the effect of different NE on the foaming properties of WEL. It was found that WEL with sucrose ester-9 (SE-9) had the highest foam stability (FS) (92.52%), while that with Tween 80 had the lowest (75.55%). It was found that this was related to the higher interfacial protein substitution ability of Tween 80. Next, free triglyceride content and CLSM analysis confirmed that NE promoted the formation of more oil-water interfaces in the foam. Moreover, NE could improve FS by reducing droplet size and increasing viscosity. Finally, the higher surface activity of NE than proteins was demonstrated by interfacial adsorption kinetics and dilatation rheology. SE-9 interacted with proteins at the air-water interface to enhance interfacial rigidity, whereas adsorption of Tween 80 led to a decrease in the rearrangement rate. The results also showed that the formation of oil-water interfacial films was dominated by the adsorption of NE. This study illustrated how different NE stabilized air-water and oil-water interfaces, and the effect of synergistic/competitive interactions with proteins on the stability of the interfaces. This will provide new insights into the stability regulation of WEL foam.

GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency.

Disruptions in circadian rhythms are associated with an increased risk of developing metabolic diseases. General control nonderepressible 2 (GCN2), a primary sensor of amino acid insufficiency and activator of the integrated stress response (ISR), has emerged as a conserved regulator of the circadian clock in multiple organisms. The objective of this study was to examine diurnal patterns in hepatic ISR activation in the liver and whole body rhythms in metabolism. We hypothesized that GCN2 activation cues hepatic ISR signaling over a natural 24-h feeding-fasting cycle. To address our objective, wild-type (WT) and whole body Gcn2 knockout (GCN2 KO) mice were housed in metabolic cages and provided free access to either a control or leucine-devoid diet (LeuD) for 8 days in total darkness. On the last day, blood and livers were collected at CT3 (CT = circadian time) and CT15. In livers of WT mice, GCN2 phosphorylation followed a diurnal pattern that was guided by intracellular branched-chain amino acid concentrations (r2 = 0.93). Feeding LeuD to WT mice increased hepatic ISR activation at CT15 only. Diurnal oscillations in hepatic ISR signaling, the hepatic transcriptome including lipid metabolic genes, and triglyceride concentrations were substantially reduced or absent in GCN2 KO mice. Furthermore, mice lacking GCN2 were unable to maintain circadian rhythms in whole body energy expenditure, respiratory exchange ratio, and physical activity when fed LeuD. In conclusion, GCN2 activation functions to maintain diurnal ISR activation in the liver and has a vital role in the mechanisms by which nutrient stress affects whole body metabolism.NEW & NOTEWORTHY This work reveals that the eIF2 kinase GCN2 functions to support diurnal patterns in the hepatic integrated stress response during natural feeding and is necessary to maintain circadian rhythms in energy expenditure, respiratory exchange ratio, and physical activity during amino acid stress.

Mechanism of fatty acid transposase (CD36) promoting fat accumulation in mule ducks

Mule ducks accumulate a large amount of fat in their livers when fed high-energy feed, which is predominantly used for producing fatty livers. Nevertheless, there is limited research on the molecular mechanisms underlying the formation of fatty liver in mule ducks. Fatty acid translocase (CD36) is a sensor for fatty acids and lipid metabolism regulator, which may play a crucial role in the accumulation of fat in the liver of mule ducks. In this study, Overexpression and CD36 gene interference for 24 h was followed by induction of liver cells with 400 µmol/L palmitic acid (PA) for 24 h. The results demonstrated that CD36 overexpression increased hepatic triglyceride content, lipid droplet deposition, oxidative stress, and cell apoptosis. However, interference with CD36 had the opposite effect. CD36 overexpression suppressed the expression of AMPK and CPT-1A genes but enhanced the expression of ACC1 and LKB1 genes, with interference yielding contrasting results. Additionally, the expression of CD36 inhibited the AMPK pathway, reduced AMPK phosphorylation, downregulated AMPK protein expression, and upregulated SREBP1 protein expression.This promoted palmitic acid-induced hepatocyte fat accumulation. In summary, CD36 promotes palmitic acid-induced fat accumulation in primary mule duck liver cells through the AMPK signaling pathway.

Ninerafaxstat in the Treatment of Diabetic Cardiomyopathy and Nonobstructive Hypertrophic Cardiomyopathy.

Ninerafaxstat is a novel mitotrope under investigation in 2 large clinical trials: IMPROVE-DiCE (a phase IIa trial investigating ninerafaxstat) and IMPROVE-hypertrophic cardiomyopathy (HCM). IMPROVE-DiCE is a single-center, open-label, phase 2a trial investigating the effectiveness of ninerafaxstat in diabetic cardiomyopathy. Ninerafaxstat significantly improved phosphocreatine/adenosine triphosphate median by 32% (P < 0.01) and reduced myocardial triglyceride content by 34% (P = 0.026). Magnetic resonance imaging (MRI) analysis showed improved left ventricular peak circumferential diastolic strain rate by 15% (P < 0.047) and peak left ventricular filling rate by 11% (P < 0.05). Pyruvate dehydrogenase flux was increased in 7 of 9 patients (P = 0.08), consistent with improved glucose utilization. IMPROVE-HCM (ninerafaxstat safe, effective for nonobstructive hypertrophic cardiomyopathy patients) is a phase 2, multicenter, randomized controlled and double-blinded study. From baseline to 12 weeks, ninerafaxstat was associated with a significantly improved ventilatory efficiency slope compared with placebo (P = 0.006). In a post hoc analysis with 35 patients with baseline Kansas City Cardiomyopathy Questionnaire score ≤80, changes in ventilatory efficiency slope favored ninerafaxstat versus placebo (P = 0.02). Left atrial size, a surrogate marker of diastolic dysfunction, was significantly decreased in patients on ninerafaxstat versus placebo (P = 0.01). These findings support a larger phase 3 study in symptomatic nonobstructive HCM patients to further investigate ninerafaxstat. Several drugs that also improve glucose utilization including fatty acid oxidation inhibitors, carnitine palmitoyltransferase I inhibitors, and glucagon-like peptide-1 receptor agonists are presently under investigation in clinical trials.

Alteration of growth performance, glycolipid metabolism, and bone characteristics of broiler chickens in response to different inclusion levels of dietary wheat.

The aim of this study was to evaluate the effects of different levels of wheat inclusion on growth performance, glycolipid metabolism, and tibial properties of broiler chickens. A total of 480 1-d-old male broiler chickens were initially fed identical starter diets until d 10. Subsequently, they were divided into 3 treatments consisting of 8 replicates with 20 birds per replicate, i.e., 1) low-level wheat addition group, with wheat ratios of 15% and 25% during the grower and finisher periods, respectively; 2) medium-level wheat inclusion group, incorporating 30% and 40% wheat in the grower and finisher diets, respectively; and 3) high-level wheat addition group, containing 55.8% and 62.4% wheat in the grower and finisher diets, until d 39. When compared to the low- and medium-level wheat diet, the high-level wheat inclusion in the diet increased feed intake and reduced the feed conversion ratio (both p<0.01), which was accompanied by a longer jejunum (p=0.031). Meanwhile, the high-level addition of wheat displayed a decreased abundance of Ruminococcin, Bacteroidetes, and Lactobacillus than the low-wheat group. With the increase of the proportion of wheat treatment, the contents of cholesterol, triglyceride, and high-density lipoprotein cholesterol were elevated in serum, whereas the concentration of serum C-terminal cross-linked telopeptide of type I collagen, a bone resorption marker, was decreased. In addition, the diet with medium and high levels of wheat improved the yield load of tibia, along with comparable bone dimension and weight. The medium- and high-level wheat additions increased serum glycolipid deposition and enhanced tibial mechanical properties, whereas the high-level wheat diet compromised the growth performance of broiler chickens, which might be associated with the alteration of gut microbiota.

Effects of Soybean Isoflavones on the Growth Performance and Lipid Metabolism of the Juvenile Chinese Mitten Crab Eriocheir sinensis

In order to study the effects of soybean isoflavones on the growth performance and lipid metabolism of juvenile Chinese mitten crabs, six experimental diets were formulated by gradient supplementation with 0%, 0.004% and 0.008% soybean isoflavones at different dietary lipid levels (10% and 15%). The groups were named as follows: NF-0 group (10% fat and 0% SIFs), NF-0.004 group (10% fat and 0.004% SIFs), NF-0.008 group (10% fat and 0.008% SIFs), HF-0 group (15% fat and 0% SIFs), HF-0.004 group (15% fat and 0.004% SIFs) and HF-0.008 group (15% fat and 0.008% SIFs). All crabs with an initial weight of 0.4 ± 0.03 g were fed for 8 weeks. The results showed that dietary supplementation with 0.004% or 0.008% SIFs significantly increased the weight gain and specific growth rate of crabs. Diets supplemented with 0.004% or 0.008% SIFs significantly reduced the content of non-esterified free fatty acids and triglycerides in the hepatopancreas of crabs at the 10% dietary lipid level. Dietary SIFs significantly decreased the relative mRNA expressions of elongase of very-long-chain fatty acids 6 (elovl6), triglyceride lipase (tgl), sterol regulatory element-binding protein 1 (srebp-1), carnitine palmitoyltransferase-1a (cpt-1a), fatty acid transporter protein 4 (fatp4), carnitine palmitoyltransferase-2 (cpt-2), Δ9 fatty acyl desaturase (Δ9 fad), carnitine palmitoyltransferase-1b (cpt-1b), fatty acid-binding protein 10 (fabp10) and microsomal triglyceride transfer protein (mttp) in the hepatopancreas of crabs. At the 15% dietary lipid level, 0.008% SIFs significantly increased the relative mRNA expressions of fatty acid-binding protein 3 (fabp3), carnitine acetyltransferase (caat), fatp4, fabp10, tgl, cpt-1a, cpt-1b and cpt-2 and significantly down-regulated the relative mRNA expressions of Δ9 fad and srebp-1. In conclusion, SIFs can improve the growth and utilization of a high-fat diet by inhibiting genes related to lipid synthesis and promoting lipid decomposition in juvenile Chinese mitten crabs.

Inhibitory Effect and Mechanism of Epigallocatechin Gallate on the Differentiation of 3T3-L1 Preadipocytes.

Green tea possesses a range of beneficial effects, including anti-obesity, antioxidant, and anti-inflammatory properties, owing to its biologically active components, primarily catechins such as epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG). However, few studies have investigated the four catechin monomers simultaneously, and the molecular mechanisms of their anti-obesity effects have not been fully elucidated. In this study, we investigated the effects of four catechin monomers on the differentiation of 3T3-L1 preadipocytes of mice. Our findings demonstrated that four catechin monomers EC/ECG/EGC/EGCG (12, 25, 50 µM) dose-dependently inhibited the differentiation of 3T3-L1 preadipocytes and reduced triglyceride content. EGCG exhibited the most potent inhibitory effect with an optimal concentration of 50 µM. In addition, transcriptome sequencing and lipidomic analysis of EGCG-treated 3T3-L1 preadipocytes revealed that Ptgs2 and Pim1 were the most differentially expressed genes involved in regulating adipocyte differentiation. The results suggested that EGCG up-regulated the expression of the Pla2g2e gene and down-regulated the expression of the Pla2g4a and Pla2g2a genes via the glycerophospholipid metabolic pathway, which subsequently elevated lysophosphatidylcholine (LPC) levels, influencing the differentiation process of 3T3-L1 preadipocytes.