Cell Lipid Research Articles

Preoperative neoadjuvant targeted therapy remodels intra-tumoral heterogeneity of clear-cell renal cell carcinoma and ferroptosis inhibition induces resistance progression

Neoadjuvant tyrosine kinase inhibitor (TKI) therapy is an important treatment option for advanced renal cell carcinoma (RCC). Many RCC patients may fail to respond or be resistant to TKI therapy. We aimed to explore the key mechanisms of neoadjuvant therapy résistance. We obtained tumor samples from matched pre-treatment biopsy and post-treatment surgical samples and performed single-cell RNA sequencing. Sunitinib-resistant ccRCC cell lines were established. Ferroptosis was detected by ferrous ion and lipid peroxidation levels. Tumor growth and resistance to Sunitinib was validated in vitro and vivo. Immunohistochemistry was used to validate the levels key genes and lipid peroxidation. Multi-center cohorts were included, including TCGA, ICGC, Checkmate-025 and IMmotion151 clinical trial. Survival analysis was performed to identify the associated clinical and genomic variables. Intratumoral heterogeneity was first described in the whole neoadjuvant management. The signature of endothelial cells was correlated with drug sensitivity and progression-free survival. Ferroptosis was shown to be the key biological program in malignant cell resistance. We observed tissue lipid peroxidation was negatively correlated with IL6 and tumor response. TKI-resistant cell line was established. SLC7A11 knockdown promoted cell growth and lipid peroxidation, increased the ferroptosis level, and suppressed the growth of tumor xenografts significantly (P < 0.01). IL6 could reverse the ferroptosis and malignant behavior caused by SLC7A11 (−) via JAK2/STAT3 pathway, which was rescued by the ferroptosis inducer Erastin. Our data indicate that ferroptosis is a novel strategy for advanced RCC treatment, which activated by IL6, providing a new idea for resistance to TKIs.

Individually Cultured Bovine Zygotes Successfully Develop to the Blastocyst Stage in an Extremely Confined Environment

The possibility of detecting the developmental competence of individually cultured embryos through analysis of spent media is a major current trend in an ART setting. However, individual embryo culture is detrimental compared with high-density group culture due to the reduced concentration of putative embryotropins. The main aim of this study was to identify an individual culture system that is not detrimental over high-density group culture in the bovine model. Blastocyst rates and competence were investigated in a conventional (GC) group, semi-confined group (MG), and individual culture (MS) in a commercial microwell device. Main findings showed that: (1) individual embryos can be continuously cultured for 7 days in ~70 nL microwells (MS) without detrimental effects compared with the GC and MG; (2) MS and MG blastocysts had a reduced number of TUNEL-positive cells compared to GC blastocysts; (3) though blastocyst mean cell numbers, mitochondrial activity, and lipid content were not different among the three culture conditions, MS blastocysts had a higher frequency of small-sized lipid droplets and a reduced mean droplet diameter compared with GC and MG blastocysts. Overall, findings open the way to optimize the development and competence of single embryos in an ART setting.

Exploring the Therapeutic Potential of β-Hydroxybutyrate (BHB) in Clear Cell Renal Cell Carcinoma: A Journey into Fat Browning, Autophagy, and Tumor Slimming

This study delves into the therapeutic potential of β-hydroxybutyrate (BHB) in clear cell renal cell carcinoma (ccRCC), a cancer known for its complex pathogenesis and resistance to conventional treatments. The research specifically explores the impact of BHB on cell viability, autophagy induction, and lipid metabolism in Caki-1 cells. The findings reveal that BHB significantly reduces ccRCC cell viability, particularly under low-glucose conditions. The combination of glucose and BHB treatment activates autophagy pathways, as evidenced by increased expression of autophagy-related genes (Beclin-1, LC3IIβ, and ATG5) and decreased expression of P62 after 48 and 72 hours. Moreover, the combined therapy enhances lipid metabolism, as indicated by elevated expression of PGC-1α and UCP-1, along with upregulation of ACSL3 and CPT1A, which are associated with lipid droplet formation and facilitate lipid breakdown within cells. The study concludes that BHB holds promise as a therapeutic agent for ccRCC, targeting abnormal lipid metabolism, inducing autophagy-mediated cell death, and promoting fat browning. The results suggest potential avenues for precision-guided nutritional therapies in ccRCC treatment, highlighting the innovative role of BHB in addressing the challenges posed by this cancer.

Effects of salinity on the growth, physiological and biochemical components of microalga Euchlorocystis marina

Euchlorocystis marina, a new marine species of the genus Euchlorocystis discovered in 2022, has the potential to improve the water quality in mariculture ponds. However, the effects of salinity on the growth, physiology, and biochemical composition of these algae are not well understood. In this study, changes in physiological and biochemical indices such as cell density, photosynthetic pigment, polysaccharide, and lipid content of E. marina under different salinity treatments were analyzed. The results showed that the highest cell density was observed at a salinity of 15‰. The lowest photosynthetic pigment content was observed at a salinity of 60‰, and the highest polysaccharide and lipid content was observed at a salinity of 60‰. These results indicated that lower salinity was more conducive to E. marina reproduction and growth. E. marina can accumulate polysaccharides and lipids in high salinity environments. This study provides new information for understanding the salinity adaptation strategies of E. marina and has practical significance for its development and utilization.

Effect of high sodium ion level on the interaction of AmB with a cholesterol-rich phospholipid monolayer.

Invasive fungal infections are a primary reason for high mortality in immunocompromised people, especially in critically ill patients, such as intensive care unit (ICU) patients, advanced cancer patients, or severe burn patients. Hypernatremia also can increase mortality in severely ill patients. Amphotericin B (AmB) is the gold standard for treating infections, but in severely ill patients, AmB can cause hematotoxicity when administered intravenously due to its interaction with cholesterol on red blood cell membranes. This results in limited doses of AmB and affects the treatment of infections. The proportion of cholesterol molecules in membrane lipids in red blood cells is as high as 50mol%, and the sodium ions can influence the interaction between AmB and lipids on the membrane. Therefore, in the complex clinical situation of a severely ill patient with a fungal infection and hypernatremia, the interaction between amphotericin B and the red blood cell membranes is worth studying in depth. In this work, the interaction between AmB and the dipalmitoyl phosphatidylcholine (DPPC)/cholesterol mixed monolayer in the presence of high sodium ion levels was studied when the proportion of cholesterol was 50%. The results show that the effect of AmB on reducing the monolayer's area at a high level of sodium ions is slightly stronger at 30mN/m. The effect of AmB on reducing the elastic modulus of the DPPC/Chol monolayer is significantly weakened by a high sodium ion level, compared with the level of sodium ions at normal physiological concentration. The higher the sodium ion concentration, the weaker the intermolecular force of the DPPC/Chol/AmB mixed monolayers. The scanning electron microscope (SEM) and atomic force microscopy (AFM) observations suggest that at a high sodium ion level, the presence of AmB significantly reduces the surface roughness of the DPPC/Chol monolayer. AmB may bind to cholesterol molecules, and it isolates cholesterol from the monolayer, resulting in a reduced height of the cholesterol-rich monolayer and an increasingly dispersed monolayer region. The results are beneficial to understanding the mechanism of impact of a high sodium ion level on the relationship between AmB and red blood cell membranes rich in cholesterol and are valuable for understanding the hemolytic toxicity of AmB to red blood cells at a high sodium ion level.

Review of salivary antioxidants and their barriers

Background: Oxidative stress results from the imbalance between reactive oxygen species (ROS) and cellular antioxidant defenses. Oxidative stress can cause damage to cellular structures such as cell membranes, lipids, proteins, lipoproteins, and deoxyribonucleic acids when free radicals are present in excess. Antioxidant mechanisms protect tissues against oxidative stress by decreasing free radical levels in cells through the inhibition of activities or expression of free radical-generating enzymes. Purpose: The purpose of this paper is to discuss the role of antioxidants in protecting cells from the harmful effects of ROS, particularly in the context of oral mucosa, and to clarify which molecules disrupt the pathway of these antioxidants. Review: Salivary peroxidase, catalase, superoxide dismutase, and glutathione reductase are enzymatic salivary antioxidants, and uric acid, reduced glutathione, albumin, and lactoferrin are non-enzymatic antioxidants. Both types of antioxidants regularly donate an electron to free radicals to reduce their levels in cells. Conclusion: Antioxidant activities may be disrupted by signaling mechanisms resulting from barrier regulations observed in tissue. The increased expression of malondialdehyde is an indicator of disrupted antioxidant barriers.

The effects of exposure to and timing of a choline-deficient diet during pregnancy and early postnatal life on the skeletal muscle transcriptome of the offspring

Nonalcoholic fatty liver disease (NAFLD) is related to muscle loss, but the precise mechanism underlying this association remains unclear. The aim of the present study was thus to determine the influence of maternal fatty liver and dietary choline deficiency during pregnancy and/or lactation periods on the skeletal muscle gene expression profile among 24-day-old male rat offspring. Histological examination of skeletal muscle tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global transcriptome pattern was assessed using a microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time PCR (qPCR). Morphological differences in fat accumulation in skeletal muscle related to choline supply were observed. The global gene expression profile was consistent with abnormal morphological changes. Mettl21c gene was overexpressed in all choline-deficient groups compared to the NN group, while two genes, Cdkn1a and S100a4, were downregulated. Processes of protein biosynthesis were upregulated, and processes related to cell proliferation and lipid metabolism were inhibited in DD, DN, and ND groups compared to the NN group. Prenatal and early postnatal exposure to fatty liver and dietary choline deficiency leads to changes in the transcriptome profile in skeletal muscle of 24-day old male rat offspring and is associated with muscle damage, but the mechanism of it seems to be different at different developmental stages of life. Adequate choline intake during pregnancy and lactation can prevent severe muscle disturbance in the progeny of females suffering from fatty liver.

Polysaccharide extracted from Sarcandra glabra residue attenuate cognitive impairment by regulating gut microbiota in diabetic mice

Diabetic encephalopathy (DE), characterized by cognitive impairment, currently lacks targeted treatment. Previous studies have shown that Sarcandra glabra extracted residue polysaccharide (SERP) exhibited hypoglycemic effects either in vitro or in streptozotocin-induced diabetes mice. However, the therapeutic effect of SERP on DE was not elucidated. This study investigated the therapeutic effect of SERP on DE and its underlying mechanism. Our results revealed that SERP regulates glucose and lipid metabolism, improves cognitive function, and exhibits diminished activity post-antibiotic intervention. Importantly, we discovered a novel mechanism by which SERP modulates the gut microbiota, specifically enriching Bacteroidales S24-7, resulting in elevated levels of butyric acid in the intestine. This regulation modulates the intestinal endocrine cell lipid metabolism level, restores damaged intestinal barriers and neural epithelial circuits, thus exhibiting cure effects. Our findings suggest that SERP could become a candidate for treating DE, potentially involving the regulation mechanism of the “microbiota-gut-brain axis”. This study underscores the unique therapeutic efficacy of SERP in managing DE, offering fresh drug candidates and innovative treatment strategies for this challenging condition.

Circ_WASF2 regulates ferroptosis by miR-634/ GPX4 signaling in pancreatic cancer

PurposePancreatic cancer (PC) is one of the most lethal malignant gastrointestinal tumors (GI) characterized by a poor prognosis. Ferroptosis is an emerging programmed cell death that plays an essential role in the progression of various cancers. Ferroptosis is driven by iron-dependent phospholipid peroxidation and is regulated by mitochondrial activity, lipid peroxidation, and reactive oxygen species (ROS). The function and mechanism of ferroptosis in PC need more research.MethodsThe levels of circRNAs, miRNAs, and mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used for protein detection. CCK8 assays were used to detect cell proliferation. Cell death, lipid peroxidation, ROS, and Fe2+ were detected by indicted kits. Dual-luciferase reporter and RNA pull-down assays were conducted to confirm the interaction between circRNAs, miRNAs, and mRNAs.ResultsIn this research, we found that circular RNA hsa_circ_0000003(circ_WASF2) was upregulated in pancreatic cancer cells. The silence of circ_WASF2 inhibited cancer proliferation and increased cell death by increasing ferroptosis accompanied by up-regulation of lipid peroxidation, ROS, and Fe2+. Further studies showed that circ_WASF2 could attenuate ferroptosis by targeting miR-634 and the downstream glutathione peroxidase 4 (GPX4). GPX4 has been well-reported as a central factor in ferroptosis. Our research revealed a new pathway for regulating ferroptosis in PC.ConclusionIn summary, we have determined that circ_WASF2/miR-634/GPX4 contributed to ferroptosis-induced cell death, and provided a possible therapeutic target in PC.

Resuspended freeze-dried Nannochloropsis as a model laboratory system for concentrated fresh Nannochloropsis in ultrasound cell disruption experiments

Microalgae have rigid, complex cell walls hindering direct lipid extraction. Cell disruption techniques are used to rupture these cellular structures to increase lipid extraction. Researchers investigating the downstream processing of microalgae do not always have access to microalgal cultivation systems to generate large amounts of fresh microalgal biomass. Using resuspended freeze-dried microalgal biomass as a model laboratory system for concentrated fresh biomass during cell disruption experiments offers greater flexibility in experimental planning and omits investment costs of microalgal cultivation equipment. So far, it however remains unclear whether freeze-dried resuspended biomass can be used as a model laboratory system to represent concentrated fresh biomass during cell disruption and lipid extraction experiments. This paper thus evaluated the suitability of resuspended freeze-dried Nannochloropsis as a model laboratory system for concentrated fresh Nannochloropsis during cell disruption. Ultrasound assisted cell disruption was used as example cell disruption technique and lipid extraction efficiency and free fatty acid content were investigated. Tap water and 3% sodium chloride are both suitable resuspension media for the resuspension of freeze-dried Nannochloropsis. Resuspension duration should be limited (&amp;lt; 120 min) to prevent the formation of free fatty acids. The condition of the biomass (concentrated fresh, or resuspended freeze-dried) prior to ultrasound assisted cell disruption did not influence the resulting lipid extraction efficiency. Resuspended freeze-dried Nannochloropsis biomass in tap water or 3% sodium chloride can thus be used as a model laboratory system for fresh microalgal biomass during research on ultrasound assisted lipid extraction. The generalization of the results to other cultivation conditions, cell disruption techniques, components of interest or microalgal species should be carefully assessed.

Production of lignin monomeric alcohols and lipids from oil palm empty fruit bunch by a combination of alkaline nitrobenzene depolymerization and Lipomyces starkeyi bioconversion

The efficient valorization of lignocellulosic biomass into valuable chemicals represents a cornerstone for advancing sustainable bioeconomy practices. This study focuses on the innovative conversion of oil palm empty fruit bunch (OPEFB) into lignin monomeric alcohols and lipids through a novel two-step process combining alkaline nitrobenzene depolymerization and bioconversion by Lipomyces starkeyi. Initially, OPEFB undergoes alkaline nitrobenzene depolymerization to break down complex lignin structures into monomeric aldehydes. The resulting derivates serve as substrates for the bioconversion by L. starkeyi, which is competent at metabolizing lignin-derived compounds into higher-value lignin monomeric alcohols (syringyl, vanillyl, and 4-hydroxybenzyl alcohol) and lipids, simultaneously. The strategy delineates the optimization of depolymerization conditions, sodium hydroxide concentration, nitrobenzene effect, and reaction time to maximize the yield of depolymerized lignin suitable for bioconversion. Subsequently, the bioconversion process toward cell growth, lipid production, and fatty acid profiles in various fermentations by L. starkeyi was explored. The highest syringaldehyde and vanillin obtained reached up to 4.81 mM and 0.64 mM, respectively. Then, it successfully produced 3.57 mM and 0.40 mM of syringyl alcohol and vanillyl alcohol, respectively, with 5.86 g L−1 of the lipid titer. The study demonstrates the potential of this integrated approach to convert OPEFB into valuable lignin-derived biochemicals and lipids, thereby contributing to the development of alternative strategies for biomass utilization efficiently.

Abstract PO3-05-09: The impact of body mass index on CDK4/6 inhibitor treatment survival outcomes in metastatic breast cancer

Abstract Introduction: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are important in the treatment of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). Previous studies have shown that CDK4/6is affect metabolic processes and cell metabolism, including adipogenesis, lipid synthesis, and glucose regulation. Obesity has been associated with worse survival in breast cancer. We aimed to assess the effect of body mass index (BMI) on survival outcomes in patients treated with CDK4/6is for MBC. Methods: Patients diagnosed with metastatic HR+/HER2-negative BC and who were treated with palbociclib, ribociclib, or abemaciclib from 6/10/2015 to 12/28/2022 were selected from the Montefiore Health system database and followed until 3/24/2023. The patients were divided into three groups according to BMI level as follows; normal: 18.5-24.9 kg/m2, overweight: 25-29.9 kg/m2 and obese: ≥ 30 kg/m2. Patients were also stratified by BMI measured after 3 months of therapy. Characteristics of the patients and tumors in the subgroups were compared using chi-squared/Fisher’s exact test for categorical data and Kruskal-Wallis/Wilcox signed rank tests for continuous data. Kaplan-Meier and Cox proportional hazards analysis were used to compare overall survival (OS) and progression free survival (PFS). Results: Among 221 patients, 66 were normal weight, 78 were overweight, and 77 were obese. There was no statistically significant difference in clinicopathological characteristics among the cohorts. Neither BMI measured at baseline nor after 3 months of therapy had any association with OS (P = 0.8 at baseline and P = 0.1 after 3 months) or PFS (P = 0.4 at baseline and P = 0.6 after 3 months). Multivariable analysis showed no statistically significant association between BMI and worse OS (HR: 1.1 for overweight, P = 0.7; and 0.96 for obese, P = 0.9) or worse PFS (HR: 0.9 for overweight, P = 0.8; and 0.76 for obese, P = 0.5). Multivariate analysis revealed a significant effect of obese BMI after 3 months of treatment on OS (HR: 0.48, P = 0.035) but not on PFS (HR: 0.88, P = 0.8). Overweight BMI after 3 months of treatment was not found to have a significant effect on OS (HR: 0.49, P = 0.063) or PFS (HR: 0.89, P = 0.9). Conclusion: The clinical effectiveness of CDK4/6is was not found to be influenced by BMI measured prior to therapy; however, there may be an association between improved OS and obese BMI after 3 months of treatment. Median OS and PFS in patients with MBC comparing different BMI groups (normal, overweight, and obese) at baseline prior to therapy and after 3 months of therapy. Table 1 Baseline characteristics of patients with MBC comparing different BMI groups (normal, overweight, and obese) at baseline prior to therapy and after 3 months of therapy. Table 2 Table 3 Multivariable analysis of OS and PFS for patients with MBC comparing different BMI groups (normal, overweight, and obese) at baseline prior to therapy and after 3 months of therapy. Citation Format: Frank Zhang, Jesus Anampa Mesias. The impact of body mass index on CDK4/6 inhibitor treatment survival outcomes in metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-09.

Evaluation of environmental parameters for optimal cell density, biomass, lipid, and biodiesel production in scenedesmus: Focus on suspension and biofilm methods

The study focused on investigating the impact of various environmental parameters on the production of Scenedesmus, a unicellular alga known for its industrial and food value. The parameters studied included production method, temperature, lighting period, light intensity, and pH, with a particular emphasis on suspension and biofilm production methods. The results highlighted optimal conditions for different aspects of production, such as cell density, biomass production, lipid production, and biodiesel production. Specifically, the findings indicated that the highest cell density was achieved at a temperature of 25 °C, light intensity of 3000 lux, lighting period of 16 h, and pH of 8. For biomass production, the optimal conditions were a temperature of 25 °C, light intensity of 3000 lux, lighting period of 18 h, and pH of 9. The greatest lipid production was observed at a temperature of 20 °C, light intensity of 4000 lux, lighting period of 18 h, and pH of 8. Moreover, the highest biodiesel production was recorded at a temperature of 25 °C, light intensity of 3000 lux, lighting period of 18 h, and pH of 8. Notably, the study found that the biofilm production method outperformed the suspension method across various parameters, including cell density, biomass production, lipid production, and biodiesel production. These results contribute to the existing knowledge of optimal conditions for microalgae production and underscore the potential of Scenedesmus in industrial and food applications.

Abstract 1005: Hypertriglyceridemia Promotes Aortic Aneurysm Formation And Rupture In Angiotensin Ii Infused Mice

Plasma total cholesterol (TC) and triglyceride (TG) are reported to be positively associated with the risk of abdominal aortic aneurysm (AAA). Our group discovered that hypercholesterolemia augments angiotensin II-induced AAA in mice. We also found that remnants of triglyceride-rich lipoproteins (TRLs) may be crucial for AngII-induced AAA. Recently, it was reported that hypertriglyceridemia (HTG) caused by inducible lipoprotein lipase deficiency (iLpl-/-) results in uptake and accumulation of TRL lipid in aortic endothelial cells in vivo. Based upon these findings, we hypothesized that HTG stimulates AAA formation. Methods: Adult male and female Lplf/f.beta-actin-Mer/Cre/Mer 1/0 and Lplf/f mice were administered 75 mg/kg/day tamoxifen for 5 consecutive days. Mice were fed either a standard diet (SD) throughout the study or a Western-type diet (WD) starting 1 wk after the completion of tamoxifen administration and continuing for a total of 5 wks. Mini osmotic pumps were implanted in mice 2 wks after completion of tamoxifen administration and delivered saline or AngII at 1,000 ng/kg/min for 4 wks. Results: AngII infused and SD fed iLpl-/- versus Lplf/f mice had elevated plasma TG and TC levels but similar abdominal aortic external diameter and AAA incidence. Since the SD was low in fat, a high fat WD was then fed to AngII-infused mice. Plasma TG and TC were increased in female iLpl-/- versus Lplf/f mice. However, plasma lipid concentrations could not be measured in male iLpl-/- because 10 of 11 animals had died from aortic rupture. In contrast, none of the male Lplf/f mice died and only 4 of 11 had abdominal aortic dilation. Female compared to male iLpl-/- mice were protected from AngII-induced aortic rupture (1/11 died) and only 1 of 9 females had abdominal aortic dilation. To eliminate the possibility that HTG alone caused aortic rupture in male mice, the study was repeated with the addition of saline infusion. In agreement with the first study, AngII plus WD lead to death by aortic rupture in all male iLpl-/- mice (9/9). In contrast, iLpl-/- male mice infused with saline had markedly greater survival (1/5 died of unknown cause). Conclusions: HTG causes aortic aneurysm development in AngII-infused male iLpl-/- mice. Thus, treating HTG could reduce AAA risk.

Maternal Exercise Improves Infant Mesenchymal Stem Cell Lipid Storage and Oxidation, and Decreases Infant Adiposity

Rates of pediatric obesity are continuously rising and are likely to translate into high incidence of metabolic disease later in life. Maternal exercise during pregnancy has been established as a useful non-pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to a multitude of infant peripheral tissue (e.g., skeletal muscle) and remain involved in mature tissue repair and maintenance. Importantly, these cells preserve the phenotype of an offspring donor and represent a model for the investigation of mechanisms behind infant metabolic health improvements. We used undifferentiated MSC collected during a randomized controlled trial to investigate if maternal exercise, regardless of exercise mode, affects infant adiposity and fatty acid oxidation. Compared to control, we observed &gt;160% higher neutral lipid content in Ex-MSCs (p&lt;0.01). However, this finding was coupled with significantly higher complete fatty acid oxidation to CO2 and lower incomplete fat oxidation (ASM production) in Ex-MSCs (p≤0.05). Infants in the exercise group had significantly lower body fat percentage compared to same age infants of controls at one month of age (p≤0.05). There was no difference in lean body mass volume (p&gt;0.05) or infant one-month BMI (p=0.069). Together, these data indicate that maternal exercise exposure in utero is still associated with decreased infant adiposity one month after birth. MSC lipid content was positively associated with maternal fitness and exercise volume (p&lt;0.01) during pregnancy. Finally, an increase in average maternal exercise volume (MET*min/wk; r=-0.4, p≤0.05) and total gestational MET*min (r=-0.36, p≤0.05), but not VO2max (p=0.07) was associated with infant 1-month body fat percentage. Together, these data showcase the influence of maternal exercise exposure on improvements in cellular metabolism and at 1 month of age. Collectively, our data suggests that exposure to maternal exercise could contribute to lower adiposity in early infancy. This project was supported by the American Heart Association (18IPA34150006 to L.E.M.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dual stress factors adaptive evolution for high EPA production in Schizochytrium sp. and metabolomics mechanism analysis.

Eicosapentaenoic acid (EPA) is a vital ɷ-3 polyunsaturated fatty acid (PUFA) for human body with various physiological functions. In this study, we proposed an adaptive evolutionary strategy based on high-temperature and high-oxygen two-factor stress to increase the EPA production capacity of Schizochytrium. High-temperature stress was used to increase EPA yield, and high oxygen was implemented to continuously stimulate cell growth and lipid accumulation. The biomass and EPA production of ALE-D50 reached 35.33g/L and 1.54g/L, which were 43.85% and 71.11% higher than that of the original strain, respectively. Lower in vivo reactive oxygen species levels indicated that the evolved strain possessed stronger antioxidant activity. Liquid chromatography-mass spectrometry metabolomics showed that enhanced glucose consumption and glycolysis metabolism, as well as a weakened tricarboxylic acid cycle and reduced amino acid metabolic tributaries in the evolved strain, might be associated with increased growth and EPA synthesis. Finally, the lipid production and EPA production in a fed-batch fermentation were further increased to 48.93g/L and 3.55g/L, improving by 54.30% and 90.86%, respectively. This study provides a novel pathway for promoting EPA biosynthesis in Schizochytrium.

Myo-inositol supplementation in obese patients with non-alcoholic fatty liver disease: Assessment of sirtuin-1 pathway, atherogenic and hematological parameters

BackgroundNon-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is closely associated with higher risks of atherosclerosis through a number of molecular cascades such as the sirtuin-1 (SIRT-1) pathway. Myo-inositol as a precursor isomer of cyclohexanehexols exerts anti-hyperlipidemic and anti-obesity features in metabolic disorders. The current study aimed to assess the effects of myo-inositol supplementation on genes expression of the SIRT-1 pathway, atherogenic indices, and hematological parameters in obese patients with NAFLD. MethodsThis double-blinded randomized clinical trial was conducted on 44 obese patients with ultrasound proven- NAFLD who received dietary recommendations and were randomly allocated into either myo-inositol (4 g/day) or placebo (maltodextrin 4 g/day) receiving groups for 8 weeks. At baseline and the end of the study mRNA expression levels of SIRT-1 pathway genes in peripheral blood mononuclear cells (PBMCs), complete blood cell count, lipid profile, and atherogenic indices were assessed. Inter-group differences were determined using analysis of covariance (by adjusting for the potential confounders) at the end of the trial. ResultsAt the end of the trial mRNA expression levels of low-density- lipoprotein receptor (LDLR) (only in myo-inositol group) and endothelial nitric oxide synthase (eNOS) (in both groups) significantly increased, compared with steady-state levels (p = 0.004 and p = 0.001, respectively). Moreover, myo-inositol supplementation significantly inhibited lectin-like oxidized- low-density lipoprotein receptor-1 (LOX-1) expression compared with the placebo group (p = 0.045). Slight improvements in Cholesterol-related atherogenic indices and hematological parameters were also observed in myo-inositol group, compared with baseline values (p < 0.05). ConclusionMyo-inositol supplementation could slightly activate SIRT-1 pathway and thereby exert marginal anti-atherosclerotic properties in obese patients with NAFLD.

Preliminary hazard assessment of a new nature-inspired antifouling (NIAF) agent

A recently synthesized aminated 3,4-dioxygenated xanthone (Xantifoul2) was found to have promising antifouling (AF) effects against the settlement of the macrofouler Mytilus galloprovincialis larvae. Preliminary assessment indicated that Xantifoul2 has reduced ecotoxicological impacts: e.g., being non-toxic to the marine crustacea Artemia salina (<10 % mortality at 50 μM) and showing low bioconcentration factor in marine organisms. In order to meet the EU Biocidal Product Regulation, a preliminary hazard assessment of this new nature-inspired antifouling (NIAF) agent was conducted in this work. Xantifoul2 did not affect the swimming ability of the planktonic crustacean Daphnia magna, the growth of the diatom Phaeodactylum tricornutum, and the cellular respiration of luminescent Gram-negative bacteria Vibrio fischeri, supporting the low toxicity towards several non-target marine species. Regarding human cytotoxicity, Xantifoul2 did not affect the cell viability of retinal human cells (hTERT-RPE-1) and lipidomic studies revealed depletion of lipids involved in cell death, membrane modeling, lipid storage, and oxidative stress only at a high concentration (10 μM). Accelerated degradation studies in water were conducted under simulated sunlight to allow the understanding of putative transformation products (TPs) that could be generated in the aquatic ecosystems. Both Xantifoul2 and photolytic-treated Xantifoul2 in the aqueous matrix were therefore evaluated on several nuclear receptors (NRs). The results of this preliminary hazard assessment of Xantifoul2, combined with the high degradation rates in water, provide strong evidence of the safety of this AF agent under the evaluated conditions, and provide the support for future validation studies before this compound can be introduced in the market.

Development of intestine-targeted microcapsules for enhanced delivery of fucoxanthin: A strategy to mitigate lipid accumulation in vitro and in vivo

The development of intestine-targeted microcapsules using spray drying without maltodextrin is still a challenge. Herein, intestine-targeted fucoxanthin-loaded microcapsules (Fx-MIC) were developed using the spray drying method. The microcapsules were formed by homogenizing fucoxanthin/conjugated linoleic acid (Fx/CLA) and whey protein isolate/Arabic gum (WPI/AG) mixture, followed by spray drying without maltodextrin. The effect of the ratio of Fx/CLA to WPI/AG in Fx-MIC on their morphology and encapsulation efficiency was evaluated. An Fx/CLA-to-WPI/AG ratio of 1:3 yielded a uniform particle size and the highest encapsulation efficiency (91.11%). In vitro simulated digestion demonstrated that Fx-MIC effectively protected Fx from premature release in the stomach and exhibited a release efficiency of 66.08% in the intestine. The digestion product of Fx-MIC effectively inhibited 3T3-L1 cell differentiation and lipid accumulation, demonstrating its ability to reduce lipid accumulation in vitro. Moreover, in high-fat diet (HFD)-induced obesity mice, Fx-MIC exhibited significant reductions in body weight, liver weight, and fat mass. Additionally, Fx-MIC demonstrated notable effects on lowering blood lipid levels and mitigating liver damage. In conclusion, the use of Fx-MIC facilitated the targeted release of Fx, thereby enhancing its anti-obesity effects. This promising result suggests potential applications of Fx-MIC in the food industry.

Elucidating the genetic aspect of yellow shoulder disorder in tomato (Solanum lycopersicum) by QTL-seq and linkage mapping

The color and color uniformity of the fruits are of paramount importance to fresh consumption and the tomato processing industry. This is mostly because consumers often associate vibrant and uniform colors with freshness and quality. Yellow shoulder disorder (YSD) characterized by discolored yellow or green sectors on fruit skin is one of the major concerns for tomato producers worldwide since YSD symptoms adversely affect market value and consumer appeal. Therefore, YSD has been studied for a long time, but the genetic aspect of the problem has not been a major focus and hence, it has remained mostly unknown. So, the objective of this research was to identify the genetic components of the YSD. An F2 mapping population was developed and phenotyped for the YSD Visual Score. The F2 plants showing extreme phenotypes were selected and bulks were created. After whole genome sequencing of these bulks, three Quantitative Trait Loci (QTL)s namely YSD1.1 on chromosome 1, YSD3.1 on chromosome 3, and YSD11.1 on chromosome 11 were identified using QTL-seq and traditional linkage mapping. These three QTLs explained approximately 20 % of the phenotypic variation in the F2 mapping population. Further, candidate genes in each QTL interval were identified based on their expression profile and genetic polymorphisms such as single nucleotide polymorphisms (SNPs) and insertions/deletions (INDELs) on genic/intergenic regions. These genes involve in fruit ripening, cell wall modification, lipid metabolism and starch degradation. The present study reports the first QTLs associated with YSD resistance and 17 KASP markers that can be used in marker-assisted selection for YSD in tomato.