Decrease In Lipid Content Research Articles

Influence of Varied Carbon Sources and Carbon-Nitrogen Ratio on Microbial Community in a Biofloc-Based Culture System and Their Effects on Growth Performance, Proximate Composition, Hematology and Oxidative Stress in Nile Tilapia

This study investigates the influence of varied carbon sources and carbon-nitrogen ratio on microbial community in a biofloc-based culture system and their effects on growth performance, proximate composition, hematology, and oxidative stress in Nile tilapia. The experiment involved three different carbon-nitrogen ratios (10:1, 15:1, 20:1) and two carbohydrate sources (molasses: ML-10, ML-15, ML-20, starch: S-10, S-15, and S-20) with three replicates each. A diet containing 25% crude protein was fed to fish in 18 experimental units for 120 days. Carbohydrate supplementation significantly increased the total heterotrophic bacterial (THB) count from C/N10 to C/N20 while decreasing pH, total ammonia nitrogen, and nitrate nitrogen contents. In addition, growth was considerably greater in the ML-10 and ML-15 groups compared to the C/N20 group. Increasing the C/N ratio increased body protein and ash, decreased lipid contents, and increased the activities of lysozyme, SOD, CAT, and GPx. Finally, the C/N10 and C/N15 groups showed significantly lower GLU and COR concentrations in biofloc compared to the C/N20 group. Furthermore, increasing the C/N ratio up to 15 resulted in improved outcomes in terms of Hb, WBCs, RBCs, and Ht content. Overall, the utilization of the C/N15 group resulted in suitable growth, proximate composition, and immunity in Nile tilapia.

Serpina3c Deficiency Promotes Obesity-related Hypertriglyceridemia and Inflammation through Activation of the Hif1α-glycolysis Axis in Adipose Tissue.

Adipose tissue dysfunction leads to abnormal lipid metabolism and high inflammation levels. This research aims to explore the role of Serpina3c, which is highly expressed in adipocytes, in obesity-related hypertriglyceridemia and metaflammation. Serpina3c global knockout (KO) mice, adipocyte-specific Serpina3c overexpressing mice, Serpina3c knockdown (KD) mice, and hypoxia-inducible factor 1 alpha(Hif1α) KD mice were fed a high-fat diet (HFD) for 16 weeks to generate obesity-related hypertriglyceridemia mice models. In the present study, Serpina3c KO mice and adipocyte-specific Serpina3c KD mice exhibited more severe obesity-related hypertriglyceridemia and metaflammation under HFD conditions. Serpina3c KO epididymal white adipose tissue (eWAT) primary stromal vascular fraction (SVF)-derived adipocytes exhibited higher lipid (triglyceride and non-esterified fatty acid) levels and higher fatty acid synthase expression after palmitic acid stimulation. Adipocyte-specific Serpina3c overexpression in KO mice prevented the KO group phenotype. The RNA-seq and in vitro validation revealed that Hif1α and the glycolysis pathways were upregulated in Serpina3c KD adipocytes, which were all validated by in vitro and in vivo reverse experiments. Co-immunoprecipitation (co-IP) provided evidence that Serpina3c bound nuclear factor erythroid 2-related factor 2 (Nrf2) to regulate Hif1α. Nrf2 KD reduced Hif1α and Fasn expression, decreased lipid content, and reduced the extracellular acidification rate in Serpina3c KO adipocytes. Metabolomics revealed that lactic acid (LD) levels in eWAT were responsible for adipose-associated macrophage inflammation. In summary,Serpina3c inhibits the Hif1α-glycolysis pathway and reduces de novo lipogenesis and LD secretion in adipocytes by binding to Nrf2, thereby improving HFD-induced lipid metabolism disorders and alleviating adipose tissue macrophage inflammation.

Abstract 4140191: ChREBP Drives Brown Adipocyte Differentiation and Lipid Utilization for Excess Energy Expenditure

Introduction: Although several anti-obesity drugs have become recently available, they reduce patients’ appetite, which might worsen cardiovascular disease (CVD) prognosis by malnutrition/cachexia. Brown adipose tissue (BAT) oxidizes glucose and lipids for thermogenesis, a process that requires excess energy expenditure provided by uncoupling protein 1 (UCP1) + cells. Recently, critical roles of BAT in cardio-protection have been discovered. Taken together, boosting BAT activity can be a novel anti-obesity treatment suitable for CVD patients. In this study, we aimed to establish anti-obesity strategy by manipulation of the glucose-sensing lipid-storage transcription factor, ChREBP, with unexpected function of boosting lipid utilization in BAT. Methods and Results: Through mouse/human single-cell/nucleus RNA sequencing analyses, we identified ChREBP as specifically expressed in highly thermogenic UCP1 + brown adipocytes ( Fig.A ). To investigate the role of ChREBP in BAT formation, we generated human brown adipocyte-like model from induced pluripotent stem cells (iPSC-BAT, Fig.B ). The iPSC-BAT exhibited high UCP1 and ChREBP expression, multi-locular lipid droplets, and vigorous oxygen consumption. Knocking down ChREBP strongly blocked iPSC-BAT differentiation ( Fig.C ) and impaired lipid utilization ( Fig.D ). Consistently, in vitro deletion of ChREBP in mouse BAT progenitors impeded differentiation, lipid droplet accumulation, and oxygen consumption ( Fig.E-F ). In vivo, BAT-specific deletion of all ChREBP isoforms reduced lipid accumulation and BAT characteristics. Conversely, using a new mouse model for Cre-mediated ChREBPβ overexpression, we showed that ChREBPβ overexpression in BAT (Chβ BATOX) increased BAT cellularity and activated lipogenic machineries, with paradoxical decreased lipid content, suggesting excessively activated lipid consumption in BAT ( Fig.G ). More importantly, Chβ BATOX maintained UCP1 expression and reduced fat volume ( Fig.H ) even after strongly inhibiting BAT activity. Conclusion: In summary, ChREBP is essential for BAT development and thermogenic capacity by affecting lipid utilization. Our results suggest that ChREBPβ activation may be a novel anti-obesity avenue for CVD patients.

Inclisiran-containing low-density lipoprotein cholesterol reduction effectively stabilizes atherosclerotic plaques

Abstract Background/Introduction Near-infrared spectroscopy (NIRS) allows to quantify lipid composition of coronary artery lesions. High plaque lipid content has been associated with increased adverse cardiovascular event risk. Purpose Aim of this study was to evaluate atherosclerotic plaque lipid content reduction in association with low-density lipoprotein (LDL-C) lowering on the background of intensive hypolipidaemic therapy. Methods NIRS investigation was performed in stable coronary artery disease patients having 20-50% stenosis in the proximal or middle third of a coronary artery. Segment of interest was repeatedly evaluated after 15 months. Lipid-rich plaques (LRPs) were defined as lesions with maximum lipid-core burden index within 4 mm (maxLCBI4 mm) >250. Study participants were taking high-intensity statin (atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg) with or without ezetimibe for a run-in period of 4-6 weeks. Afterwards, in patients not achieving LDL-C level <1.8 mmol/l, add-on inclisiran was started. Baseline LDL-C was defined as the level at the time of initiation of optimal lipid-lowering therapy. Statistical significance level of 0.05 was set. Results Data of 36 patients was analyzed. Mean baseline maxLCBI4 mm was 203.9, reduced by 39.8% (-81.1, 95%CI -129.2 to -33.0) at 15-month follow-up (P=0.003). In 15 patients LRPs were detected with mean baseline maxLCBI4 mm 363.5, which was decreased by 35.8% (-130.3, 95%CI -235.0 to -25.7) (P=0.020). Mean LDL-C level at baseline was 2.5 mmol/l among all participants, lowered by 32.0% (-0.8, 95%CI -1.1 to -0.5) after 15 months of treatment (P<0.001). 19 patients received inclisiran in addition to high-dose statin and optional ezetimibe therapy. In 24 patients achieving LDL-C target <1.8 mmol/l at 15-month follow-up, a significant maxLCBI4 mm reduction from 208.5 by 48.4% (-101.0, 95%CI -169.3 to -32.7) was established (P=0.010). Among those having LDL-C >1.8 mmol/l, maxLCBI4 mm reduction from 194.7 by 21.2% (-41.25, 95%CI -94.7 to 12.2) was observed, however the change was not statistically significant (P=0.114). Conclusion LDL-C lowering with high-intensity hypolipidaemic therapy, including escalation to proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, demonstrated atherosclerotic plaque stabilization by NIRS-detected lipid content decrease.

The Impact of RNA Interference on Atherosclerotic Plaque Progression: A Meta-Analysis of Preclinical Studies

Background: Atherosclerosis, a chronic inflammatory disease characterized by the buildup of plaque within arteries, remains a leading cause of cardiovascular morbidity and mortality. RNA interference (RNAi) has emerged as a promising therapeutic strategy for atherosclerosis by targeting genes involved in plaque formation and progression. This meta-analysis aimed to evaluate the efficacy of RNAi in preclinical models of atherosclerosis. Methods: A systematic search of PubMed, Embase, and Web of Science databases was conducted from January 2013 to December 2023 to identify preclinical studies investigating the impact of RNAi on atherosclerotic plaque progression. Studies utilizing various RNAi modalities (siRNA, miRNA mimics/inhibitors, shRNA) targeting different genes involved in atherosclerosis were included. The primary outcome was plaque size reduction. Secondary outcomes included changes in plaque composition, lipid profiles, and inflammatory markers. A random-effects model was used to pool data and calculate standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Results: Seven preclinical studies met the inclusion criteria, encompassing a total of 210 animals. RNAi interventions significantly reduced atherosclerotic plaque size compared to controls (SMD -1.51; 95% CI -2.36 to -0.66; p<0.00001; I²=12%). Analysis of secondary outcomes revealed favorable effects of RNAi on plaque composition, with a significant decrease in lipid content and an increase in collagen content. Furthermore, RNAi significantly improved lipid profiles by reducing total cholesterol and LDL-cholesterol levels. A significant reduction in inflammatory markers, such as TNF-α and IL-6, was also observed. Conclusion: This meta-analysis provides compelling evidence supporting the therapeutic potential of RNAi in attenuating atherosclerotic plaque progression in preclinical models. RNAi effectively reduced plaque size, improved plaque stability, and modulated lipid metabolism and inflammation.

Microplastics impair extracellular enzymatic activities and organic matter cycling in oligotrophic sandy marine sediments

Microplastics (MPs) are ubiquitous and constantly accumulating in the marine environment, especially sediments. Yet, it is not well clarified if and how their carbon backbone could interact with surrounding sediments, eventually impairing key benthic processes. We assessed the effects of a ‘pulse’ contamination event of MPs on sedimentary organic matter (OM) quantity, quality and extracellular enzymatic activities (EEAs), which are well established descriptors of benthic ecosystem functioning. Marine sediments were exposed for 30 days to environmentally relevant concentrations (∼0.2 % in weight) of naturally weathered particles (size range 70–210 μm) of polyurethane, polyethylene, and a mixture of the most common polymers that are documented to accumulate in marine sediments. Despite the low concentration, contaminated sediments showed significantly different composition of OM, showing a decrease in lipid content and increase in protein. Moreover, we document a significant decrease (over 25 %) in quantity of biopolymeric C already after 15 days of exposure, compared to controls. Contaminated sediments showed lower C degradation rates (up to −40 %) and altered EEAs, with alkaline phosphatase being ∼50 % enhanced and aminopeptidase being reduced over 35 % compared to control treatments. Overall, the effects generated by the mixture of polymers were smaller than those exerted by the same amount of a single polymer. Our results provide insights on how that MPs can significantly alter marine sedimentary biogeochemistry through altered benthic processes, that could cumulatively impair whole benthic trophic webs by enhancing the accumulation and possible longer-term storage of recalcitrant organic C in the seabed.

Exploring the physicochemical properties, fatty acids composition, and nutritional quality indices of oil derived from Chrysichthys nigrodigitatus of different sizes: Impact of processing

Fish oil, known for its health benefits due to its abundant omega-3 fatty acids, can vary in quality and nutritional value depending on the size of the fish and the processing methods used. This study focused on oil derived from Chrysichthys nigrodigitatus of varying sizes, specifically smaller fish (about 12.0 cm) and larger fish (about 26.1 cm), processed through smoking, boiling, or roasting. It was found that larger fish contained more lipids (5.74 g/100 g fresh matter) than their smaller counterparts (2.67 g/100 g fresh matter). However, all processing methods led to a decrease in lipid content per dry matter (2.3–7.4 %), with smoking causing the most significant reduction. In terms of physicochemical properties, smoking had the most impact, followed by roasting, while boiling had the least. Oxidation levels, as indicated by thiobarbituric acid, peroxide, and anisidine values, increased across all processing methods compared to fresh samples (2.0–168.0 % for larger fish and 9.3–191.1 % for smaller fish). Conversely, iodine value decreased, ranging from 14.8 % to 27.4 % for larger fish and 10.8–39.9 % for smaller fish. Boiling exhibited the smallest variation in these values, while smoking showed the highest variation. Otherwise, infrared spectroscopy revealed a consistent oil structure across samples, but unsaturation and oxidation were altered by processing. Interestingly, larger fish yielded healthier oils with a higher concentration of polyunsaturated fatty acids (26.40 %) compared to smaller fish (21.87 %). Smoking and roasting methods diminished these beneficial fatty acids, whereas boiling preserved the nutritional value. Understanding the relationship between fish size and processing methods is crucial to maintaining fish oil’s health benefits. Future research should explore these effects in different fish species, considering consumer preferences and environmental impacts.

Growth and Depuration of Off‐Flavors in Rainbow Trout Oncorhynchus Mykiss in a Partial Recirculating Aquaculture System (PRAS)

ABSTRACTIn recirculating aquaculture systems (RAS), off‐flavours accumulated in fish muscle tissue can be problematic in terms of consumer acceptance and the reputation of farmed fish products. Off‐flavours often give fish earthy, muddy, or other undesirable flavours. Typically, off‐flavours are removed during a depuration period in which fish are fasted and held in clean water. Unfortunately, this causes additional costs and delayed sales, while fish lose weight and show a decrease in lipid content. First, we studied fish growth in a partial RAS (PRAS) where the conditions are very similar to those in depuration with a water exchange rate of 4000 L kg−1 feed, compared to RAS with a 650‐L water kg−1 feed. Rainbow trout (Oncorhynchus mykiss) was reared in both systems. Our aim was to combine the benefits of a higher water exchange rate: the lack of need for biofilters and a lower accumulation of off‐flavours while obtaining stable rearing conditions. Additionally, we studied the effects of moderate feeding and H2O2 addition during depuration. The fish grew faster in a PRAS than in a RAS when fed ad libitum. Thirteen off‐flavour compounds were found in the fish flesh and 11 in the circulating water. The H2O2 addition led to decreased levels of off‐flavours in the tank water and in fish muscle. The results showed no significant differences in off‐flavours between the fed and not‐fed systems, showing that moderate feeding did not prevent a good depuration result. However, the lipid content and the overall fish weight were higher in the fed systems, which suggests more effective depuration. Increased depuration efficiency can be an important tool when considering ways to improve the profitability of production.

Transcriptome and Metabolome Based Mechanisms Revealing the Accumulation and Transformation of Sugars and Fats in Pinus armandii Seed Kernels during the Harvesting Period.

Pinus armandii seed kernel is a nutrient-rich and widely consumed nut whose yield and quality are affected by, among other things, harvesting time and climatic conditions, which reduce economic benefits. To investigate the optimal harvesting period of P. armandii seed kernels, this study determined the nutrient composition and seed kernel morphology and analyzed the gene expression and metabolic differences of P. armandii seed kernels during the harvesting period by transcriptomics and metabolomics. The results revealed that during the maturation of P. armandii seed kernels, there was a significant increase in the width, thickness, and weight of the seed kernels, as well as a significant accumulation of sucrose, soluble sugars, proteins, starch, flavonoids, and polyphenols and a significant decrease in lipid content. In addition, transcriptomic and metabolomic analyses of P. armandii seed kernels during the harvesting period screened and identified 103 differential metabolites (DEMs) and 8899 differential genes (DEGs). Analysis of these DEMs and DEGs revealed that P. armandii seed kernel harvesting exhibited gene-metabolite differences in sugar- and lipid-related pathways. Among them, starch and sucrose metabolism, glycolysis, and gluconeogenesis were associated with the synthesis and catabolism of sugars, whereas fatty acid degradation, glyoxylate and dicarboxylic acid metabolism, and glycerophospholipid metabolism were associated with the synthesis and catabolism of lipids. Therefore, the present study hypothesized that these differences in genes and metabolites exhibited during the harvesting period of P. armandii seed kernels might be related to the accumulation and transformation of sugars and lipids. This study may provide a theoretical basis for determining the optimal harvesting time of P. armandii seed kernels, changes in the molecular mechanisms of nutrient accumulation, and quality directed breeding.

Pea protein – gum Arabic gel addition as ingredient to increase protein, fiber and decrease lipid content in muffins without impair the texture and intestinal microbiota

This study evaluated the use of a protein-polysaccharide gel (PGEL) as a muffin ingredient, and its effect on the nutritional, textural, and gut microbiome profiles. PGEL was generated by complex coacervation with Pea protein and Gum Arabic. A mixture design was performed with different flour, lipids, and PGEL proportions, where Tx9 (26 % PGEL) showed improved physicochemical characteristics. Optimization was performed using 3 variables, hardness, protein content, and in vitro protein digestibility, to generate an optimal muffin with PGEL (PGEL-Muffin). PGEL-Muffin had a positive effect in its nutritional content and texture (protein: 12.03 %, fiber: 7.90 %, lipids: 9.23 %, and hardness: 4.41 N) compared to a muffin without protein addition (Control) and a muffin with added pea protein powder (Powder-Muffin). PGEL-Muffin did not modify gut microbiome using an ex-vivo system after 4-days of administration. PGEL ingredient could be an opportunity to develop nutritionally improved products without a negative impact on textural properties.

Chronic UVB exposure induces hepatic injury in mice: Mechanistic insights from integrated multi-omics

Chronic UVB exposure poses a significant threat to both skin and visceral health. In recent years, the adverse role of chronic UVB exposure in liver health has been suggested but not fully elucidated. This study aims to comprehensively investigate the effects of chronic UVB exposure on liver health in male SKH-1 hairless mice and clarify potential mechanisms through multi-omics approaches. The findings suggested that 10-week chronic skin exposure to UVB not only triggers hepatic inflammation and oxidative stress but also, more importantly, results in lipid metabolism abnormalities in the liver. Hepatic transcriptomic analysis revealed significant alterations in various signaling pathways and physiological processes associated with inflammation, oxidative stress, and lipid metabolism. Further lipidomic analysis illustrated significant changes in the metabolism of glycerolipids, sphingolipids, and glycerophospholipids in the liver following chronic UVB exposure. The 16S rRNA sequencing analysis indicated that chronic UVB exposure disrupts the structure and function of the microbiota. In search of potential mechanisms used by the microbiome to regulate the hepatic disease morphology, we filtered mouse fecal supernatants and cultured the supernatants with HepG2 cells. Fecal supernatant from UVB-exposed mice induced increased secretion of the inflammatory cytokine IL-8, accumulation of MDA, reduced SOD activity, and decreased lipid content in normal hepatic cells. In summary, skin chronic exposure to UVB induces multiple liver injuries and gut microbiota dysbiosis in mice and gut microbiota metabolites may be one of the contributing factors to hepatic injury caused by chronic UVB exposure. These discoveries deepen the comprehension of the health risks associated with chronic UVB exposure.

Assessment of the Anti-Adipogenic Effect of Crateva religiosa Bark Extract for Molecular Regulation of Adipogenesis: In Silico and In vitro Approaches for Management of Hyperlipidemia Through the 3T3-L1 Cell Line.

This study aimed to determine the phytoconstituents of Crateva religiosa bark (CRB) and evaluate the hypolipidemic effect of bioactive CRB extract by preventing adipocyte differentiation and lipogenesis. After performing the preliminary phytochemicals screening, the antioxidant activity of CRB extracts was determined through a DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay. Ethyl acetate extract (CREAE) and ethanol extract (CRETE) of CRB were selected for chromatographic evaluation. The antihyperlipidemic potential was analyzed by molecular docking through the PKCMS software platform. Further, a 3T3-L1 cell line study via In vitro sulforhodamine B assay and western blotting was performed to confirm the prevention of adipocyte differentiation and lipogenesis Results: The total phenolic contents in CREAE and CRETE were estimated as 29.47 and 81.19 μg/mg equivalent to gallic acid, respectively. The total flavonoid content was found to be 8.78 and 49.08 μg/mg, equivalent to quercetin in CREAE and CRETE, respectively. CRETE exhibited greater scavenging activity with the IC50 value of 61.05 μg/ mL. GC-MS analysis confirmed the presence of three bioactive molecules, stigmasterol, gamma sitosterol, and lupeol, in CRETE. Molecular docking studies predicted that the bioactive molecules interact with HMG-CoA reductase, PPARγ, and CCAAT/EBP, which are responsible for lipid metabolism. In vitro, Sulforhodamine B assays revealed that CRETE dose-dependently reduced cell differentiation and viability. Cellular staining using 'Oil Red O' revealed a decreased lipid content in the CRETE-treated cell lines. CRETE significantly inhibited the induction of PPARγ and CCAAT/EBP expression, as determined through protein expression via western blotting. The influence of CRETE on lipid metabolism in 3T3-L1 cells is potentially suggesting a new approach to managing hyperlipidemia.

Effect of salting time and drying method on physicochemical characteristics of dried meat from the longissimus muscle of Algerian dromedary camels

The present study aims to evaluate the effects of a cold brine (4 °C) pre-treatment on the quality of camel meat. The studied parameters are moisture content, macronutrient composition, color, pH, and shrinkage, before and after drying. Five groups of 108 camel meat slices with dimensions of 100 ×20 x 4 mm (length x width x thickness) were constituted. The control group (group 1) received no treatment. Groups 2 and 3 were immersed for 30 and 90 minutes respectively in a 19 % sodium chloride solution at 4 °C, then sun-dried. As for groups 4 and 5, they were treated in the same way for 30 and 90 minutes, but oven-dried at 65 °C. Results demonstrate that increasing the soaking time reduced the drying duration from 20 to 16 hours for oven drying and 14–12 hours for sun drying. Moisture content decreased from 73.94±0.31 % to 13.33±0.15 %, while protein levels decreased from 75.76±0.04 % to 74.465±0.02 % and 74.97±0.04 % for oven drying and 74.25±0.07 % to 74.51±0.01 % for sun drying after 30 and 90 minutes of soaking, respectively. A decrease in lipid content from 21.65±0.04 % to 19.10±0.06 % and 19.14±0.08 % was also observed during oven drying and 19.33±0.07 % to 19.12±0.09 % for sun drying. Sodium levels increased from 260.47±1.46 mg/100 g to 1690.36±1.94–1712.11±5.14 mg/100 g for oven drying and 1704.48±7.16 mg/100 g - 1714.89±4.18 mg/100 g for sun drying. Longer soaking times increased total color variation for both drying methods. By using cold brine, the nutrients in the muscle slices are preserved and the final product is lower in salinity.

The YY1-CPT1C signaling axis modulates the proliferation and metabolism of pancreatic tumor cells under hypoxia

Carnitine palmitoyltransferase 1C (CPT1C) is an enzyme that regulates tumor cell proliferation and metabolism by modulating mitochondrial function and lipid metabolism. Hypoxia, commonly observed in solid tumors, promotes the proliferation and progression of pancreatic cancer by regulating the metabolic reprogramming of tumor cells. So far, the metabolic regulation of hypoxic tumor cells by CPT1C and the upstream mechanisms of CPT1C remain poorly understood. Yin Yang 1 (YY1) is a crucial oncogene for pancreatic tumorigenesis and acts as a transcription factor that is involved in multiple metabolic processes. This study aimed to elucidate the relationship between YY1 and CPT1C under hypoxic conditions and explore their roles in hypoxia-induced proliferation and metabolic alterations of tumor cells. The results showed enhancements in the proliferation and metabolism of PANC-1 cells under hypoxia, as evidenced by increased cell growth, cellular ATP levels, up-regulation of mitochondrial membrane potential, and decreased lipid content. Interestingly, knockdown of YY1 or CPT1C inhibited hypoxia-induced rapid cell proliferation and vigorous cell metabolism. Importantly, for the first time, we reported that YY1 directly activated the transcription of CPT1C and clarified that CPT1C was a novel target gene of YY1. Moreover, the YY1 and CPT1C were found to synergistically regulate the proliferation and metabolism of hypoxic cells through transfection with YY1 siRNA to CRISPR/Cas9-CPT1C knockout PANC-1 cells. Taken together, these results indicated that the YY1-CPT1C axis could be a new target for the intervention of pancreatic cancer proliferation and metabolism.

LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism

LIMA1 is a LIM domain and Actin binding 1 protein that acts as a skeleton protein to promote cholesterol absorption, which makes it an ideal target for interfering with lipid metabolism. However, the detailed regulation of LIMA1 remains unclear. Here, we identified that ring finger protein 40 (RNF40), an E3 ubiquitin ligase previously known as an epigenetic modifier to increase H2B ubiquitination, mediated the ubiquitination of LIMA1 and thereby promoted its degradation in a proteasome-dependent manner. Fraction studies revealed that the 1–166aa fragment of LIMA1 was indispensable for the interaction with RNF40, and at least two domains of RNF40 might mediate the association of RNF40 with LIMA1. Notably, treatment with simvastatin dramatically decreased the levels of CHO and TG in control cells rather than cells with overexpressed LIMA1. Moreover, RNF40 significantly decreased lipid content, which could be reversed by LIMA1 overexpression. These findings suggest that E3 ubiquitin ligase RNF40 could directly target LIMA1 and promote its protein degradation in cytoplasm, leading to the suppression of lipid accumulation mediated by LIMA1. Collectively, this study unveils that RNF40 is a novel E3 ubiquitin ligase of LIMA1, which underpins its high therapeutic value to combat dysregulation of lipid metabolism.

Energy strategy alteration, rather than toxicity itself, interferes with the population fluctuation of Brachionus plicatilis exposed to water-accommodated fractions (WAFs) of crude oil

Oil spills are reported to have conflicting impacts of either injury or resilience on zooplankton communities, and physiological plasticity is speculated to be the possible causative factor. But how? An explanation was sought by exposing the marine rotifer Brachionus plicatilis to a series of water-accommodated fractions (WAFs) of crude oil under controlled laboratory conditions, and population dynamics, which is the core issue for zooplankton facing external stress, were analyzed. The total hydrocarbon concentration of WAFs was quickly degraded from a concentration of 5.0 mg L−1 to half within 24 h and then remained stable. No acute lethality was observed; only motion inhibition was observed in the group treated with 10 %, 50 % and 100 % WAFs, which occurred simultaneously with inhibition of feeding and filtration. However, sublethal exposure to the WAFs concentration series presented stimulation impacts on reproduction and even the population of B. plicatilis. The negative correlation between motion and reproduction seemed to indicate that a shift in the distribution of individual energy toward reproduction rather than motion resulted in increased reproduction after exposure to WAFs. More evidence from transmission electron microscopy (TEM) revealed ultrastructural impairment in both the ovaries and cilia in each treated group, and imbalance in mitochondrial numbers was one of the distinct features of alteration. WAFs stress may alter the energy utilization and storage paradigm, as indicated by the significant elevation in glycogen and the significant decrease in lipid content after WAFs exposure. Further evidence from metabolomics analysis showed that WAFs stress increased the level of lipid metabolism and inhibited some of the pathways in glucose metabolism. Sublethal acute toxicity was observed only in the first 24 h with WAFs exposure, and an energy strategy consisting of changes in the utilization and storage paradigm and reallocation is responsible for the population resilience of B. plicatilis during oil spills.

Integrated transcriptomic and lipidomic analysis provides key insights into lipid content changes during pecan (Carya illinoensis) fruit development.

Pecans [Carya illinoinensis (Wangenh.) K. Koch] are highly valued for their abundance of quality healthy lipids, positively impacting human health and making themselves a preferred choice for nutritionally rich foods. However, a comprehensive understanding of the high-resolution characteristics of pecan fruit lipid composition and its dynamic changes, as well as the transfer between embryo and pericarp during development, remains incomplete. In this study, through integrated multi-omics analysis, we observed significant spatiotemporal heterogeneity in lipid changes between the pericarp and embryo. It showed smaller fluctuations and more stable lipid levels in the pericarp while exhibiting a dynamic pattern of initially increasing and then decreasing lipid content in the embryo. In this study, a total of 52 differentially expressed genes were identified, related to fatty acid synthesis and metabolism pathways in the two tissues, with changes in oleic acid and linoleic acid composition being the primary features of the embryo. This research lays the foundation for further understanding the differential regulation mechanisms of lipid metabolism between embryo and pericarp. Overall, this study filled the knowledge gap regarding dynamic changes in pericarp lipid metabolites, provided crucial insights into the lipid metabolism network during pecan fruit development, and established a scientific basis for the genetic improvement of pecan crops.

LincRNA00907 promotes NASH progression by targeting miRNA-942-5p/TAOK1.

The study aims to examine the involvement of lincRNA00907 in the advancement of non-alcoholic steatohepatitis (NASH). The examination was conducted to assess the expression of linc00907 in liver tissues from NASH patients and healthy individuals. High-fat diets induced NASH in mouse models, while palmitic acid/oleic acid treatment was used to create in vitro cell models. Various techniques, such as qRT-PCR, Oil Red O staining and gene knockdown/overexpression, were used to assess the impact of linc00907 on genes related to lipid metabolism and immunity, as well as intracellular lipid accumulation. Furthermore, dual-luciferase reporter assays were carried out to confirm the connection between miRNA-942-5p and linc00907 or TAOK1 mRNA. Linc00907 was found to be significantly upregulated in both NASH patients and NASH mouse models. Overexpression of linc00907 led to an increase in intracellular lipid accumulation, while knockdown of linc00907 resulted in decreased lipid content. It was found that miRNA-942-5p binds with linc00907, and their interaction was confirmed in dual-luciferase reporter assays. Additionally, TAOK1 was predicted to be a downstream target of miRNA-942-5p, and the upregulation of TAOK1 due to linc00907 was reversed by miRNA-942-5p overexpression. linc00907 overexpression reduces apoptosis but can be reversed by TAOK1 knockdown. The reduction of TAOK1 counteracted the impact of linc00907 on gene expression associated with lipid metabolism and immunity, as well as on the accumulation of intracellular lipids. Our research suggests that linc00907 functions as a competitive endogenous RNA (ceRNA) by sequestering miRNA-942-5p, thus increasing the expression of TAOK1 and encouraging lipid accumulation in hepatocytes, leading to the aggravation of NASH development. Targeting the linc00907/miRNA-942-5p/TAOK1 axis may hold therapeutic potential for the treatment of NASH.

Gkongensin A, an HSP90β inhibitor, improves hyperlipidemia, hepatic steatosis, and insulin resistance

The prevalence of obesity and its primary associated comorbidities, such as type 2 diabetes and fatty liver disease, has reached epidemic proportions, with no successful treatment available at present. Heat shock protein 90 (HSP90), a crucial chaperone, plays a key role in de novo lipogenesis (DNL) by stabilizing and maintaining sterol regulatory element binding protein (SREBP) activity. Kongensin A (KA), derived from Croton kongensis, inhibits RIP3-mediated necrosis, showing promise as an anti-necrotic and anti-inflammatory agent. It is not yet clear if KA, acting as an HSP90 inhibitor, can enhance hyperlipidemia, hepatic steatosis, and insulin resistance in obese individuals by controlling lipid metabolism. In this study, we first found that KA can potentially decrease lipid content at the cellular level. C57BL/6J mice were given a high-fat diet (HFD) and received KA and lovastatin through oral administration for 7 weeks. KA improved hyperlipidemia, fatty liver, and insulin resistance, as well as reduced body weight in diet-induced obese (DIO) mice, with no significant alteration in food intake. In vitro, KA suppressed DNL and reduced the amounts of mSREBPs. KA promoted mSREBP degradation via the FBW7-mediated ubiquitin-proteasome pathway. KA decreased the level of p-Akt Ser308, and p-GSK3β Ser9 by inhibiting the interaction between HSP90β and Akt. Overall, KA enhanced hyperlipidemia, hepatic steatosis, and insulin resistance by blocking SREBP activity, thereby impacting the FBW7-controlled ubiquitin-proteasome pathway.

The Role of Acyl-CoA Synthetase 1 in Bioactive Lipid Accumulation and the Development of Hepatic Insulin Resistance.

The liver plays a crucial role in glucose metabolism. Obesity and a diet rich in fats (HFD) contribute to the accumulation of intracellular lipids. The aim of the study was to explore the involvement of acyl-CoA synthetase 1 (ACSL1) in bioactive lipid accumulation and the induction of liver insulin resistance (InsR) in animals fed an HFD. The experiments were performed on male C57BL/6 mice divided into the following experimental groups: 1. Animals fed a control diet; 2. animals fed HFD; and 3. HFD-fed animals with the hepatic ACSL1 gene silenced through a hydrodynamic gene delivery technique. Long-chain acyl-CoAs, sphingolipids, and diacylglycerols were measured by LC/MS/MS. Glycogen was measured by means of a commercially available kit. The protein expression and phosphorylation state of the insulin pathway was estimated by Western blot. HFD-fed mice developed InsR, manifested as an increase in fasting blood glucose levels (202.5 mg/dL vs. 130.5 mg/dL in the control group) and inhibition of the insulin pathway, which resulted in an increase in the rate of gluconeogenesis (0.420 vs. 0.208 in the control group) and a decrease in the hepatic glycogen content (1.17 μg/mg vs. 2.32 μg/mg in the control group). Hepatic ACSL1 silencing resulted in decreased lipid content and improved insulin sensitivity, accounting for the decreased rate of gluconeogenesis (0.348 vs. 0.420 in HFD(+/+)) and the increased glycogen content (4.3 μg/mg vs. 1.17 μg/mg in HFD(+/+)). The elevation of gluconeogenesis and the decrease in glycogenesis in the hepatic tissue of HFD-fed mice resulted from cellular lipid accumulation. Inhibition of lipid synthesis through silencing ACSL1 alleviated HFD-induced hepatic InsR.