Affect Lipid Metabolism Research Articles

Exposure to microplastics affects fatty acid composition in the Japanese quail depending on sex and particle size

Plastic ingestion in birds is a widespread phenomenon of increasing concern. However, little is known about how exposure to microplastics (MP) affects the health of birds. In other organisms, MP exposure alters lipid metabolism and composition. If also true in birds, this could affect their fitness, especially since birds heavily rely on lipids during migration and egg production. Therefore, the aim of this study was to determine if ingestion of MP (polypropylene and polyethylene collected in nature) in two size ranges, large (3 mm) and small (<125 μm), affects lipid metabolism in the Japanese quail (Coturnix japonica). We orally exposed 55 one-week-old quail during 5 weeks to a total of 600 mg of MP in sizes of either large, small, or a mixture of both. After the exposure period, females fed small MP had higher liver masses compared to control females (on average ± SD, 8.95 ± 2.3 g vs. 6.34 ± 1.0 g), while liver lipid content did not differ in either males or females. The levels of monounsaturated fatty acids were lower in females exposed to large MP and the mixture of both MP sizes compared to controls. Females exposed to MP also had different levels of oleic- (18:1) and palmitoleic (16:1) acid compared to controls dependent on MP size. Exposure to small MP increased levels of palmitic- (16:0) and palmitoleic (16:1) acid in both males and females suggesting a possible increase in de novo fatty acid synthesis. Taken together, our results point towards a sex-specific sensitivity to MP as well as size-dependent MP effects on lipid metabolism in birds. Disruption of fatty acid composition could affect important life stages in female birds, such as migration and egg-laying. We stress the importance of further research focused on determining the mechanisms of action of MP on lipid metabolism.

A case report of Tangier disease presents with acute sensorimotor polyneuropathy and its treatment approach

Polyneuropathy is a frequently encountered clinical presentation where peripheral nerves are affected due to the same cause and physiopathological processes. We report a case of acute sensorimotor polyneuropathy in a patient with Tangier disease (TD) who was treated with miglustat which is a glycosphingolipid synthesis inhibitor. TD is a very rare genetic disorder caused by mutations in the ATP-binding cassette transporter A1 (ABCA1) gene which encodes the cholesterol efflux regulatory protein. It leads to accumulation of cholesterol esters within various tissues and affects lipid metabolism by deficiency of high-density lipoprotein (HDL) in the blood. Due to the accumulation of cholesterol esters in Schwann cells, it could provoke polyneuropathy in TD. Our case presented to our clinic with quadriparesis and after treated with miglustat therapy his weakness regressed.

MiR-1182-mediated ALDH3A2 inhibition affects lipid metabolism and progression in ccRCC by activating the PI3K-AKT pathway

In clear cell renal cell carcinoma (ccRCC), dysregulated lipid metabolism plays a pivotal role in tumor initiation and progression. This study delves into the unexplored landscape of Dysregulated Aldehyde Dehydrogenase 3 Family Member A2 (ALDH3A2) in ccRCC. Using a combination of "fatty acid metabolism" dataset analysis and differentially expressed genes (DEGs) derived from Gene Expression Omnibus (GEO) database, potential metabolic regulators in ccRCC were identified. Subsequent investigations utilizing public databases, clinical samples, and in vitro experiments revealed that ALDH3A2 was down-regulated in ccRCC, mediated by miR-1182, highlighting its role as an independent prognostic factor for patient survival. Functionally, ALDH3A2 exhibited tumor-suppressive properties, impacting ccRCC cell phenotypes and influencing epithelial-mesenchymal transition. Mechanistically, silencing ALDH3A2 promoted lipid accumulation in ccRCC cells by activating the PI3K-AKT pathway, thereby promoting tumor progression. These findings shed light on the critical role of the miR-1182/ALDH3A2 axis in ccRCC tumorigenesis, emphasizing the potential for targeting lipid metabolism as a promising anti-cancer strategy.

AML Inhibits Lipid Uptake By the Liver through an HGF/c-MET Dependent Mechanism Which Results in an Increased Supply of Free Fatty Acid to the Tumor

Acute myeloid leukemia (AML) requires a high metabolic turnover to allow for constant expansion. We and others have previously shown that primary human AML blasts rely on fatty acid (FA)-oxidation for survival and proliferation. (Shafat MS, et al. 2017, Jones CL, et al. 2018). The liver plays a major role in carbohydrate, protein, amino acid, and lipid metabolism (Hodson L, and Gunn PJ. 2019). Given that AML is a FA dependent tumor, we have studied the interactions between AML and the liver, and specifically how these affect lipid metabolism, the availability of pro-tumoral FFA and ultimately the mechanism by which this supports AML growth. To understand the role of lipid metabolism we used two syngeneic models of AML (HOXA9/Meis1 or MN1). When engrafted with AML cells, mice body weight during the latter stages of disease. After sacrifice, the size of epididymal and inguinal fat pads were significantly reduced in mice with AML compared to controls. Mice with AML also had elevated free fatty acid (FFA) and reduced glucose in the plasma. We and others have shown that AML induces lipolysis of white adipose tissue for uptake by blasts and resulting in tumor expansion (Shafat MS, et al. 2017, Ye H, et al. 2016). Since the liver is the master regulator of available FA in the plasma, we isolated livers from AML engrafted mice. Transcriptomics revealed down-regulation of genes involved in FA uptake and metabolism. RT-qPCR of RNA isolated from liver samples confirmed these results showing down-regulation of FA transport proteins, (FABP1, SLC27A2, SLC27A5, and CD36) and FA metabolism genes (CPT1, ACADM, and HMGCS2). Furthermore, primary hepatocytes isolated and cultured with AML conditioned media showed a down-regulation of FA uptake and metabolism genes. These data support the hypothesis that AML secretes a factor that alters lipid metabolism in the liver. To discover the factor that AML secretes, and which regulates FA uptake and metabolism in the liver, a proteome profile of the serum from AML engrafted mice was compared to conditioned media from AML cultured cells. Pathway analysis revealed hepatocyte growth factor (HGF), IL-1B and Granulocyte colony stimulating factor (G-CSF) as possible key factors involved in liver FA metabolism (Jing Y, et al. 2019, Kaibori M, et al. 2002). In vitro gene expressions analysis of primary hepatocytes revealed that addition of HGF to the medium, but not Il-1b or G-CSF, inhibited expression of FA uptake genes. In addition, using Seahorse mitochondrial stress kit we confirmed that primary hepatocytes decreased FA oxidation when cultured with AML conditioned media or HGF. Next, we confirmed that AML derived HGF was responsible for inhibition of hepatocyte FA genes by using a neutralizing antibody to HGF which blocked the transcriptional changes previously observed in hepatocytes cultured in AML conditioned media. This showed that AML derived HGF downregulates hepatocyte FA uptake and metabolism. Finally, to determine the role of AML in the uptake of FA by hepatocytes, cultures of primary murine hepatocytes were pretreated with AML conditioned media or HGF with and without neutralizing antibody. A BODIPY conjugated long chain FA was then added to the culture. Images analysis showed hepatocytes had reduced lipid uptake in the presence of AML condition media or HGF, but this was restored with the addition of HGF neutralizing antibody. Here we report that AML inhibition of lipid uptake in the liver, through an HGF dependent mechanism, increases the availability of plasma FA and forms a fundamental part of the AML disease. Ongoing work to develop our understanding of how AML increases access to FA to aid proliferation, may aid in the development of new therapeutics to target liver metabolism in combination with other AML therapies.

Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia

BackgroundDiet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia.ResultsWe demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum and Ruminococcaceae UCG-010, which then elevated serum cholicacid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), reduced bile acid synthesis and increased cholesterol accumulation via the hepatic farnesoid X receptor-small heterodimer partner (FXR-SHP) axis. Nevertheless, high-fat diet led to decreased Muribaculum in the humanized dyslipidemia mice induced by FMT-dd, which resulted in reduced intestinal hyodeoxycholic acid (HDCA), raised bile acid synthesis and increased lipid absorption via the intestinal farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis.ConclusionsOur studies implicated that intestinal FXR is responsible for the regulation of lipid metabolism in diet-induced dyslipidemia mediated by gut microbiota-bile acid crosstalk.27dVNVWG4xVHYhT6VNwbbKVideo

Circadian clock factors regulate the first condensation reaction of fatty acid synthesis in Arabidopsis

The circadian clock regulates temporal metabolic activities, but how it affects lipid metabolism is poorly understood. Here, we show that the central clock regulators LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) regulate the initial step of fatty acid (FA) biosynthesis in Arabidopsis. Triacylglycerol (TAG) accumulation in seeds was increased in LHY-overexpressing (LHY-OE) and decreased in lhycca1 plants. Metabolic tracking of lipids in developing seeds indicated that LHY enhanced FA synthesis. Transcript analysis revealed that the expression of genes involved in FA synthesis, including the one encoding β-ketoacyl-ACP synthase III (KASIII), was oppositely changed in developing seeds of LHY/CCA1-OEs and lhycca1. Chromatin immunoprecipitation, electrophoretic mobility shift, and transactivation assays indicated that LHY bound and activated the promoter of KASIII. Furthermore, phosphatidic acid, a metabolic precursor to TAG, inhibited LHY binding to KASIII promoter elements. Our data show a regulatory mechanism for plant lipid biosynthesis by the molecular clock.

Germline proliferation trades off with lipid metabolism in Drosophila.

Little is known about the metabolic basis of life-history trade-offs but lipid stores seem to play a pivotal role. During reproduction, an energetically highly costly process, animals mobilize fat reserves. Conversely, reduced or curtailed reproduction promotes lipid storage in many animals. Systemic signals from the gonad seem to be involved: Caenorhabditis elegans lacking germline stem cells display endocrine changes, have increased fat stores and are long-lived. Similarly, germline-ablated Drosophila melanogaster exhibit major somatic physiological changes, but whether and how germline loss affects lipid metabolism remains largely unclear. Here we show that germline-ablated flies have profoundly altered energy metabolism at the transcriptional level and store excess fat as compared to fertile flies. Germline activity thus constrains or represses fat accumulation, and this effect is conserved between flies and worms. More broadly, our findings confirm that lipids represent a major energetic currency in which costs of reproduction are paid.

In vitro Adipocyte Differentiation Inhibition and in vivo Effects on Lipid Metabolism in High-Fat Diet-Induced Obesity of Euphorbia humifusa.

Euphorbia humifusa Willd (Euphorbiaceae) is a functional raw material with various pharmacological activities. This study aimed to validate the inhibitory effect of Euphorbia humifusa extract (EHE) on adipocyte differentiation in vitro and in a high-fat-diet (HFD)-induced mouse model to evaluate the E.a humifusa as a novel anti-obesity and lipid metabolism enhancer agent. EHE effects on obesity and lipid metabolism were assessed in HFD-induced obese mice after 4-week treatments. Results were compared among four treatment groups (n = 7/group): low fat diet (LFD), high fat diet (HFD), and HFD-induced obese mice treated with either 100 or 200 mg/kg/day EHE (EHE100 and EHE200, respectively). EHE (50 to 200 μg/ml) and quercetin (50 μg/ml) significantly reduced 3T3-L1 preadipocyte differentiation (p < 0.001), in a concentration-dependent manner. EHE affected lipid metabolism, as evidenced by changes in serum lipid components. The HFD-EHE100 and HFD-EHE200 groups exhibited significantly (p < 0.05) reduced triglycerides (TG, 97.50 ± 6.56 and 82.50 ± 13.20 mg/dL, respectively) and low-density lipoprotein-cholesterol (LDL-c: 40.25 ± 4.99 and 41.25 ± 6.36 mg/dL, respectively) compared to the HFD group (TG: 129.25 ± 19.81 mg/dL; LDL-c: 51.75 ± 11.59 mg/dL). Haematoxylin and Eosin (H&E) and Oil red O staining showed that EHE markedly reduced lipid accumulation and inhibited lipogenesis in the liver. Interestingly, EHE significantly (p < 0.01) reduced the expression of adipogenic transcription factors in liver tissue. Our results indicated that EHE has the potential to be a therapeutic agent for addressing obesity and lipid metabolism.

SBC (Sanhuang Xiexin Tang combined with Baihu Tang plus Cangzhu) alleviates NAFLD by enhancing mitochondrial biogenesis and ameliorating inflammation in obese patients and mice

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis—a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.

Research progress in the correlation between SREBP/PCSK9 pathway and lipid metabolism disorders induced by antipsychotics.

Antipsychotic medications are commonly used to treat schizophrenia, but they can have negative effects on lipid metabolism, leading to an increased risk of cardiovascular diseases, reduced life expectancy, and difficulties with treatment adherence. The specific mechanisms by which antipsychotics disrupt lipid metabolism are not well understood. Sterol regulatory element-binding proteins (SREBPs) are important transcriptional factors that regulate lipid metabolism. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene regulated by SREBPs, plays a critical role in controlling levels of low-density lipoprotein cholesterol (LDL-C) and has become a focus of research on lipid-lowering drugs. Recent studies have shown that antipsychotic drugs can affect lipid metabolism through the SREBP/PCSK9 pathway. A deep understanding of the mechanism for this pathway in antipsychotic drug-related metabolic abnormalities will promote the prevention of lipid metabolism disorders in patients with schizophrenia and the development and application of new drugs.

Long-Term Tetrabromobisphenol A Exposure Induces Gut Microbiota Imbalance and Metabolic Disorders via the Peroxisome Proliferator-Activated Receptor Signaling Pathway in the Regenerated Gut of Apostichopus japonicus.

Tetrabromobisphenol A (TBBPA), a commonly utilized brominated flame retardant, is found in many types of abiotic and biotic matrices. TBBPA can increase oxidative stress, disrupt the endocrine system, cause neurodevelopmental disorders and activate peroxisome proliferator-activated receptors to modulate lipid deposits in aquatic animals. However, the toxic mechanism of TBBPA on the gut microbiota and intestinal health remains unclear. Apostichopus japonicus is an ideal model for studying the relationship between environmental contaminants and intestinal health due to its unique capacity for evisceration and quickly regenerated intestine. In the present study, we investigated the toxic mechanism of TBBPA on the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. The results show that TBBPA exposure decreased the health of the regenerated intestine and the enzymatic activities, alpha diversity indices, and the relative abundance of the gut microbiota. Transcriptome analysis shows that TBBPA exposure affected lipid metabolism via the PPAR signaling pathway during the process of intestinal regeneration in A. japonicus, suggesting that TBBPA exposure can affect the composition and function of the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. These results provide a basis for further research on the potential toxicity of TBBPA to the intestinal health in animals.

Association between oral contraceptives with lipid profile: results from Hoveyzeh cohort study (HCS)

BackgroundOral contraceptives (OCs) affect lipid metabolism, which can cause hyperlipidemia, a risk factor for cardiovascular diseases. The study was designed to evaluate the possible changes in lipid profile due to using OCs.MethodsA cross-sectional study was conducted from April 2016 to August 2018 among women from the baseline phase Hoveyzeh cohort study (HCS). Sociodemographic data, anthropometric measurements, physical activity, and biochemical blood tests were measured for every participant. Multiple logistic regression was used to adjust the potential confounders.ResultsAmong 2272 participants, 1549 women were OC users, and 723 women were non-user OCs. The mean lipid profile levels were higher in OC users than in non-user OCs. Odds of abnormal Total cholesterol (TC) in OC users were significantly higher than those of non-users OCs [OR = 1.29 (95% CI;1.05 to 1.58)]. Also, the Odds of abnormal low-density lipoprotein (LDL) in OC users was 12% higher than in non-user OCs. However, no significant relationship between abnormal LDL with Oral Contraceptive Pills (OCPs) was observed.ConclusionsThe mean lipid profile was higher in OC users compared to non-user OCs. This finding highlights the need for public health strategies to prevent and detect hyperlipidemia in user OCs.

Lipotoxicity, ER Stress, and Cardiovascular Disease: Current Understanding and Future Directions.

The endoplasmic reticulum (ER) is a sub-cellular organelle that is responsible for the correct folding of proteins, lipid biosynthesis, calcium storage, and various post-translational modifications. In the disturbance of ER functioning, unfolded or misfolded proteins accumulate inside the ER lumen and initiate downstream signaling called unfolded protein response (UPR). The UPR signaling pathway is involved in lipolysis, triacylglycerol synthesis, lipogenesis, the mevalonate pathway, and low-density lipoprotein receptor recycling. ER stress also affects lipid metabolism by changing the levels of enzymes that are involved in the synthesis or modifications of lipids and causing lipotoxicity. Lipid metabolism and cardiac diseases are in close association as the deregulation of lipid metabolism leads to the development of various cardiovascular diseases (CVDs). Several studies have suggested that lipotoxicity is one of the important factors for cardiovascular disorders. In this review, we will discuss how ER stress affects lipid metabolism and their interplay in the development of cardiovascular disorders. Further, the current therapeutics available to target ER stress and lipid metabolism in various CVDs will be summarized.

The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging

While disorders in lipid metabolism have been associated with aging and age-related diseases, how lipid metabolism is regulated during aging is poorly understood. Here, we characterize the Drosophila endoribonuclease CG2145, an ortholog of mammalian EndoU that we named Age-related lipid regulator (Arlr), as a regulator of lipid homeostasis during aging. In adult adipose tissues, Arlr is necessary for maintenance of lipid storage in lipid droplets (LDs) as flies age, a phenotype that can be rescued by either high-fat or high-glucose diet. Interestingly, RNA-seq of arlr mutant adipose tissues and RIP-seq suggest that Arlr affects lipid metabolism through the degradation of the mRNAs of lipolysis genes – a model further supported by the observation that knockdown of Lsd-1, regucalcin, yip2 or CG5162, which encode genes involved in lipolysis, rescue the LD defects of arlr mutants. In addition, we characterize DendoU as a functional paralog of Arlr and show that human ENDOU can rescue arlr mutants. Altogether, our study reveals a role of ENDOU-like endonucleases as negative regulator of lipolysis.

Potential role of Bcl2 in lipid metabolism and synaptic dysfunction of age-related hearing loss

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.

Potency of fermented jicama extract cultured with Lactobacillus plantarum B1765 for producing short chain fatty acid

Short-chain fatty acid (SCFA) is the end product of inulin metabolism, which has various health benefits, such as affecting lipid metabolism and as an antidiabetic agent. This research studied the effect of the fermentation time of jicama extract with Lactobacillus plantarumB1765 as a starter culture on producing SCFA. Fermentation was conducted for 2, 12, 24, and 36 hours at a temperature of 37°C with 5% (v/v) of the starter culture, then determined the growth of LAB, pH, Total Titratable Acid (TTA), fructose, and Short Chain Fatty Acid content. The total LAB count was measured using the Total Plate Count; fructose was measured using the Nelson-Somogyi method, while SCFA was measured using HPLC with eluents H3PO4 0.1% and acetonitrile 25%. The length of fermentation affected the increase in total Lactic Acid Bacteria (LAB), Total titratable acidity (TTA), fructose, SCFA, and the decrease in pH. The results showed that the optimal growth of Total LAB at 24 hours of fermentation correlated with fructose content, but increasing TTA and SCFA until 36 hours of fermentation and pH decreased to 3,92 at the end of fermentation and decreasing pH due to lactic acid and SCFA producing. SCFA was identified as consisting of acetic acid (1.31±0.006 mg/mL), propionic acid (1.58±0.0055mg/mL), and butyric acid (1.05±0.0038mg/mL), with the highest SCFA was propionic acid. Therefore, fermented jicama extract with Lactobacillus plantarum B1765 has the potential to produce SCFA, which could be used for various health benefits.

The Baseline Serum Lipid Levels and Outcomes of NSCLC Patients Receiving Immunotherapy Combined or Non-Combined with Radiotherapy: A Single Center Retrospective Study

In recent years, many studies have shown that lipids and lipid-like substances are key regulatory factors in tumor development and play an important role in immune regulation. However, it remains unclear whether serum lipids influence the outcome of immunotherapy. Therefore, determining the serum lipid levels of the immune treatment-beneficiary population may be valuable. The aim of this study is to evaluate the prognostic value of baseline serum lipid levels in non-small cell lung cancer (NSCLC) patients receiving immunotherapy. We retrospectively included 294 patients with stage III-IV NSCLC who received immunotherapy continuously from December 2018 to November 2021 at our hospital, collecting their pre-treatment lipid levels, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Of these, 160 receiving immunotherapy without combined radiotherapy (ICIs-nRT) and 134 combined with radiotherapy (iRT). The endpoint was the correlation between pre-treatment serum lipid levels and overall survival (OS), as well as progression-free survival (PFS). The X-tile tool was used to determine the optimal cut-off value of the indicators. The Kaplan-Meier survival curves were used to calculate OS and PFS and log rank tests were used for comparison. And the Cox proportional hazard model were used for univariate and multivariate analysis. In all 294 patients, low TG, low TC, and low HDL-C predicted poor OS (P<0.001) and poor PFS (P<0.05). Low LDL-C was associated with poor OS (P = 0.0001). Among 160 patients receiving ICIs-nRT and 134 iRT patients, low levels of TG (P = 0.0134, 0.0024), TC (P = 0.0003, 0.0023), HDL-C (P = 0.0004, 0.0043), and LDL-C (P = 0.0003, 0.0419) were associated with worse OS compared to high levels of them. In the ICIs-nRT patients, low HDL-C predicted poor PFS (P = 0.0011). In 134 iRT patients, low levels of TG (P = 0.0017), TC (P = 0.0028), and LDL-C (P = 0.0330) were poor prognostic factors for PFS. In the univariate and multivariate analysis with OS in all patients, TG and HDL-C were independent risk factors, while TG was an independent risk factor in the analysis with PFS. In ICIs-nRT patients, HDL-C was an independent prognostic factor for patients' OS and PFS. In iRT patients, both TG and HDL-C were prognostic risk factors for OS. These data confirm that higher serum lipid levels are associated with better outcomes in patients with NSCLC undergoing immunotherapy. Serum lipids may identify tumors that are more likely to respond to immunotherapy. Radiation therapy may affect lipid metabolism within the body to enhance the efficacy of immunotherapy.

Transcriptional Knock-down of mstn Encoding Myostatin Improves Muscle Quality of Nile Tilapia (Oreochromis niloticus)

Myostatin (encoded by mstn) negatively regulates skeletal muscle mass and affects lipid metabolism. To explore the regulatory effects of mstn on muscle development and lipid metabolism in Nile tilapia (Oreochromis niloticus), we used antisense RNA to transcriptionally knock-down mstn. At 180 days, the body weight and body length were significantly higher in the mstn-knock-down group than in the control group (p < 0.05). Additionally, fish with mstn-knock-down exhibited myofiber hyperplasia but not hypertrophy. Oil red O staining revealed a remarkable increase in the area of lipid droplets in muscle in the mstn-knockdown group (p < 0.05). Nutrient composition analyses of muscle tissue showed that the crude fat content was significantly increased in the mstn-knock-down group (p < 0.05). The contents of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids were all significantly increased in the mstn-knock-down group (p < 0.05). Comparative transcriptome analyses revealed 2420 significant differentially expressed genes between the mstn-knock-down group and the control group. KEGG analysis indicates that disruptions to fatty acid degradation, glycerolipid metabolism, and the PPAR signaling pathway affect muscle development and lipid metabolism in mstn-knock-down Nile tilapia: acaa2, eci1, and lepr were remarkably up-regulated, and acadvl, lpl, foxo3, myod1, myog, and myf5 were significantly down-regulated (p < 0.05). These results show that knock-down of mstn results in abnormal lipid metabolism, acceleration of skeletal muscle development, and increased adipogenesis and weight gain in Nile tilapia.

Analysis of Fecal Microbiota in Patients with Hypertension Complicated with Ischemic Stroke.

Ischemic stroke is a disease with a very high incidence in the clinic, and hypertension is the most important variable risk factor of ischemic stroke. Studies have shown that intestinal microbes are involved in the occurrence and development of various diseases. This study aims to explore whether intestinal microbes play an important role in the pathogenesis of ischemic stroke in a hypertensive population. In this study, the inpatients in the Department of Neurology and Cardiology of the Second Affiliated Hospital of Shandong First Medical University in April 2021 were selected, including seven patients with hypertension complicated with ischemic stroke and only seven patients with hypertension. After collecting the stool samples of patients, the gene sequence of the samples was detected by 16S rRNA sequencing technology, and the double-ended 2 × 150bp sequencing was carried out. After sequencing, the results were analyzed by diversity analysis, species difference analysis, species function difference analysis, and other bioinformatics tests. According to the test results, serum proteomics and biochemical blood tests were carried out to verify. There was no significant difference in α diversity and β diversity between hypertension complicated with the cerebral infarction and hypertension groups. LEfSe analysis showed that at the genus level, compared with the hypertension group, Bacteroides, UCG_009, and Eisenbergiella had significantly increased relative abundance. The genera with relatively significantly reduced abundance are Ruminococcus_gnavus_group, Sutterellaceae, Burkholderia, and Prevotella and the LDA score of Prevotella is < - 4, which indicates that there are significant differences. Compared with the blood biochemical indexes, the results showed that the level of APOA1 in hypertensive patients with ischemic stroke was significantly higher than that in hypertensive patients (p < 0.05), but there was no significant difference in total cholesterol (CHOL), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein B (APOB), and free fatty acid (NEFA). Proteomic analysis showed that there were 89 up-regulated genes and 51 down-regulated genes in the serum of the two groups, and the expression of APOC2 and APOC3 in the cerebral infarction group with hypertension was significantly higher than that in the hypertension group (p < 0.05). The intestinal diversity of patients with hypertension complicated with stroke is similar to that of patients with hypertension, but there are differences in microbiota, among which Prevotella is the most significant. Prevotella could affect lipid metabolism so that APOC2 and APOC3 in the blood are significantly increased, leading to cerebral artery atherosclerosis and, finally, ischemic stroke. This provides a new idea for preventing and treating ischemic stroke in patients with hypertension, but the mechanism of Prevotella acting on apolipoprotein needs further verification by basic medical research.

Analyzing the impact and mechanism of bisphenol A on testicular lipid metabolism in Gobiocypris rarus through integrated lipidomics and transcriptomics

Bisphenol A (BPA) is one of the most common environmental endocrine chemicals, known for its estrogenic effects that can interfere with male spermatogenesis. Lipids play crucial roles in sperm production, capacitation, and motility as important components of the sperm plasma membrane. However, limited research has explored whether BPA affects lipid metabolism in the testes of male fish and subsequently impacts spermatogenesis. In this study, we employed Gobiocypris rarus rare minnow as a research model and exposed them to environmentally relevant concentrations of BPA (15 μg/L) for 5 weeks. We assessed sperm morphology and function and analyzed changes in testicular lipid composition and transcriptomics. The results demonstrated a significant increase in the sperm head membrane damage rate, along with reduced sperm motility and fertilization ability due to BPA exposure. Lipidomics analysis revealed that BPA increased the content of 11 lipids while decreasing the content of 6 lipids in the testes, particularly within glycerophospholipids, glycerolipids, and sphingolipid subclasses. Transcriptomics results indicated significant up-regulation in pathways such as cholesterol metabolism, peroxisome proliferator-activated receptor signaling, and fat digestion and absorption, with significant alterations in key genes related to lipid metabolism, including apolipoprotein A-I, apolipoprotein C-I, and translocator protein. These findings suggest that BPA exposure can induce testicular lipid metabolism disruption in rare minnows, potentially resulting in abnormalities in rare minnow spermatogenesis.