Expression Of LPL Research Articles

Ozone-Induced Lung Injury are Mediated Via PPAR-Mediated Ferroptosis in Mice.

In recent years, the concentration of PM2.5 in China has decreased, while the concentration of ozone remains rising. Exposure to ozone contributes to respiratory illnesses; however, little is known about the underlying molecular mechanisms. The present study established an ozone-induced lung injury mice model to investigate potential molecular biomarkers and toxic mechanisms. Collected and analyzed the ozone pollution data in Xinxiang city from 2015 to 2022. At the same time, 24 male C57BL/6 mice were randomly assigned to control group and ozone exposure group. The ozone exposure concentration is 1ppm, with 4h of daily exposure for 33 consecutive days. HE staining was used to assess lung histological alterations and lung injury. High-throughput sequencing performed on the lung tissues of mice was used to analyze the differential expressed genes and signal transduction pathways. Xinxiang city is suffering from ozone pollution, especially in summer. HE staining showed that the ozone exposure could induce obvious inflammatory cell infiltration, alveolar wall thickening, or fracture. Transcriptome data revealed that there is a 145 differentially expressed genes between two groups and the genes enriched in PPAR signaling pathway, ferroptosis. The pivotal genes in the PPAR pathway including Adipoq, Lpl, Pck1, and Plin1 expression were significantly reduced. Additionally, the expression of Acsl6 and Scl7a11, which are close to PPAR pathway and ferroptosis has decreased. Ozone exposure could disrupt the lipid metabolism balance via downregulating lipid peroxidation-related genes through the PPAR signaling pathway, which further induced lung cell ferroptosis and aggravated lung injury in mice.

The molecular regulated mechanism of METTL3 and FTO in lipid metabolism of Hu sheep

BackgroundBalanced lipid metabolism can improve the growth performance and meat quality of livestock. The m6A methylation-related genes METTL3 and FTO play important roles in animal lipid metabolism; however, the mechanism through which they regulate lipid metabolism in sheep is unclear. ResultsWe established lipid deposition models of hepatocytes and preadipocytes in Hu sheep. In the hepatocyte lipid deposition model, the genes expression levels of FABP4, Accα, ATGL and METTL3, METTL14, and FTO—were significantly up-regulated after lipid deposition (P < 0.05). Transcriptomic and metabolomic analyses showed that lipid deposition had a significant effect on MAPK, steroid biosynthesis, and glycerophospholipid metabolism pathway in hepatocytes. The m6A methylation level decreased but the difference was not significant after METTL3 interference, and the expression levels of FABP4 and ATGL increased significantly (P < 0.05); the m6A methylation level significantly increased following METTL3 overexpression, and LPL and ATGL expression levels significantly decreased (P < 0.05), indicating that overexpression of METTL3 inhibited the expression of lipid deposition-related genes in a m6A-dependent manner. The m6A methylation level was significantly increased, ATGL expression was significantly decreased (P < 0.05), and LPL, FABP4, and Accα expression was not significantly changed following FTO interference (P > 0.05); the m6A methylation level was significantly decreased after FTO overexpression, and LPL, FABP4, and ATGL expression was significantly increased (P < 0.05), indicating that FTO overexpression increased the expression of lipid deposition-related genes in a m6A-dependent manner. Transcriptomic and metabolomic analyses showed that m6A methylation modification mainly regulated lipid metabolism through triglyceride metabolism, adipocytokine signaling, MAPK signaling, and fat digestion and absorption in hepatocytes. In the lipid deposition model of preadipocytes, the regulation of gene expression is the same as that in hepatocytes. ConclusionsMETTL3 significantly inhibited the expression of lipid deposition-related genes, whereas FTO overexpression promoted lipid deposition. Our study provides a theoretical basis and reference for accurately regulating animal lipid deposition by mastering METTL3 and FTO genes to promote high-quality animal husbandry.

PSVII-19 Effects of silage particle size on beef quality and muscle lipogenesis of finishing Nellore heifers

Abstract The objective of this study was to evaluate the effect of corn silage particle size on beef quality and expression of gluconeogenic and lipogenic genes in feedlot-finished Nellore heifers. Nellore heifers (n = 94), with an initial body weight (BW) of 249.71 ± 34.62, were allotted into 32 pens (three animals per pen) in a completely randomized design, with 2 treatments and 16 repetitions. The treatments were corn silage with a particle size of 13 mm (short) or 24 mm (long). The feeding period lasted 101 d, with the first 15 d for diet adaptation. After slaughter, samples of the longissimus thoracis muscle (LT) from the left side of the half carcass and liver were taken for beef quality and gene expression analyses. The chemical composition of the beef was analyzed using near infrared according to the AOAC method 2007-04, using the FoodScanTM equipment (AOAC method: 2007-04; FOSS, Hillerod, Denmark). RT-qPCR analyses of each gene investigated were carried out using cDNA from 16 biological replicates per treatment (1 heifer chosen randomly in each pen), with each biological replicate subjected to 2 technical replicates. Relative gene expression analyses were calculated using the delta delta ct method and the reference genes used were ACTB and GAPDH. The normality of all experimental data was checked using the Shapiro-Wilk test in SAS software. When the data did not present a normal distribution, transformation was performed using PROC RANK. The model included particle size as a fixed effect and pen as a random effect. There was no treatment effect on collagen, moisture, and mineral content (P &amp;gt; 0.10), but muscles from heifers fed short particle sizes tended to have greater protein content (23.3 versus 22.9; P = 0.098), while muscles from heifers fed with long particles had greater intramuscular fat content (2.62 versus 3.28; P = 0.05). For liver gene expression, heifers fed short particle sizes tended to have greater expression of the PC gene (1.00 versus 0.82; P = 0.06), while PEPCK2 had higher expression in heifers fed long particles (1.00 versus 1.18; P = 0.04). In addition, the long particle size of corn silage affected the expression of PPARA (P = 0.001), and there was no effect of diets (P &amp;gt; 0.05) on PPARG and SREBF1 expressions (Table 1). Expression of LPL, FABP4, SCD1, CPT2 (P &amp;lt; 0.001), and ACACA (P = 0.017) genes increased in the muscle of heifers fed long particle size. Therefore, it is concluded that the use of corn silage with long particle size in feedlot diets has the potential to increase the expression of genes involved in lipogenesis and then increase intramuscular fat in Nellore heifers.

Perioperative systemic IL-6 and immune-adipose- metabolism transcription in tumour and tumour adjacent breast cancer.

Surgical resection is the primary treatment approach for patients with breast cancer. Despite optimal multimodal treatment, metastatic recurrence remains a risk. Surgery-mediated systemic inflammation and local tissue inflammation generate an immunosuppressive and wound-healing environment that may accelerate cancer recurrence and metastasis post-operatively. Investigating the impact of surgery on local and systemic inflammation may provide knowledge for improvement of patient prognosis and treatment opportunities. Systemic cytokines were quantified in the blood plasma of patients with breast cancer pre-operatively, early post-operatively, and late post-operatively. Early post-operative levels of IL-6 were significantly elevated in patients who underwent mastectomy compared with wide local excision. Post-operative IL-6 levels correlate with clinicopathological features (age and BMI). The transcriptomes of local matched tumour and normal tumour adjacent (normal) breast tissue, from patients with breast cancer, were analysed by RNA-Seq. Elevated gene expressions of IL6, ADIPOQ, FABP4, LPL, PPARG, and CD36 in normal tissue were associated with worse overall survival of patients with ER-positive breast cancer. In tissue with higher expression of IL6 and ADIPOQ, a higher abundance of M2-like macrophage gene expression was identified. This study revealed perioperative systemic dynamics of inflammatory mediators and identified local immune-adipose-metabolism gene expression in tumour-adjacent tissue associated with pro-tumour function.

Prehatch thermal manipulation of embryos and posthatch baicalein supplementation increased liver metabolism, and muscle proliferation in broiler chickens

The exposure of broiler chickens to high ambient temperatures causes heat stress (HS), negatively affecting their health and production performance. To mitigate heat stress in broilers, various strategies, including dietary, managerial, and genetic interventions, have been extensively tested with varying degrees of efficacy. For sustainable broiler production, it is imperative to develop an innovative approach that effectively mitigates the adverse effects of HS. Our previous studies have provided valuable insights into the effects of prehatch embryonic thermal manipulation (TM) and posthatch baicalein supplementation on embryonic thermotolerance, metabolism, and posthatch growth performance. This follow-up study investigated the effect of these interventions on gluconeogenesis and lipid metabolism in the liver, as well as muscle proliferation and regeneration capacity in heat-stressed broiler chickens. A total of six-hundred fertile Cobb 500 eggs were incubated for 21 d. After candling, 238 eggs were subjected to TM at 38.5°C with 55% relative humidity (RH) from embryonic day (ED) 12 to 18. These eggs were transferred to the hatcher and kept at a standard temperature (37.5°C) from ED 19 to 21, while 236 eggs were incubated at a controlled temperature (37.5°C) till hatch. After hatching, 180 day-old chicks from both groups were raised in 36 pens treatment (n = 10 birds/pen, 6 replicates per treatment). The treatments were: 1) Control, 2) TM, 3) Control heat stress (CHS), 4) Thermal manipulation heat stress (TMHS), 5) Control heat stress supplement (CHSS), and 6) Thermal manipulation heat stress supplement (TMHSS). Baicalein was added to the treatment group diets starting from d 1. All birds were raised under the standard environment for 21 d, followed by chronic heat stress from d 22 to 35 (32-33 ⁰C for 8 h) in the CHS, TMHS, CHSS, and TMHSS groups. A thermoneutral (22-24⁰C) environment was maintained in the Control and TM groups. RH was constant (50 ± 5%) throughout the trial. In the liver, TM significantly increased (P < 0.05) IGF2 expression. Baicalein supplementation significantly increased (P < 0.05) HSF3, HSP70, SOD1, SOD2, TXN, PRARα, and GHR expression. Moreover, the combination of TM and baicalein supplementation significantly increased (P < 0.05) the expression of HSPH1, HSPB1, HSP90, LPL, and GHR. In the muscle, TM significantly increased (P < 0.05) HSF3 and Myf5 gene expression. TM and baicalein supplementation significantly increased (P < 0.05) the expression of MyoG and significantly (P < 0.05) decreased mTOR and PAX7. In conclusion, the prehatch TM of embryos and posthatch baicalein supplementation mitigated the deleterious effects of HS on broiler chickens by upregulating genes related to liver gluconeogenesis, lipid metabolism, and muscle proliferation.

Screening of the Lipid-Lowering Probiotic Lactiplantibacillus Plantarum SDJ09 and its Anti-Obesity Mechanism.

In this study, 39 strains of lactic acid bacteria were screened from several fermented foods. Based on the evaluation of functional and prebiotic properties, Lactiplantibacillus plantarum SDJ09 was selected as a promising candidate. It gave a 48.16% cholesterol reduction and 33.73% pancreatic lipase inhibition in cells; exhibited high resistance to acid, bile salts, and gastrointestinal fluid; and had strong antibacterial activity and high adhesion capabilities. More importantly, the lipid-lowering effect of L. plantarum SDJ09 was also investigated using 3T3-L1 mature adipocytes and HepG2 nonalcoholic fatty liver disease models. L. plantarum SDJ09 effectively decreased triglyceride accumulation by more than 50% in both cell models, in which the expression of PPARγ, C/EBPα, aP2, and LPL in 3T3-L1 cells was significantly downregulated by L. plantarum SDJ09. L. plantarum SDJ09 also improved lipid metabolism by downregulating the expression of HMGCR, SREBP-1c, ACC, and FAS and upregulating the expression of CYP7A1 in HepG2 nonalcoholic steatohepatitis cells. Therefore, L. plantarum SDJ09 has the potential to effectively decrease obesity and non-alcoholic fatty liver disease (NAFLD) by inhibiting lipid accumulation, providing a prospective probiotic agent for anti-obesity.

Sargassum horneri extract fermented by Lactiplantibacillus pentosus SH803 mediates adipocyte metabolism in 3T3-L1 preadipocytes by regulating oxidative damage and inflammation

Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H2O2-induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1β, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPβ, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPβ, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems.

Maternal High Fat Diet and its Expressions in the Heart and Liver in the Mice Embryogenesis.

The developmental biology for the nonalcoholic fatty liver disease and coronary heart disease are known but elaborative ideas of triglycerides phenomenon in the embryo-genesis of the liver and the heart are still not clear. The aim of the study was to relate different triglycerides like LXRα, LPL, LDL R, PPARG-, SREBP-1C expression in the high fat fed mice with the normal fed diet mice in the process of developmental and embryo-genesis biology. Tissue preparation was done by ripalysis. Different protein content was obtained via western blot for the 6 samples namely a-17.5 days mice embryo heart; b- 0th day or the birthday mice infant heart; c-1 week mice infant heart; d-2 weeks mice infant heart; e-3 weeks mice infant heart; f-Adult mice heart. Protein lysates from the heart tissues of the mice was obtained via homegenization and centrifugation. Hematoxylin and Eosin (H and E) was done to see the fat droplets in the liver tissues at the different developmental stages. LXRα,SREBP-1C expression in 17.5 days mice embryo heart and 0th day or the birthday mice infant heart is highly expressed in the high fat diet. LDL-R in the high fat diet mice is increased in 2 weeks mice infant heart but in17.5 days mice embryo heart and in 0th day or the birthday mice infant heart it is low expression but from 1week mice infant heart to the adult mice heart the expression is in decreasing trend. Similarly LPL is highly expressed in17.5 days mice embryo heart and 1 week mice infant heart and thus low expression in decreasing order until adult mice heart.Thus, these results collectively shows that maternal HF diet increases expression of proteins such as LPL, LDLr in the embryo phase and thus getting normal expressions in the adult phase that facilitate Triglycerides (TAG) hydrolysis across the liver and the heart. Also,maternal high fat diet increases the SREBP1c expression, leading to stimulation of LPL Expression. In summary, using a pregnant mice model, we found that maternal high fat diet increases the fetal fat accumulation. Elevated placental LPL activity and expression of genes that facilitate placental lipid transport suggest that enhanced placental lipid transport may play a key role in maternal nutrition and obesity-induced fetal fat accumulation.

Regional adiposity and insulin sensitivity - interactions with menopause and HIV in middle-aged Black African women.

To explore depot-specific functional aspects of adipose tissue, examining the putative role for menopause and HIV status on insulin sensitivity (SI) and beta-cell function in Black South African women. Women (n = 92) from the Middle-Aged Soweto Cohort, including premenopausal HIV-negative (n = 21); premenopausal women living with HIV (WLWH; n = 11); postmenopausal HIV-negative (n = 42); postmenopausal WLWH (n = 18) underwent the following tests: body composition (dual energy x-ray absorptiometry); fasting bloods for sex hormones, inflammation and adipokines; frequently sampled intravenous glucose tolerance test for SI and beta-cell function (disposition index, DI); abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) biopsies for cell size and mRNA expression of adipokines, inflammation, and estrogen receptors [ER]. Depot-specific associations between gene expression and insulin parameters did not differ by HIV or menopause status. Pooled analysis showed significant models for SI (P = 0.002) and DI (P = 0.003). Higher SI was associated with lower leptin and CD11c expression in aSAT and higher adiponectin in gSAT. Higher DI was associated with higher aSAT and gSAT expression of adiponectin, LPL, ERα, and PPARγ, and lower leptin in aSAT. WLWH had higher expression of adiponectin and lower expression of leptin in both aSAT (P = 0.002 and P = 0.005) and gSAT (P = 0.004 and P = 0.002), respectively, and a larger proportion of smaller cells in aSAT (P < 0.001). Insulin sensitivity and beta cell function were distinctively associated with aSAT and gSAT. While menopause did not influence these relationships, HIV had a significant effect on adipose tissue, characterised by variations in cell size distribution and transcript levels within the depots.

Effects of emulsifiers on lipid metabolism and performance of yellow-feathered broilers

BackgroundReducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed.ResultsThe results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P < 0.05), and the half-even-chamber rate was significantly increased (P < 0.05); (2) The mRNA expression levels of Cd36, Dgat2, Apob, Fatp4, Fabp2, and Mttp in the small intestine were significantly increased (P < 0.05). (3) Furthermore, liver TG content significantly decreased (P < 0.05), and the mRNA expression level of Fasn in liver was significantly decreased (P < 0.05), while the expression of Apob, Lpl, Cpt-1, and Pparα significantly increased (P < 0.05). (4) The mRNA expression levels of Lpl and Fatp4 in adipose tissue were significantly increased (P < 0.05), while the expression of Atgl was significantly decreased (P < 0.05). (5) Compared with the reduced oil diet group, the half-evading rate and abdominal fat rate of broilers in the reduced oil diet + 500 mg/kg emulsifier group were significantly increased (P < 0.05), and the serum level of LDL-C increased significantly (P < 0.05)0.6) The mRNA expression levels of Cd36, Fatp4, Dgat2, Apob, and Mttp in the small intestine were significantly increased (P < 0.05). 7) The mRNA expression levels of Fasn and Acc were significantly decreased in the liver (P < 0.05), while the mRNA expression levels of Lpin1, Dgat2, Apob, Lpl, Cpt-1, and Pparα were significantly increased (P < 0.05).ConclusionsThese results suggest that dietary emulsifier can enhance the fat utilization efficiency of broilers by increasing the small intestinal fatty acid uptake capacity, inhibiting hepatic fatty acid synthesis and promoting hepatic TG synthesis and transport capacity. This study provides valuable insights for the potential use of emulsifier supplementation to improve the performance of broiler chickens.

Identification of Genes Crucial for Biological Processes in Breast Cancer Liver Metastasis Relapse.

Breast cancer, when advancing to a metastatic stage, involves the liver, impacting over 50% of cases and significantly diminishing survival rates. Presently, a lack of tailored therapeutic protocols for breast cancer liver metastasis (BCLM) underscores the need for a deeper understanding of molecular patterns governing this complication. Therefore, by analyzing differentially expressed genes (DEGs) between primary breast tumors and BCLM lesions, we aimed to shed light on the diversities of this process. This research investigated breast cancer liver metastasis relapse by employing a comprehensive approach that integrated data filtering, gene ontology and KEGG pathway analysis, overall survival analysis, identification of the alteration in the DEGs, visualization of the protein-protein interaction network, Signor 2.0, identification of positively correlated genes, immune cell infiltration analysis, genetic alternation analysis, copy number variant analysis, gene-to-mRNA interaction, transcription factor analysis, molecular docking, and identification of potential treatment targets. This study's integrative approach unveiled metabolic reprogramming, suggesting altered PCK1 and LPL expression as key in breast cancer metastasis recurrence.

Effects of Corbicula fluminea meal in high-fat diet on growth, lipid metabolism and intestinal microbiota of juvenile rice field eel Monopterus albus

Corbicula fluminea meal was added to a high-fat diet for eight weeks to determine its effects on growth, lipid metabolism, and intestinal microbiota in juvenile rice field eel (Monopterus albus). C. fluminea meal was made of dried and crushed soft parts of freshwater clam. The study included four diets: a normal fat diet (6.63% lipid, CON), a high fat diet (12.61% lipid, HFD), and a high fat diet supplemented with 1% or 2% C. fluminea meal (CFM1 and CFM2, respectively). The results showed that: (1) the growth performance was higher in the HFD, CFM1 and CFM2 group compared with the CON group, the hepatosomatic index (HSI) was significantly higher in fish fed the high-fat diet than in those fed other diets. (2) Compared with the CON group, The levels of serum triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) contents, glutamate pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) activities and the number of hepatic lipid droplets were significantly increased in the HFD group. The addition of C. fluminea meal both reduced liver damage and fat deposition. (3) The mRNA expressions of pparγ, fas, acc, me1, srebp1, g6pdh, hsl, lpl, cpt1, and cpt2 in the HFD group were significantly upregulated, while HFD supplemented with C. fluminea meal significantly downregulated the mRNA expressions of pparγ, fas, acc, me1, srebp1 and g6pdh and significantly upregulated the mRNA expressions of hsl and lpl. (4) The alpha diversity of intestinal microbial community in the HFD group was higher than those in the CON and CFM1 groups. The beta diversity revealed the microbial composition differed in the HFD group from the CON and CFM1 groups. The abundance of Firmicutes in the HFD group increased significantly compared with the CON and CFM1 groups, while the abundances of Cetobacterium decreased. In conclusion, the high-fat diet resulted in abnormal liver fat deposits and intestinal microbiota dysfunction in M. albus, but HFD supplemented with 1% or 2% C. fluminea meal reduced these negative effects.

Arthrospira platensis F&M-C265 reduces cardiometabolic risk factors in rats fed a high fat diet

Clinical studies indicate that Arthrospira platensis (A. platensis) mitigates cardiometabolic risk factors, but the underlying mechanisms are very elusive. To fill this gap, Sprague-Dowley rats were fed either AIN-76 normal diet (5 % corn oil) or high-fat (HF; 30 % lard + 3 % corn oil) or HF + 5 % A. platensis F&M-C256 diet for 3 months. A. platensis F&M-C256 decreased blood triglycerides and total cholesterol, systolic and diastolic pressure and enhanced the expression of thermogenesis-related genes Prdm16, Dio2, PPARγ, Ucp1 and Lpl in visceral adipose tissue, compared to HF-diet. A. platensis reduced ANGPTL3 plasma levels and hepatic steatosis, prevented periaortic adipose tissue hypertrophy and increased aortic eNOS expression. These data provide some mechanistic evidence about the beneficial effects of A. platensis observed in human studies. Further controlled trials are needed to verify the clinical usefulness of A. platensis supplementation against metabolic disorders, to select the dosing regimens and the subgroup of patients with likelihood of benefit.

The potential efficacy of Artemisia anuua L. extract nanoparticles in mitigating obesity-related-metabolic complications in hypercaloric diet-fed rats

ABSTRACT Obesity-related health problems are worsening in various societies worldwide. Artemisia anuua L. (AA) has distinctive health benefits, including anti-inflammatory, antioxidant, and insulin-sensitizing properties. Nanoformulation of herbal extracts is a new approach to enhance the bioavailability of natural products. This study aimed to evaluate the efficacy of AA extract, either the conventional extract (AAE) or its nano-form (AAEN), in modulating obesity-related metabolic complications in hypercaloric (high-fat/high-sucrose) diet-induced obese rats. Forty-eight rats were divided into two groups fed either a basal or hypercaloric diet for twelve weeks. Starting from the eighth week, each main group was subdivided into three subgroups and treated orally with either saline, AAE, or AAEN until the end of the experiment. Both AAE and AAEN exerted antiadipogenic effects. They reduced body weight and epididymal fat, mitigated dyslipidemia, improved glucose utilization and insulin resistance, reduced hyperleptinemia, increased serum adiponectin, and decreased oxidative stress and inflammatory markers. These results were mediated by regulating SIRT-1, PGC-1α, SREBP-1, PPAR-γ, FAS, LPL, IRS 1, and GLUT4 gene expression, suggesting an effect of AA on de novo lipogenesis and glucose utilization. The AAEN produced more expressive ameliorating effects than the conventional extract. AAE administration ameliorated the obesity-associated metabolic complications induced by feeding a hypercaloric diet, implying that this extract may be used as a complementary treatment option for obesity and its metabolic consequences. The antiadipogenic effectiveness of AAE was enhanced by its nanoformulation, suggesting that the nanoparticle system can be applied to boost other herbal medicine effectiveness.

Identification of key pathways and mRNAs in interstitial cystitis/bladder pain syndrome treatment with quercetin through bioinformatics analysis of mRNA-sequence data.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. QCT treatment significantly decreased the level of MPO, IL-1β, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1β, IL-6 and TNF-α. In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.

Dietary Bacillus species modulate lipid metabolism-related parameters, growth, water quality, and bacterial load in Nile tilapia (Oreochromis niloticus )

This study examined the impact of supplementing Bacillus spp. mixtures at concentrations of 0.2 g/kg (PRO-0.2) and 0.5 g/kg (PRO-0.5) on Nile tilapia (Oreochromis niloticus) for 90 days. Fish groups receiving PRO-0.2 and PRO-0.5 exhibited significantly lower water ammonia levels than the control group, in linear and quadratic patterns. Furthermore, their length and weight increased exponentially over time, peaking at the end of the experiment. After 90 days, the PRO-0.5 group displayed the highest mean weight gain. Additionally, both the PRO-0.2 and PRO-0.5 groups had the lowest food conversion ratios and highest protein efficiency ratios in a linear pattern. They also showed improved liver function, as indicated by lower levels of liver enzyme (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) compared to the control group. In terms of the lipid profile, the PRO-0.2 and PRO-0.5 groups had significantly lower serum levels of low-density lipoprotein, triglycerides, in linear and quadratic patterns, and cholesterol compared to the control group, with no significant differences in cholesterol levels. High-density lipoprotein increased significantly in both PRO-0.2 and PRO-0.5 groups after 90 days, following a linear pattern. Hepatic alkaline phosphatase levels decreased in both the PRO-0.2 and PRO-0.5 groups, following a significant linear pattern over time. After 30 days, the expression of hepatic fatty acid binding protein 3 (fabp3) significantly decreased in the PRO-0.5 group. Intestinal cluster of differentiation 36 (cd36) and fabp3 expression markedly increased, with cd36 showing the greatest rise. After 90 days, hepatic cd36 expression became prominent in both PRO-0.2 and PRO-0.5 groups. Expression of fas was significantly downregulated in both the PRO-0.2 and PRO-0.5 groups. Notably, hepatic lipoprotein lipase (lpl) expression significantly increased in the supplementation groups after 30 days but decreased significantly after 90 days. Overall, this study highlights the positive impact of dietary mixtures of Bacillus spp. on various aspects, including water quality, growth performance, feed utilization, survivability, expression of lipid metabolism-related genes, lipid profile, body composition, and bacterial load in both water and fish bodies.

Exploring the mechanism of allicin in lowering blood lipids based on the CSE/H2S pathway

This study aims to elucidate the mechanism by which allicin modulates lipid metabolism in HFD (High-Fat Diet) mice through the CSE/H2S pathway. Allicin intervention (120 mg/kg) significantly reduced mouse body weight and serum total cholesterol (TC) and triglyceride (TG) levels (p < 0.05), while enhancing hepatic antioxidant levels (p < 0.05). Transcriptomic analysis of the liver indicated that allicin influenced several key metabolic pathways, including lipid metabolism (steroid hormone synthesis, unsaturated fatty acid synthesis, and PPAR signaling pathways) and antioxidant pathways (chemical carcinogenesis-reactive oxygen species pathway and glutathione metabolism pathways). RT-qPCR experiments confirmed that in the HA group (the high dose allicin, 120 mg/kg), the expression level of CD36 in the liver was downregulated, while the expression of LPL, GST, GPX, and GCLC were upregulated. Furthermore, the metabonomic analysis identified core differential metabolites primarily associated with sulfate/sulfite metabolism and glutathione metabolism pathway. This was evidenced by alterations in the levels of sulfur-containing compounds, such as H2S, l-Glutathione (reduced), G-glutamylcysteine, and methionine. In the constructed HepG2 high-fat cell model, dl-Propargylglycine (PAG, H2S synthesis inhibitor) treatment resulted in significantly higher lipid content compared to the Allicin-600 group, and expression levels of antioxidant genes like GST, GPX, and GCLC are reduced. This further validates the pivotal role of the CSE/H2S pathway in allicin's lipid-lowering effects. In summary, allicin demonstrates potent lipid-lowering activity when serving as an H2S donor, setting the stage for the development of a broader range of allicin-related health products.

Genome-Wide Search Links Senescence-Associated Secretory Proteins With Susceptibility for Coronary Artery Disease in Mouse and Human.

Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associated secretory phenotype (SASP). How SASP contributes to atherosclerosis and CAD, however, remains unclear. Here, we integrated RNA-array datasets of senescent human coronary arterial endothelial cells (HCAECs) and aortic smooth muscle cells (HASMCs) as well as genome-wide association data for CAD. We identified 26 genes from HCAECs and 6 genes from HASMCs related to SASP and CAD in both in-house and published datasets. Of which, Cystatin C (CST3), a CAD susceptibility gene, was found to be expressed in both HCAECs and HASMCs, thus, it was prioritized for further investigation. We demonstrated it was significantly elevated in senescent vascular cells, aged arteries, and early atherosclerosis. In vitro experiments showed that CST3 enhances the monocyte-endothelial cell adhesion. Additionally, ligand-receptor pairing analyses revealed two important pathways, COL4A1-ITGA1 and LPL-LRP1 pathways, linked to the critical processes in the development of atherosclerosis, including cell adhesion, inflammation response, extracellular matrix organization, and lipid metabolism. We further demonstrated a reduced monocyte-endothelial cell adhesion following the knockdown of COL4A1 or ITGA1 and a significantly increased expression of COL4A1, ITGA1, and LPL in arterial intima of aged mice and ApoE-/- mice. Our findings demonstrate that vascular cell-derived SASP proteins increase the CAD susceptibility and identify CST3 functionally contributing to atherosclerosis.

Methazolamide Can Treat Atherosclerosis by Increasing Immunosuppressive Cells and Decreasing Expressions of Genes Related to Proinflammation, Calcification, and Tissue Remodeling.

It has been reported that carbonic anhydrase I (CA1) is a target for the diagnosis and therapy of atherosclerosis (AS) since CA1 can promote AS aortic calcification. We also found that methazolamide (MTZ), a drug for glaucoma treatment and an inhibitor of carbonic anhydrases, can treat AS by inhibiting calcification in aortic tissues. This study focused on the therapeutic mechanism of MTZ and the pathogenic mechanism of AS. In this study, a routine AS animal model was established in ApoE-/- mice, which were treated with MTZ. The aortic tissues were analyzed using single-cell sequencing. MTZ significantly increased the proportions of B-1/MZB B cells with high expressions of Nr4A1 and Ccr7, CD8+CD122+ Treg-like cells with high Nr4A1 expression, and smooth muscle cells with high Tpm2 expression. These cells or their marker genes were reported to exert immunosuppressive, anti-proinflammatory, and atheroprotective effects. MTZ also decreased the proportions of endothelial cells with high expressions of Retn, Apoc1, Lcn2, Mt1, Serpina3, Lpl, and Lgals3; nonclassical CD14+CD16++ monocytes with high expressions of Mt1, Tyrobp, Lgals3, and Cxcl2; and Spp1+ macrophages with high expressions of Mmp-12, Trem2, Mt1, Lgals3, Cxcl2, and Lpl. These cells or their marker genes have been reported to promote inflammation, calcification, tissue remodeling, and atherogenesis. A significant decrease in the proportion of CD8+CD183 (CXCR3)+ T cells, the counterpart of murine CD8+CD122+ T cells, was detected in the peripheral blood of newly diagnosed AS patients rather than in that of patients receiving anti-AS treatments. These results suggest that MTZ can treat AS by increasing immunosuppressive cells and decreasing expressions of genes related to inflammation, calcification, and tissue remodeling.

C/EBPα Acts As an RNA Binding Protein Essential for, and Promotes End-Stage Macrophage Differentiation

The transcription factor C/EBPα is a well characterized DNA binding protein with essential functions in controlling and regulating myeloid differentiation and lipid metabolism. Herein, we describe C/EBPα's separate and distinct RNA binding characteristics. Using Chromatin RNA Immunoprecipitation, we identified that C/EBPα interacts primarily with RNA introns in both HL-60 and THP-1 cells, with a preference for a palindromic GC-rich binding motif. Structural prediction in conjunction with RNA electrophoretic mobility shift assays show that C/EBPα interacts with RNA through two previously undescribed domains located towards the proteins N terminus. These domains are distinct from C/EBPα's DNA binding b-ZIP domain which is instead located on the proteins C terminus. Mouse bone marrow transplantation and in vitro cytokine assays reveal that C/EBPα RNA binding appears to be essential for macrophage maturation but not neutrophil differentiation. To better understand these phenotypic differences, we expanded our observations into the transcriptomic space by utilizing single-cell CITE-Seq. In line with biochemical data, notable mature cell populations were absent when the C/EBPα's RNA binding domains are excluded from the protein. Intriguingly, differential gene expression revealed strong, selective upregulation of Lipoprotein Lipase (Lpl) in monocyte, but not neutrophil populations (Panel 1). It has been previously reported that dysregulation of Lpl affects bone marrow monocyte progenitor differentiation and results in dysregulated cellular mobilization from the bone marrow, a phenotype that is commonly seen in cancers such as AML. The increased abundance of monocyte and neutrophil populations in the C/EBPα RNA deletion samples is therefore suggestive that C/EBPα RNA binding is critical in regulating terminal differentiation and mobilization circuits which may become dysregulated or perturbed in diseases such as AML. On-going analyses are investigating the RNA velocity trajectory of captured cell populations in an attempt to better understand at which stage C/EBPα RNA binding becomes essential for terminal maturation and differentiation of select cell populations. Taken together, we demonstrate that C/EBPα is also a bona fida RNA binding protein with unique functions distinct from its DNA binding activity that are essential for monocyte maturation, differentiation and mobilization. Panel 1 - Identified Cell Populations Following scCITE-Seq with C/EBPα Full-Length (WT) and C/EBPα RNA Binding Deletion (DD). Each circle represents a single cell presented in UMAP space. The left panel shows populations identified with the full-length C/EBPα construct. The right panel shows the cell populations identified with the RNA domain deletion construct. Notable differences in cell populations and numbers are evident. Overlayed onto the cells is the expression of Lipoprotein Lipase (Lpl). Expression is shown as a gradient from black up to green, representing a log2(4) expression. Lpl expression is shown to be expressed uniquely in the monocyte population of cells almost exclusively in the RNA deletion sample.