Expression Of Lipid Metabolism Genes Research Articles

Favorable inhibitory effect of clodronate on hepatic steatosis in short bowel syndrome model rats.

This study investigated the anti-inflammatory effect of clodronate, a vesicular nucleotide transporter (VNUT) inhibitor, on intestinal-failure-associated liver disease (IFALD) in a rat model of short bowel syndrome (SBS). The rats underwent jugular vein catheterization for continuous total parenteral nutrition (TPN) and 90% small bowel resection. The animals were divided into the following groups: TPN/SBS (Control group), TPN/SBS/intravenous administration of low-dose clodronate (20mg/kg twice per week; Low group), or TPN/SBS/intravenous administration of high-dose clodronate (60mg/kg twice per week; High group). On day 7, the rats were euthanized. Hepatic steatosis and hepatocellular injury were also assessed. Hepatic steatosis and lobular inflammation in the liver were observed in all groups. The High group showed histologically reduced hepatic steatosis compared with the Control group. IL-6 and Nlrp3 expression in the High group was significantly suppressed compared to that in the Control group. The expression of other inflammatory cytokines tended to be lower in the High dose group than in the control group. The lipid metabolism gene expression in the liver specimens showed no significant differences among the groups. The high-dose administration of clodronate may, therefore, inhibit hepatic steatosis and inflammation associated with IFALD in patients with SBS.

TMET-17. LIPID METABOLIC HETEROGENEITY OF GLIOMA CELLULAR STATES REVEALS ENVIRONMENTAL DEPENDENCIES

Abstract Malignant growth and survival of cancer is supported through reprogrammed lipid metabolism. In gliomas, genetic alterations can drive lipid metabolic dysregulation revealing therapeutic opportunities to exploit lipid metabolic vulnerabilities within genetically defined subsets of glioma tumors. However, it remains unclear whether inter- and intra-tumoral transcriptomic heterogeneity in gliomas relates to distinct lipid programs and potential dependencies. Here we set out to characterize pan-glioma lipid metabolic heterogeneity through genomic, transcriptomic, and lipidomic profiling of a large and diverse cohort of patient tumor samples. We define key axes of lipid metabolic variability across gliomas and identify relationships between lipid metabolic gene expression programs and glioma lipidomic profiles. Intriguingly, intersection of lipid gene expression signatures with single cell RNA sequencing revealed patterns of lipid metabolic heterogeneity that distinguish neurodevelopmental cellular states of gliomas, mirroring patterns of lipid metabolic diversity across cell types within the normal brain. Consequently, tumors with opposing cellular state enrichment have distinct lipid metabolism and environmental dependencies. Tumors enriched for Radial Glia-like states have high capacity for de novo fatty acid synthesis while tumors enriched for oligodendrocyte progenitor-like states are dependent on exogenous sources of lipids for survival and growth. These findings connect inter- and intra-tumoral heterogeneity of cellular states to variability in lipid metabolic reprogramming to reveal future avenues for precision medicine.

Adaptation mechanism of clam Ruditapes philippinarum under polycyclic aromatic hydrocarbon stresses: Accumulation and excretion

Persistent organic pollutants (POPs) are easily accumulated in organisms due to its high lipophilicity. Bivalves are still one of the marine invertebrates with high species diversity despite experiencing with environmental pollution. However, studies investigating the adaptation mechanisms of bivalves towards POPs have been lacking. In this study, we chose benzo[a]pyrene (B[a]P), a typical POPs, to investigate the accumulation and excretion mechanism of clam Ruditapes philippinarum towards B[a]P. Laser confocal microscopy images of ovaries and testes confirmed significant colocalization between lipid droplets and B[a]P. However, B[a]P in the testes might mainly excrete with the excretory fluid. Furthermore, lipidomics results indicated that the upregulated TGs were TGs with 48–58 total carbon atoms and 6–12 double bonds in acyl side chains in ovaries, while the upregulated TGs mainly distributed in 48–58 total carbon atoms and 4–14 double bonds in acyl side chains in testes. In ovaries, gene expression of lipid metabolism and phospholipid metabolism basically presented an upward trend at Pro and Mat stages, while entirely performed a downregulation trend at Gro stage. Testes had the opposite regulation with that. Additionally, B[a]P prompted the excretion ability of female clams, but exhibited a complex effect in the male. This study provides a scientific basis for bivalve toxicology and healthy aquaculture, which is of great significance for marine ecological environment protection and aquatic product safety of China.

Expression of lipid-metabolism genes is correlated with immune microenvironment and predicts prognosis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. This study was aimed to identify a lipid metabolism-related signature associated with the HCC microenvironment to improve the prognostic prediction of HCC patients. Clinical information and expression profile data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, including the GEO dataset GSE76427. The gene expression profile of lipid metabolism was downloaded from Molecular Signatures Database (MSigDB) database. The infiltrating immune cells were estimated by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE), MCP-counter, and TIMER algorithms. Functional analysis, including Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene set enrichment analysis (GSEA) were performed to elucidate the underlying mechanisms. The prognostic risk model was performed by Least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis. Two distinct subgroups of survival were identified. Better prognosis was associated with high immune score, high abundance of immune infiltrating cells, and high immune status. GO and KEGG analysis showed that differentially expressed genes (DEGs) between the two subgroups were mainly enriched in immune related pathways. GSEA analysis suggested that the expression of lipid metabolism related genes (LMRGs) was related to dysregulation of immune in the high-risk group. Risk models and clinical features based on LMRGs predicted HCC prognosis. This study indicated that the lipid metabolism-related signature was important for the prognosis of HCC. The expression of LMRGs was related to the immune microenvironment of HCC patients and could be used to predict the prognosis of HCC.

Evaluation of black soldier fly larvae oil (Hermatia illucens L.) calcium salt as an alternative fat source for laying quail diets.

This study aims to determine the effect of adding saponified black soldier fly larvae oil calcium salt (BSFLO-SCa) to quail feed as an alternative source of fat on laying performance, blood lipid profile, egg quality, and gene expression in lipid metabolism. A total of 120 female Japanese quails (Coturnix japonica) aged 24 weeks were divided into 3 treatments, each with 8 replications, and each replication consisted of 5 quails in a completely randomized design. The applied treatments were the inclusion of basal feed as a control (T0) and basal feed supplemented with 1% BSFLO-SCa (T1) and 2% BSFLO-SCa (T2). The study indicated that the supplementation starting from 1% of BSFLO-SCa significantly decrease (p<0.05) in feed conversion ratio (FCR), blood lipid profile (total cholesterol, LDL-cholesterol). Gene expression on fat synthesis of fatty acid synthase (FAS) and cholesterol synthesis of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) downregulated (p<0.05). In addition, the other parameters did not affect by supplementation of 1% BSFLO-SCa. The inclusion at 2% of BSFLO-SCa significantly increased (p<0.05) protein content of yolk and albumen, egg weight, egg shape index, and gene expression on fat oxidation of carnitine palmitoyltransferase-1 (CPT-1). Egg yolk cholesterol, egg albumen ash, haugh unit (HU), and gene expression on fat synthesis of acetyl-CoA carboxylase (ACC) were significantly reduced (p<0.05). Addition of 2% BSFLO-SCa in the feed improves performance, egg quality, and reduces cholesterol in the blood and eggs of quail. This improvement is accompanied by a reduction in the expression of key genes involved in lipid metabolism. BSFLO-SCa oil has the potential to be an alternative oil source in quail feed.

Acute waterborne cadmium exposure induces liver ferroptosis in Channa argus

The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe2+, ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.

Fatty acid oxidation is critical for the tumorigenic potential and chemoresistance of pancreatic cancer stem cells

BackgroundWe have previously demonstrated the significant reliance of pancreatic Cancer Stem Cells (PaCSCs) on mitochondrial oxidative phosphorylation (OXPHOS), which enables versatile substrate utilization, including fatty acids (FAs). Notably, dysregulated lipid scavenging and aberrant FA metabolism are implicated in PDAC progression.Methods & resultsOur bioinformatics analyses revealed elevated expression of lipid metabolism-related genes in PDAC tissue samples compared to normal tissue samples, which correlated with a stemness signature. Additionally, PaCSCs exhibited heightened expression of diverse lipid metabolism genes and increased lipid droplet accumulation compared to differentiated progenies. Treatment with palmitic, oleic, and linolenic FAs notably augmented the self-renewal and chemotherapy resistance of CD133+ PaCSCs. Conversely, inhibitors of FA uptake, storage and metabolism reduced CSC populations both in vitro and in vivo. Mechanistically, inhibition of FA metabolism suppressed OXPHOS activity, inducing energy depletion and subsequent cell death in PaCSCs. Importantly, combining a FAO inhibitor and Gemcitabine treatment enhanced drug efficacy in vitro and in vivo, effectively diminishing the CSC content and functionality.ConclusionTargeting FAO inhibition represents a promising therapeutic strategy against this highly tumorigenic population.

Effects of cadmium on the growth, muscle composition, digestion, gene expression of antioxidant and lipid metabolism in juvenile tilapia (Oreochromis niloticus)

Cadmium could induce various degrees of harm to aquatic organisms. A 30-day feeding trial was conducted to investigate the effects of cadmium on growth, muscle composition, digestive enzyme activity, gene expression of antioxidants and lipid metabolism in juvenile genetic improvement of farmed tilapia (GIFT, Oreochromis niloticus, Initial weight: 21.36 ± 0.24 g). Four cadmium concentrations of aquaculture water were designed: 0, 0.2, 0.4, and 0.6 mg/L Cd2+. The main results are as follows: Compared with the control group (0 mg/L Cd2+), the weight gain rate (WGR), specific growth rate (SGR), daily growth index (DGI), and spleen index (SI) of juvenile GIFT under cadmium stress were significantly decreased (p&amp;lt; 0.05). The contents of crude protein and crude lipid in muscle were significantly decreased (p&amp;lt; 0.05), and the ash was significantly increased (p&amp;lt; 0.05). The activities of trypsin, lipase, and α-amylase in the intestinal were significantly decreased (p&amp;lt; 0.05). The relative expression levels of carnitine palmityl transferase 1 (cpt-1), peroxisome proliferator-activated receptor α (pparα), pparγ, hormone-sensitive lipase (hsl), lipoprotein lipase (lpl), malate dehydrogenase (mdh), leptin (lep), fatty acid synthetase (fas), cholesterol response element binding protein 1 (srebp1), squalene cyclooxygenase (sqle), and stearoyl-CoA desaturase (scd) genes in liver were significantly decreased (p&amp;lt; 0.05). The relative expression levels of catalase (cat), superoxide dismutase (sod), glutathione S-transferase (gst), and glutathione peroxidase (gsh-px) genes in the liver were significantly decreased (p&amp;lt; 0.05). In conclusion, exposure to cadmium stress could impact growth, muscle composition, digestive enzyme activity, gene expression of antioxidant and lipid metabolism in juvenile GIFT.

Complex actions of sodium glucose transporter-2 inhibitors on lipids, calcific atherosclerosis, and bone density.

Inhibitors of sodium-glucose cotransporter-2 (SGLT2) lower renal glucose reabsorption and, thus, are used to treat patients with type 2 diabetes mellitus. Clinical trials coincidentally showed that SGLT2 inhibitors also benefitted patients with heart failure. This review explores the impact of SGLT2 inhibitors on other aspects of cardiovascular disease and skeletal health. In some, but not all, clinical and preclinical studies, SGLT2 inhibitors are found to reduce serum levels of free fatty acids and triglycerides. Their effects on total and low-density lipoprotein cholesterol and cardiac function also vary. However, SGLT2 inhibitors reduce lipid accumulation in the liver, kidney, and heart, and alter expression of lipid metabolism genes. Effects on free fatty acid uptake in abdominal fat depots depend on the location of adipose tissue. In male, but not female, mice, SGLT2 inhibitors reduce the atherosclerotic lesions and aortic calcium deposition. With respect to skeletal health, recent literature has reported conflicting associations with the risks of fracture and amputation. Studies suggest that SGLT2 inhibitors reduce tissue lipid accumulation, and in a sex-dependent manner, atherosclerosis and vascular calcification. However, their effects on lipid levels and bone health are complex and remain to be established.

Host cells reprogram lipid droplet synthesis through YY1 to resist PRRSV infection.

Metabolism in host cells can be modulated after viral infection, favoring viral survival or clearance. Here, we report that lipid droplet (LD) synthesis in host cells can be modulated by yin yang 1 (YY1) after porcine reproductive and respiratory syndrome virus (PRRSV) infection, resulting in active antiviral activity. As a ubiquitously distributed transcription factor, there was increased expression of YY1 upon PRRSV infection both in vitro and in vivo. YY1 silencing promoted the replication of PRRSV, whereas YY1 overexpression inhibited PRRSV replication. PRRSV infection led to a marked increase in LDs, while YY1 knockout inhibited LD synthesis, and YY1 overexpression enhanced LD accumulation, indicating that YY1 reprograms PRRSV infection-induced intracellular LD synthesis. We also showed that the viral components do not colocalize with LDs during PRRSV infection, and the effect of exogenously induced LD synthesis on PRRSV replication is nearly lethal. Moreover, we demonstrated that YY1 affects the synthesis of LDs by regulating the expression of lipid metabolism genes. YY1 negatively regulates the expression of fatty acid synthase (FASN) to weaken the fatty acid synthesis pathway and positively regulates the expression of peroxisome proliferator-activated receptor gamma (PPARγ) to promote the synthesis of LDs, thus inhibiting PRRSV replication. These novel findings indicate that YY1 plays a crucial role in regulating PRRSV replication by reprogramming LD synthesis. Therefore, our study provides a novel mechanism of host resistance to PRRSV and suggests potential new antiviral strategies against PRRSV infection.IMPORTANCEPorcine reproductive and respiratory virus (PRRSV) has caused incalculable economic damage to the global pig industry since it was first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. It is well known that viruses are parasitic pathogens, and the completion of their replication life cycle is highly dependent on host cells. A better understanding of host resistance to PRRSV infection is essential for developing safe and effective strategies to control PRRSV. Here, we report a crucial host antiviral molecule, yin yang 1 (YY1), which is induced to be expressed upon PRRSV infection and subsequently inhibits virus replication by reprogramming lipid droplet (LD) synthesis through transcriptional regulation. Our work provides a novel antiviral mechanism against PRRSV infection and suggests that targeting YY1 could be a new strategy for controlling PRRSV.

Lipid-encapsulated mRNA encoding an extended serum half-life interleukin-22 ameliorates metabolic disease in mice

ObjectiveInterleukin (IL)-22 is a potential therapeutic protein for the treatment of metabolic diseases such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease due to its involvement in multiple cellular pathways and observed hepatoprotective effects. The short serum half-life of IL-22 has previously limited its use in clinical applications; however, the development of mRNA-lipid nanoparticle (LNP) technology offers a novel therapeutic approach that uses a host-generated IL-22 fusion protein. In the present study, the effects of administration of an mRNA-LNP encoding IL-22 on metabolic disease parameters was investigated in various mouse models. MethodsC57BL/6NCrl mice were used to confirm mouse serum albumin (MSA)-IL-22 protein expression prior to assessments in C57BL/6NTac and CETP/ApoB transgenic mouse models of metabolic disease. Mice were fed either regular chow or a modified amylin liver nonalcoholic steatohepatitis–inducing diet prior to receiving either LNP-encapsulated MSA-IL-22 or MSA mRNA via intravenous or intramuscular injection. Metabolic markers were monitored for the duration of the experiments, and postmortem histology assessment and analysis of metabolic gene expression pathways were performed. ResultsMSA-IL-22 was detectable for ≥8 days following administration. Improvements in body weight, lipid metabolism, glucose metabolism, and lipogenic and fibrotic marker gene expression in the liver were observed in the MSA-IL-22–treated mice, and these effects were shown to be durable. ConclusionsThese results support the application of mRNA-encoded IL-22 as a promising treatment strategy for metabolic syndrome and associated comorbidities in human populations.

(+)Alpha-Lipoic Acid Regulates Lipid Metabolism Gene Expression and Lipidic Profile in a Cellular Model of Fatty Acid Overload

(+)Alpha-Lipoic Acid Regulates Lipid Metabolism Gene Expression and Lipidic Profile in a Cellular Model of Fatty Acid Overload

Amelioration of Insulin Resistance by Whey Protein in a High-Fat Diet-Induced Pediatric Obesity Male Mouse Model.

This study examined whey protein's impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. At 12 weeks old, their body weight, fasting blood glucose (FBG), blood insulin level (IRI), homeostatic model assessment for insulin resistance (HOMA-IR), liver lipid metabolism gene expression, and liver metabolites were compared. The whey group showed significantly lower body weight than the casein group at 12 weeks old (p = 0.034). FBG was lower in the whey group compared to the high-fat diet group (p < 0.01) and casein group (p = 0.058); IRI and HOMA-IR were reduced in the whey group compared to the casein group (p = 0.02, p < 0.01, p < 0.01, respectively). The levels of peroxisome proliferator-activated receptor α and hormone-sensitive lipase were upregulated in the whey group compared to the casein group (p < 0.01, p = 0.03). Metabolomic analysis revealed that the levels of taurine and glycine, both known for their anti-inflammatory and antioxidant properties, were upregulated in the whey group in the liver tissue (p < 0.01, p < 0.01). The intake of whey protein was found to improve insulin resistance in a high-fat diet-induced pediatric obesity mouse model.

#1326 Impairment of ACSS2 aggravates renal fibrosis and cell senescence during aging

Abstract Background and Aims Age-related changes in kidney function, structure, and their relationships have been extensively recognized recently. Here, we report that acyl-CoA synthetase short chain family member 2 (Acss2) as a regulator of lipid metabolism, play an important role in age-associated renal fibrosis. Method 21-month-old Acss2 knockout (Acss2−/−) mice were used as the renal aging models, and H2O2 also was used to induced renal tubular epithelial cells (TCMK-1) senescence. Serum creatinine (Cr) and urinary protein creatinine ratio (UACR) were measured to evaluate kidney function, and renal tissue lesions were observed by HE staining and Masson staining. The expression of gene/protein in relation to inflammation, fibrosis and cell senescence were measured by qPCR, western blot. SA-β-gal staining also used to assess cell senescence. Results The results indicate that Acss2 was decreased in aging mice, Acss2 knockout impaired renal function as detected by increased UACR. Additionally, HE and Masson staining showed that Acss2 deficiency was associated with more glomerular sclerosis and fibrosis (Fig. 1). RT-qPCR and Western blotting also revealed that Acss2 enhanced kidney fibrosis and cell senescence, accompanied by an increase in SA-β-gal-positive senescent cells (Fig. 2). These phenomena were most apparent in the TCMK cells treated with Acss2 siRNA and H2O2 (Fig. 3). What's more, KEGG analysis showed that fatty acid metabolism changes significantly during aging in kidney, and Acss2 knockout could impact the expression of lipid metabolism genes (Fig. 4) Conclusion Acss2 is associated with renal aging, and it may played a role in renal fibrosis and cell senescence by regulating fatty acid metabolism.

Insights into the molecular mechanisms of malnutrition-associated steatohepatitis: A review.

Malnutrition is a public health epidemic mainly targeting poverty-stricken people, young ones, older people, pregnant women, and individuals with metabolic disorders. Severe malnutrition is linked with several metabolic defects, such as hepatic dysfunction, hypertension, cardiovascular disease, and osteoarthritis. The proper functioning of the liver plays a crucial role in ensuring the supply of nutrients to the body. Consequently, inadequate nutrition can lead to severe periportal hepatic steatosis due to compromised mitochondrial and peroxisome functions. Reduced protein intake disrupts essential metabolic processes like the TCA cycle, oxidative phosphorylation, and β-oxidation, ultimately affecting ATP production. Furthermore, this can trigger a cascade of events, including disturbances in amino acid metabolism, iron metabolism, and gut microbiota, which activate genes involved in de novo lipogenesis, leading to the accumulation of lipids in the liver. The condition, in prolonged cases, progresses to steatohepatitis and liver fibrosis. Limited therapeutic solutions are available; however, few dietary supplements and drugs have demonstrated positive effects on the growth and health of malnourished individuals. These supplements improve parameters such as inflammatory and oxidative status, reduce triglyceride accumulation, enhance insulin sensitivity, and downregulate gene expression in hepatic lipid metabolism. This review elucidates the various mechanisms involved in malnutrition-associated steatohepatitis and provides an overview of the available approaches for treating this condition.

Bruceine A alleviates alcoholic liver disease by inhibiting AIM2 inflammasome activation via activating FXR

BackgroundAlcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic steatosis accompanied by inflammation is an initial and inevitable stage in the complex progression of simple alcoholic liver injury to more severe liver diseases such as hepatitis, liver fibrosis, cirrhosis and liver cancer. PurposeWe aimed to identify the therapeutic role of Bruceine A (BA) in ALD whilst attempting to explore whether its protective effects depend specifically on the farnesoid X receptor (FXR). MethodsAutodock was applied to detect the affinity between BA and FXR. Lieber-DeCarli liquid diet with 5 % ethanol (v/v) was adopted to establish the mouse ALD model. The lentivirus mediating FXR (LV-FXR) was injected into mice via the tail vein to establish FXR-overexpressed mice. FXR silencing or overexpression plasmids were transfected into AML-12 cells prior to ethanol stimulation. Quantitative real-time PCR, Western blotting and immunofluorescence assays were employed to determine the expression of related genes. We subjected liver sections to H&E and Oil Red O staining to evaluate the liver histological injury and the deposition of lipid droplets. ResultsBA significantly reduced body weight and liver-to-body weight ratios as well as biochemical indexes in mice. Ethanol-induced liver damage and lipid accumulation could be alleviated by BA treatment. BA bound to FXR by two hydrogen bonds. There was a positive correlation between BA administration and FXR expression. BA inhibited the expression of lipid synthesis genes and enhanced the expression of lipid metabolism genes by activating FXR, thus alleviating steatosis in ALD. Moreover, BA exerted an ameliorative effect against inflammation by inhibiting the activation of absent in melanoma 2 (AIM2) inflammasome by activating FXR. FXR overexpression possessed the ability to counter the accumulation of lipid and the activation of AIM2 inflammasome caused by ethanol. FXR deficiency exacerbated ethanol-induced liver steatosis and inflammation. The hepatoprotective effect of BA could be disrupted by FXR antagonist guggulsterone (GS) in vivo and FXR siRNA in vitro. ConclusionBA alleviated alcoholic liver disease by inhibiting AIM2 inflammasome activation through an FXR-dependent mechanism. This study may potentially represent a new therapeutic approach for ALD.

Effect of Algae Supplementation on the Gene Expression of Liver Lipid Metabolism in Dairy Goat Bucks

This study aimed to investigate how diets supplemented with DHA-rich algae affect the expression of liver lipid synthesis genes in dairy goat bucks. The results revealed that when supplemented with DHA-rich algae, liver weight and serum HDL-C were significantly increased (p &lt; 0.05), as well as serum LDL-C was significantly decreased (p &lt; 0.05). Transcriptome sequencing indicated that algae supplementation alters liver gene expression. The differentially expressed genes were predominantly enriched in fatty acid metabolism and the biosynthesis of unsaturated fatty acids. The expression of fatty acid desaturation and transcription factors (SCD, FADS1, INSIG1), de novo synthesis fatty acids (FASN), fatty acid transport (LDLR), and cholesterol and steroid synthesis (HMGCR, HMGCS1, SQLE) genes were significantly increased (p &lt; 0.05), and fatty acid oxidation (ALDH3B1) genes were significantly decreased (p &lt; 0.05). In conclusion, this research provided preliminary evidence that supplementation with algae in dietary supplements altered the expression of the liver lipid synthesis genes in the Saanen dairy goat bucks.

Lipid Deficiency Contributes to Impaired Alveolar Progenitor Cell Function in Aging and Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated interstitial lung disease resulting from repeated epithelial injury and inadequate epithelial repair. Alveolar type II cells (AEC2s) are progenitor cells that maintain epithelial homeostasis and repair the lung after injury. In the current study, we assessed lipid metabolism in AEC2s from human lungs of patients with IPF and healthy donors, as well as AEC2s from bleomycin-injured young and old mice. Through single-cell RNA sequencing, we observed that lipid metabolism-related genes were downregulated in IPF AEC2s and bleomycin-injured mouse AEC2s. Aging aggravated this decrease and hindered recovery of lipid metabolism gene expression in AEC2s after bleomycin injury. Pathway analyses revealed downregulation of genes related to lipid biosynthesis and fatty acid β-oxidation in AEC2s from IPF lungs and bleomycin-injured, old mouse lungs compared with the respective controls. We confirmed decreased cellular lipid content in AEC2s from IPF lungs and bleomycin-injured, old mouse lungs using immunofluorescence staining and flow cytometry. Futhermore, we show that lipid metabolism was associated with AEC2 progenitor function. Lipid supplementation and PPARγ (peroxisome proliferator activated receptor γ) activation promoted progenitor renewal capacity of both human and mouse AEC2s in three-dimensional organoid cultures. Lipid supplementation also increased AEC2 proliferation and expression of SFTPC in AEC2s. In summary, we identified a lipid metabolism deficiency in AEC2s from lungs of patients with IPF and bleomycin-injured old mice. Restoration of lipid metabolism homeostasis in AEC2s might promote AEC2 progenitor function and offer new opportunities for therapeutic approaches to IPF.

Effects of Dietary Gracilaria lichenoides and Bacillus amyloliquefaciens on Growth Performance, Antioxidant Capacity, and Intestinal Health of Penaeus monodon.

This research sought to assess the effects of dietary supplements with Gracilaria lichenoides and Bacillus amyloliquefaciens, either individually or combined, on the growth performance, antioxidant capacity, and intestinal function of Penaeus monodon. A total of 840 shrimps were randomly assigned to 28 tanks with an average initial weight of (1.04 ± 0.03) g (30 shrimp per tank) with 7 different treatment groups and 4 replicates per treatment. The control treatment (C) consisted of a basal diet; in contrast, the experimental groups were complement with varying levels of G. lichenoides (3% or 8%), either alone (S3 and S8) or in combination with B.amyloliquefaciens at different concentrations (3% G. lichenoides and 109 CFU/g-S3B9; 8% G. lichenoides and 1011 CFU/g B. amyloliquefaciens-S8B11; 109 CFU/g B. amyloliquefaciens-S9; 1011 CFU/g B. amyloliquefaciens-B11). The results indicated that the maximum values of final body weight (FBW) (10.49 ± 0.90) g, weight gain rate (WGR) (908.94 ± 33.58) g, and specific growth rate (SGR) (4.20 ± 0.06) g were perceived in the 3% G. lichenoide diet treatment, and compared with the control group, the difference was significant (p < 0.05). The whole-body lipid content of shrimp in the B9 group was significantly higher than that in the B11 group (p < 0.05), but no significant difference was observed when compared with shrimp fed other diets (p > 0.05). The ash content of shrimp in the B9 group was found to be significantly higher than that in the S3B9 group (p < 0.05). Furthermore, the lipase activity in the stomach and intestines of the experimental groups exhibited a statistically significantly increase compared to the control (p < 0.05). In comparison to the control group, the hepatopancreas of the S3 group exhibited a significant increase in the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and antioxidant genes [SOD, catalase (CAT), GSH-Px, thioredoxin (Trx), Hippo, and NF-E2-related factor 2 (Nrf2)] expression levels (p < 0.05). Additionally, the activities of total antioxidant capacity (T-AOC), SOD, peroxidase (POD), and antioxidant genes (CAT, GSH-Px, Trx, and Hippo) in the S3B9 treatment of hepatopancreas showed significant improvement (p < 0.05). The inclusion of dietary G. lichenoides and B. amyloliquefaciens resulted in enhanced relative expression of intestinal lipid metabolism genes (fatty acid synthetase (FAS), lipophorin receptor (LR), fatty acid transport protein 1 (FATP1)) and suppressed the expression of the long-chain fatty acid-CoA ligase 4 (LCL4) gene. Analysis of microbiota sequencing indicated improvements in composition and structure, with notable increases in Firmicutes at the phylum level and Vibrio at the genus level in the S3 group, as well as an increase in Tenericutes at the genus level in the S8B11 group. Overall, the inclusion of dietary G. lichenoides and B. amyloliquefaciens positively impacted the growth, antioxidant capacity, and microbial composition of shrimp, with particular enhancement observed in shrimp fed a supplementary 3% G. lichenoides diet.

Grb7 Ablation in Mice Improved Glycemic Control, Enhanced Insulin Signaling, and Increased Abdominal fat Mass in Females.

Growth factor receptor bound protein 7 (GRB7) is a multidomain signaling adaptor. Members of the Grb7/10/14 family, specifically Gbrb10/14, have important roles in metabolism. We ablated the Grb7 gene in mice to examine its metabolic function. Global ablation of Grb7 in FVB/NJ mice was generated. Growth, organ weight, food intake, and glucose homeostasis were measured. Insulin signaling was examined by Western blotting. Fat and lean body mass was measured by nuclear magnetic resonance, and body composition after fasting or high-fat diet was assessed. Energy expenditure was measured by indirect calorimetry. Expression of adiposity and lipid metabolism genes was measured by quantitative PCR. Grb7-null mice were viable, fertile, and without obvious phenotype. Grb7 ablation improved glycemic control and displayed sensitization to insulin signaling in the liver. Grb7-null females but not males had increased gonadal white adipose tissue mass. Following a 12-week high-fat diet, Grb7-null female mice gained fat body mass and developed relative insulin resistance. With fasting, there was less decrease in fat body mass in Grb7-null female mice. Female mice with Grb7 ablation had increased baseline food intake, less energy expenditure, and displayed a decrease in the expression of lipolysis and adipose browning genes in gonadal white adipose tissue by transcript and protein analysis. Our study suggests that Grb7 is a negative regulator of glycemic control. Our results reveal a role for Grb7 in female mice in the regulation of the visceral adipose tissue mass, a powerful predictor of metabolic dysfunction in obesity.