Fatty Acid Synthase Research Articles

Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver

Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.) administration resulted in weight loss and absence of hepatic steatosis in wild-type (WT) and protein tyrosine phosphatase 1B (PTP1B)-deficient (KO) male mice. This protection relied on two central-peripheral axes connecting hypothalamic AMPK with brown/inguinal white adipose tissue (BAT/iWAT) uncoupling protein-1 (UCP-1) and hypothalamic JNK with hepatic fatty acid synthase (FAS). Herein, we addressed OLA i.p. treatment effects in WT and PTP1B-KO female mice. Contrarily to our previous results in WT females receiving OLA orally, the i.p. treatment did not induce weight gain or hyperphagia. Molecularly, in females OLA failed to diminish hypothalamic phospho-AMPK or elevate BAT UCP-1 and energy expenditure (EE) despite the preservation of iWAT browning. Conversely, OLA i.p. treatment in ovariectomized mice reduced hypothalamic phospho-AMPK, increased BAT/iWAT UCP-1 and EE, and induced weight loss as occurred in males. Pretreatment of hypothalamic neurons with 17β-estradiol (E2) abolished OLA effects on AMPK. Moreover, neither hypothalamic JNK activation nor hepatic FAS upregulation were found in WT and PTP1B-KO females receiving OLA via i.p. Importantly, this axis was reestablished upon ovariectomy. In this line, E2 prevented OLA-induced phospho-JNK in hypothalamic neurons. These results support the role of estrogens in sex-related dimorphism in OLA treatment. This study evidenced the benefit of OLA i.p. administration in preventing its obesogenic effects in female mice that could offer clinical value.

Investigation on the lipid-lowering effect and mechanism by combining turmeric with hawthorn in C57BL/6 obese mice.

Study on the hypolipidemic effect of turmeric combined with hawthorn on C57BL/6 obese mice and its possible mechanism. C57 mice were fed with 60% high-fat diet for 8 weeks to establish an obesity model, and 4 mice were slaughtered to verify whether the modeling was successful. The successful mice were divided into model group (HFD), positive group (high fat feed group [HFD]+simvastatin group [SIM]), turmeric group (HFD+TUR), hawthorn group (HFD+HAW), and para-medicine group (HFD+para-drug group [DOU]) for 4 weeks by gavage intervention. Different intervention groups had certain lipid-lowering effects, and the para-medicine group showed significant differences (p<0.05, p<0.01, p<0.001) in reducing serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, glutamic acid transaminase (ALT), glutamic acid transaminase (AST), and increasing high-density lipoprotein cholesterol. In the para-medicine group, the protein expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, platelet-reactive protein receptor 36, and CCAAT/enhancer binding protein α were significantly downregulated, and the protein expression of carnitine palmitoyl transferase1 and peroxisome proliferator-activated receptor α protein expression (p<0.01, p<0.001), thus suggesting that turmeric and hawthorn are superior to turmeric and hawthorn alone in enhancing lipid metabolism-related mechanisms. Combined effects of turmeric and hawthorn improve lipid metabolism in mice, protect the liver, and improve the protein expression of liver-related genes. This study can lay the theoretical basis for the future association of medicinal food products and the development of related weight loss products.

Effects of a diet supplemented with polysaccharides from Pogostemon cablin on growth performance, meat quality, and antioxidant capacity in Chongren Partridge chickens

In this study, the Pogostemon cablin polysaccharides (PCPs) were heteropolysaccharides with molecular weights of 63.17 kDa and 8.99 kDa, and their total carbohydrate content was 76.17 ± 0.23%, uronic acid content was 19.92 ± 0.42%, and protein content was 1.24 ± 0.07%. PCP is composed of arabinose, galactose, glucose, and glucuronic acid, with a molar ratio of 0.196:0.249:0.451:0.104. In addition, we further investigated the effects of the diet supplemented with different doses of PCP on growth performance, meat quality, and anti-oxidant capacity in Chongren Partridge chickens. A total of 200 chickens were randomly allocated into 4 treatments, and fed with a basal diet of 0 (CON), 200 (LPCP), 400 (MPCP), and 800 (HPCP) mg/kg PCP for a 14-day prefeeding period and a formal experimental period of 56 days. Results showed that dietary PCP significantly increased final body weight (BW), average daily gain (ADG), and decreased feed-to-gain ratio (F/G) from days 1 to 56. Meanwhile, dietary PCP reduced yellowness (b∗) values and increased redness (a∗) values at 24 h in breast muscles (p &amp;lt; 0.05). Furthermore, LPCP and MPCP significantly increased the level of guanylic acid (GMP) (p &amp;lt; 0.05). MPCP increased the content of free amino acids (isoleucine, leucine, lysine, methionine, threonine, valine, alanine, glutamic acid, serine, cysteine), total essential amino acid (EAA), total flavor amino acid (FAA), total AA, the content of fatty acids (c14:1, c16:1, and c22:2), and monounsaturated fatty acids (MUFAs) in the breast muscle when compared to CON (p &amp;lt; 0.05). In addition, MPCP significantly reduced the content of malondialdehyde (MDA) and increased the transcript abundances of fatty acid desaturase 2 (FADS2), fatty acid synthase (FAS), lipoprotein lipase (LPL), and sterol regulatory element binding protein-1 (SREBP-1) in the breast muscles of the chickens (p &amp;lt; 0.05). In light of the aforementioned results, PCP at 400 mg/kg could be used as an effective additive because it not only promotes the growth performance of Chongren Partridge chickens but also shows a conducive role in meat quality, especially in meat flavor.

Effect of high plant protein diet supplemented with Lysophospholipids-butyrate on the growth performance, liver health and intestinal morphology of Largemouth bass (Micropterus salmoides)

This study was conducted to evaluate the effects of dietary supplementation with lysophospholipids-butyrate (LPB) in a high plant protein diet on the growth performance, liver health, and intestinal morphology of Largemouth bass (Micropterus salmoides). Three experimental diets were formulated: a positive control diet (PC) containing 15.00 % soybean meal (SBM) and 13 % chicken meal；a high-plant-protein diet (HPP) with 28.00 % SBM; a diet (LPB) supplemented LPB at 0.1 % in HPP. Largemouth bass with an average initial body weight of 9.3 g were fed for 60 days, with 4 replicates per group and 20 fish per replicate. The results demonstrated that the HPP group exhibited significantly lower final body weight (FBW), weight gain rate (WGR) and specific growth rate (SGR) compared to the PC group. Moreover, the HPP diet induced a notable increase in liver collagen fiber and liver lipid content, which was alleviated by LPB supplementation. In comparison to the HPP group, the LPB group showed significant increases in serum albumin and albumin/globulin, along with a significant decrease in alanine aminotransferase activity (P < 0.05). Compared with the PC group, the mRNA levels of acetyl-CoA carboxylase-1 (ACC-1), diacylglycerol acyltransferase (DGAT), carnitine palmitoyl transferase-1 (CPT-1) and tumor necrosis factor-α (TNF-α) in HPP group were increased significantly (P < 0.05), while adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) as well as apoptotic gene B-cell lymphoma-2 (Bcl-2) were significantly down-regulated. The mRNA levels of fatty acid synthase (FAS), ACC-1, peroxisome proliferator activated receptor-α (PPAR-α), ATGL, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β) and Bcl-2 were up-regulated (P < 0.05), while DGAT and TNF-α were down-regulated in the LPB supplemented groups than that in the HPP group (P < 0.05). In conclusion, the supplementation of 0.1 % LPB can alleviate liver lipid accumulation and fibrosis caused by high level of soybean meal.

Nitrogen availability is important for preventing catastrophic mitosis in fission yeast.

Mitosis is a critical stage in the cell cycle, controlled by a vast network of regulators responding to multiple internal and external factors. The fission yeast Schizosaccharomyces pombe may demonstrate catastrophic mitotic phenotypes due to mutations or drug treatments. One of the factors provoking catastrophic mitosis is a disturbed lipid metabolism, resulting from e.g. mutations in acetyl-CoA/biotin carboxylase (cut6), in fatty acid synthase (fas2/lsd1), or in the transcriptional regulator of lipid metabolism (cbf11) genes, as well as treatment with inhibitors of fatty acid synthesis. It was previously shown that mitotic fidelity in lipid metabolism mutants can be partially rescued by ammonium chloride. In this study we demonstrate that mitotic fidelity can be improved by multiple nitrogen sources. Moreover, this improvement is not limited to lipid metabolism disturbances but also applies to a number of unrelated mitotic mutants. Interestingly, the partial rescue is not achieved by restoring the lipid metabolism state, but rather indirectly. Our results highlight a novel role for nitrogen availability in mitotic fidelity.

CRISPR-Cas9 mediated genome editing of Kluyveromyces marxianus for iterative, multiplexed gene disruption and pathway integration.

Kluyveromyces marxianus, a thermotolerant, fast-growing, Crabtree-negative yeast, is a promising chassis for the manufacture of various bioproducts. Although several genome editing tools are available for this yeast, these tools still require refinement to enable more convenient and efficient genetic modification. In this study, we engineered the K. marxianus NBRC 104275 strain by impairing the nonhomologous end joining and enhancing the homologous recombination machinery, which resulted in improved homology-directed repair effective on homology arms of up to 40 bp in length. Additionally, we simplified the CRISPR-Cas9 editing system by constructing a strain for integrative expression of Cas9 nuclease and plasmids bearing different selection markers for gRNA expression, thereby facilitating iterative genome editing without the need for plasmid curing. We demonstrated that tRNA was more effective than the hammerhead ribozyme for processing gRNA primary transcripts, and readily assembled tRNA-gRNA arrays were used for multiplexed editing of at least four targets. This editing tool was further employed for simultaneous scarless in vivo assembly of a 12-kb cassette from three fragments and marker-free integration for expressing a fusion variant of fatty acid synthase, as well as the integration of genes for starch hydrolysis. Together, the genome editing tool developed in this study makes K. marxianus more amenable to genetic modification and will facilitate more extensive engineering of this nonconventional yeast for chemical production.

Identification of FASN Gene Polymorphisms, Expression and Their Relationship with Body Size Traits in Guizhou White Goat (Capra hircus) with Different Genders

Identification of FASN Gene Polymorphisms, Expression and Their Relationship with Body Size Traits in Guizhou White Goat (Capra hircus) with Different Genders

Analysis of common differential gene expression in synovial cells of osteoarthritis and rheumatoid arthritis.

To elucidate potential molecular mechanisms differentiating osteoarthritis (OA) and rheumatoid arthritis (RA) through a bioinformatics analysis of differentially expressed genes (DEGs) in patient synovial cells, aiming to provide new insights for clinical treatment strategies. Gene expression datasets GSE1919, GSE82107, and GSE77298 were downloaded from the Gene Expression Omnibus (GEO) database to serve as the training groups, with GSE55235 being used as the validation dataset. The OA and RA data from the GSE1919 dataset were merged with the standardized data from GSE82107 and GSE77298, followed by batch effect removal to obtain the merged datasets of differential expressed genes (DEGs) for OA and RA. Intersection analysis was conducted on the DEGs between the two conditions to identify commonly upregulated and downregulated DEGs. Enrichment analysis was then performed on these common co-expressed DEGs, and a protein-protein interaction (PPI) network was constructed to identify hub genes. These hub genes were further analyzed using the GENEMANIA online platform and subjected to enrichment analysis. Subsequent validation analysis was conducted using the GSE55235 dataset. The analysis of differentially expressed genes in the synovial cells from patients with Osteoarthritis (OA) and Rheumatoid Arthritis (RA), compared to a control group (individuals without OA or RA), revealed significant changes in gene expression patterns. Specifically, the genes APOD, FASN, and SCD were observed to have lower expression levels in the synovial cells of both OA and RA patients, indicating downregulation within the pathological context of these diseases. In contrast, the SDC1 gene was found to be upregulated, displaying higher expression levels in the synovial cells of OA and RA patients compared to normal controls.Additionally, a noteworthy observation was the downregulation of the transcription factor PPARG in the synovial cells of patients with OA and RA. The decrease in expression levels of PPARG further validates the alteration in lipid metabolism and inflammatory processes associated with the pathogenesis of OA and RA. These findings underscore the significance of these genes and the transcription factor not only as biomarkers for differential diagnosis between OA and RA but also as potential targets for therapeutic interventions aimed at modulating their expression to counteract disease progression. The outcomes of this investigation reveal the existence of potentially shared molecular mechanisms within Osteoarthritis (OA) and Rheumatoid Arthritis (RA). The identification of APOD, FASN, SDC1, TNFSF11 as key target genes, along with their downstream transcription factor PPARG, highlights common potential factors implicated in both diseases. A deeper examination and exploration of these findings could pave the way for new candidate targets and directions in therapeutic research aimed at treating both OA and RA. This study underscores the significance of leveraging bioinformatics approaches to unravel complex disease mechanisms, offering a promising avenue for the development of more effective and targeted treatments.

Hepatic Expression of Genes Related to Fatty Acid Biosynthesis during Tropical Summer in Broilers: Effect of Organic Selenium Supplementation

Background: The physiological responses during adaptation to summer in poultry could be related to modulation of energy metabolism. Enhanced deposition of fat in spite of reduced feed intake seems to have an advantage under hot conditions. Thus, the present study was conducted to investigate the seasonal status of de novo synthesis of fatty acids in broiler chicken (Gallus gallus) and its response to organic selenium supplementation. Methods: The study was conducted in two phases, one during autumn and the other during summer, with a total of 300 birds as autumn control, summer control, group-I (0.3 ppm SeMet), group-II (0.6 ppm SeMet) and group-III (0.9 ppm SeMet) groups. Blood samples and hepatic tissues were collected at 21 and 42 d for further analysis. Result: An elevation in serum lipid profile, glucose, cortisol and T4 levels was observed during the summer while the T3 concentration decreased compared to the autumn. The hepatic expression of Acetyl Co. A carboxylase α (ACCα) and Fatty acid synthase (FASN) was increased at 21 d, while it was decreased at 42 d during summer in broilers. Serum total cholesterol levels and LDL levels decreased with SeMet at 0.6 and 0.9 ppm levels. The expression of hepatic ACCá and FASN genes was decreased with selenium supplementation at higher levels. Increased serum total cholesterol levels were associated with lower de novo fatty acid synthesis at 42d during summer in broilers.

Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered metabolism, cell senescence, and nonalcoholic fatty liver disease.

Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation by sirtuin 3. We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine-635 was mutated to glutamine (K635Q). Male Acss1K635Q/K635Q mice were smaller with higher metabolic rate and blood acetate and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1K635Q/K635Q mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis, consistent with nonalcoholic fatty liver disease (NAFLD). RNA sequencing analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD. Fasted Acss1K635Q/K635Q mouse livers showed increased fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1), both associated with NAFLD, and increased carbohydrate response element-binding protein binding to Fasn and Scd1 enhancer regions. Last, liver lipidomics showed elevated ceramide, lysophosphatidylethanolamine, and lysophosphatidylcholine, all associated with NAFLD. Thus, we propose that ACSS1-K635-Ac dysregulation leads to aberrant lipid metabolism, cellular senescence, and NAFLD.

Transcriptomic Insights into Host Metabolism and Immunity Changes after Parasitization by Leptopilina myrica.

Parasitoids commonly manipulate their host's metabolism and immunity to facilitate their offspring survival, but the mechanisms remain poorly understood. Here, we deconstructed the manipulation strategy of a newly discovered parasitoid wasp, L. myrica, which parasitizes D. melanogaster. Using RNA-seq, we analyzed transcriptomes of L. myrica-parasitized and non-parasitized Drosophila host larvae. A total of 22.29 Gb and 23.85 Gb of clean reads were obtained from the two samples, respectively, and differential expression analysis identified 445 DEGs. Of them, 304 genes were upregulated and 141 genes were downregulated in parasitized hosts compared with non-parasitized larvae. Based on the functional annotations in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, we found that the genes involved in host nutrition metabolism were significantly upregulated, particularly in carbohydrate, amino acid, and lipid metabolism. We also identified 30 other metabolism-related DEGs, including hexokinase, fatty acid synthase, and UDP-glycosyltransferase (Ugt) genes. We observed that five Bomanin genes (Boms) and six antimicrobial peptides (AMPs) were upregulated. Moreover, a qRT-PCR analysis of 12 randomly selected DEGs confirmed the reproducibility and accuracy of the RNA-seq data. Our results provide a comprehensive transcriptomic analysis of how L. myrica manipulates its host, laying a solid foundation for studies on the regulatory mechanisms employed by parasitoid wasps in their hosts.

High-confidence 3D template matching for cryo-electron tomography

Visual proteomics attempts to build atlases of the molecular content of cells but the automated annotation of cryo electron tomograms remains challenging. Template matching (TM) and methods based on machine learning detect structural signatures of macromolecules. However, their applicability remains limited in terms of both the abundance and size of the molecular targets. Here we show that the performance of TM is greatly improved by using template-specific search parameter optimization and by including higher-resolution information. We establish a TM pipeline with systematically tuned parameters for the automated, objective and comprehensive identification of structures with confidence 10 to 100-fold above the noise level. We demonstrate high-fidelity and high-confidence localizations of nuclear pore complexes, vaults, ribosomes, proteasomes, fatty acid synthases, lipid membranes and microtubules, and individual subunits inside crowded eukaryotic cells. We provide software tools for the generic implementation of our method that is broadly applicable towards realizing visual proteomics.

The impact of sericin on inflammation, oxidative stress, and lipid metabolism in female rats with experimental knee osteoarthritis.

This study investigated the effects of sericin on inflammation, oxidative stress, and lipid metabolism in female rats with experimental knee osteoarthritis (KOA), focusing on evaluating its effectiveness via the sterol regulatory protein (SREBP)-1C and SREBP-2 pathways. The rats were randomly assigned to three experimental groups: the C group (control), the KOA group (KOA control), and the sericin group (KOA + sericin). The KOA model was created by injecting monosodium iodoacetate (MIA) into the knee joint. Sericin was administered intra-articularly to rats on days 1, 7, 14, and 21 (0.8g/kg/mL, 50 µL). After 21days, the rats were sacrificed, and serum samples were analyzed using an ELISA to measure tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-10, SREBP-1c, SREBP-2, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), cholesterol, triglyceride, and total oxidant-antioxidant status (TOS-TAS) levels. The KOA group exhibited higher serum TNF-α, IL-1β, TOS, SREBP-1C, ACC, FAS, triglyceride, SREBP-2, and cholesterol levels than the C group (P < 0.05). However, the levels of these cytokines, except cholesterol, were significantly lower in the sericin group than in the KOA group. The KOA group exhibited significantly lower serum TAS and IL-10 levels than the C group (P < 0.05). In the sericin group, there was a statistically significant increase (P < 0.05). Sericin shows promising potential for reducing inflammation, oxidative stress, and lipid metabolism in experimental models of KOA in rats. However, further clinical research is necessary to validate the potential of sericin as a therapeutic agent for treating KOA. Key Points • Sericin can reduce knee osteoarthritis (KOA) symptoms in an experimental rat model. • In particular, in the serum of an experimental KOA rat model, sericin specifically reduces the levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), and increases the levels of anti-inflammatory cytokines, such as IL-10. • Sericin reduced lipid metabolism via the sterol regulatory protein (SREBP)-1C and SREBP-2 pathways and oxidative stress in the serum of the experimental KOA rat model. • The intra-articular administration of sericin has been shown to significantly reduce lipid metabolism, oxidative stress, and inflammation, as supported by biochemical analysis. These findings suggest its promising potential as an alternative treatment option for KOA.

PCB169 exposure aggravated the development of non-alcoholic fatty liver in high-fat diet-induced male C57BL/6 mice.

Polychlorinated biphenyls (PCBs) are lipophilic environmental toxicants. Epidemiological studies have established a link between PCBs and both metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Multiple studies have reported that exposure to both PCB156 and PCB126 among the 12 dioxin-like PCBs leads to the development of NAFLD. However, studies to elucidate whether PCB169 induces the development of NAFLD by constructing in vivo models have not been reported. Therefore, we evaluated the effects of exposure to PCB169 (5 mg/kg-bw) on hepatic lipid metabolism in C57BL/6 mice from control diet and high-fat diet cohorts. The results showed that PCB169 exposure reduced body weight and intraperitoneal fat mass in mice on the control diet, but the liver lipid levels were significantly increased, exacerbating NAFLD in mice on a high-fat diet. Through transcriptomics studies, it was found that PCB169 exposure induced significant up-regulation of Pparγ, Fasn, and Aacs genes involved in hepatic lipogenesis, as well as remarkable up-regulation of Hmgcr, Lss, and Sqle genes involved in cholesterol synthesis. Additionally, there was notable down-regulation of Pparα and Cpt1 genes involved in lipid β-oxidation, leading to abnormal lipid accumulation in the liver. In addition, we found that PCB169 exposure significantly activated the Arachidonic acid metabolism, PPAR signaling pathway, Metabolism of xenobiotics by cytochrome P450, and Retinol metabolism pathways, and so on. Our study suggests that PCB169 can modify gene expression related to lipid metabolism, augument lipid accumulation in the liver, and further contribute to the development of NAFLD, thereby revealing the detrimental effects associated with PCB exposure on animal growth and metabolism.

Effects of Mactra chinenesis Peptides on Alcohol-Induced Acute Liver Injury and Intestinal Flora in Mice.

Food-borne bioactive peptides have shown promise in preventing and mitigating alcohol-induced liver injury. This study was the first to assess the novel properties of Mactra chinenesis peptides (MCPs) in mitigating acute alcoholic liver injury in mice, and further elucidated the underlying mechanisms associated with this effect. The results showed that MCPs can improve lipid metabolism by modulating the AMPK signaling pathway, decreasing fatty acid synthase activity, and increasing carnitine palmitoyltransferase 1a activity. Meanwhile, MCPs ameliorate inflammation by inhibiting the NF-κB activation, leading to reduced levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β). Additionally, a 16S rDNA sequencing analysis revealed that MCPs can restore the balance of gut microbiota and increase the relative abundance of beneficial bacteria. These findings suggest that supplementation of MCPs could attenuate alcohol intake-induced acute liver injury, and, thus, may be utilized as a functional dietary supplement for the successful treatment and prevention of acute liver injury.

Chlorogenic acid and its isomers attenuate NAFLD by mitigating lipid accumulation in oleic acid-induced HepG2 cells and high-fat diet- fed zebrafish.

Chlorogenic acid (Chl), isochlorogenic acid A (Isochl A), and isochlorogenic acid B (Isochl B) are naturally occurring phenolic compounds, which have been shown to exert a regulatory effect on lipid metabolism. However, the mechanism underlying this effect remains unclear. Herein, we investigated the inhibitory effects and underlying mechanisms of these three phenolic compounds on oleic acid (OA)-induced HepG2 cells and high-fat diet (HFD)-fed zebrafish. Lipid accumulation and triacylglycerol levels increased in OA-induced cells, which was attenuated by Chl, Isochl A, and Isochl B. Moreover, the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) decreased, while superoxide dismutase (SOD) levels increased by Chl, Isochl A and Isochl B treatment. Western blot analysis demonstrated that Chl, Isochl A and Isochl B reduced the expression of lipogenesis-related protein, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, peroxisome proliferator-activated receptor alpha gamma (PPARα) was increased by Chl, Isochl A, and Isochl B treatment. In addition, our results indicated that Chl, Isochl A and Isochl B decreased lipid profiles and lipid accumulation in HFD-fed zebrafish.

Anti-adipogenic effect of heat-treated probiotic Lactiplantibacillus plantarum WB2719 and Lacticaseibacillus rhamnosus WB2804

Lactiplantibacillus plantarum WB2719 and Lacticaseibacillus rhamnosus WB2804 were isolated from fermented foods. These strains were demonstrated probiotic traits and anti-adipogenic effects. These strains exhibited tolerance to artificial gastric conditions and adhesion activities to intestine cells. Furthermore, heat-treated L. plantarum WB2719 and L. rhamnosus WB2804 inhibited preadipocyte differentiation by modulating peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding proteins α (C/EBP-α), and fatty acid synthase (FAS) expression. In particular, heat-treated L. plantarum WB2719 decreased mitosis and exerted anti-obesity effects by inducing apoptosis. Therefore, this study proposes the potential commercialization of heat-treated L. plantarum WB2719 and L. rhamnosus WB2804 as novel food-derived anti-obesity materials in the expanding health-functional food sector.

Metabolomics and microbiome co-analysis reveals altered innate immune responses in Charybdis japonica following Aeromonas hydrophila infection

A comprehensive bioinformatics analysis was conducted to elucidate the innate immune response of Charybdis japonica following exposure to Aeromonas hydrophila. This study integrated metabolomics, 16S rRNA sequencing, and enzymatic activity data to dissect the immune mechanisms activated in response to infection. Infection with A. hydrophila resulted in an increased abundance of beneficial intestinal genera such as Photobacterium spp., Rhodobacter spp., Polaribacter spp., Psychrilyobacter spp., and Mesoflavibacter spp. These probiotics appear to suppress A. hydrophila colonization by competitively dominating the intestinal microbiota. Key metabolic pathways affected included fatty acid biosynthesis, galactose metabolism, and nitrogen metabolism, highlighting their role in the crab's intestinal response. Enzymatic analysis revealed a decrease in activities of hexokinase, phosphofructokinase, and pyruvate kinase, which are essential for energy homeostasis and ATP production necessary for stress responses. Additionally, reductions were observed in the activities of acetyl-CoA carboxylase and fatty acid synthase. Gene expression analysis showed downregulation in Peroxiredoxin 1 (PRDX1), Peroxiredoxin 2 (PRDX2), glutathione-S-transferase (GST), catalase (CAT), and glutathione (GSH), with concurrent increases in malondialdehyde (MDA) levels, indicating severe oxidative stress. This study provides insights into the molecular strategies employed by marine crabs to counteract bacterial invasions in their natural habitat.

237 Disrupted insulin signaling due to an acute immune response in swine

Abstract Insulin is an anabolic hormone involved in glucose uptake and synthesis of fats, proteins, and glycogen. Altered insulin signaling can occur due to metabolic state, pathogen exposure, and autoimmune disorders. Lipopolysaccharide (LPS), an endotoxin secreted produced by gram-negative bacteria, can induce a severe, systemic immune response. In pigs, chronic LPS exposure has induced insulin resistance. However, the effects of acute exposure to LPS on insulin signaling and resistance have not been elucidated. Crossbred nursery pigs [n = 58, initial body weight (BW) = 12.1 kg ± 0.23 kg] were randomly assigned into two experimental subsets, where 10 animals were designated for repeated blood sampling and 48 animals underwent timed euthanasia for tissue collection. For repeated blood sampling, jugular catheters were placed under anesthesia and the animals were given 48 h to recover before being randomly assigned to treatments. These treatments were an intraperitoneal injection of either 15µg/kg BW LPS or an equal volume of 0.9% Saline (n = 5 pigs/treatment). Blood was collected for 48 h followed by euthanasia. The other 48 pigs were randomly assigned to the same treatments, and then randomly assigned to euthanasia timepoints of 0, 3, 6, 12, 24 or 48 h post injection for tissue collection. Among the catheterized pigs, 2-h post LPS challenge there was a decrease in serum insulin concentration (P &amp;lt; 0.05) and mild hyperglycemia (P &amp;lt; 0.05) post challenge. At 12- and 24-h post LPS challenge there was a decrease in insulin (P &amp;lt; 0.05) and a trend hyperglycemia was also apparent at 24 h (P = 0.063). In liver tissue, insulin related genes exhibited alterations post LPS injection. Phosphoinositide 3-kinase (pi3k) and insulin receptor substrate 1 (irs1) expression were decreased at 3 and 6 h (p&amp;lt; 0.05) and protein kinase b (akt) expression were decreased at 3 h (P &amp;lt; 0.05) post challenge. The expression of insulin inhibitor growth factor receptor bound protein 10 (grb10) was decreased at 6-, 12-, and 24-h after challenge (P &amp;lt; 0.05). Fructose-1-6-bisphosphatase (f16bp) expression was reduced at 3-, 6-, and 12-h (P &amp;lt; 0.05) in the liver while phosphoenolpyruvate carboxykinase (pepck) expression was decreased at 3- and 6-h (P &amp;lt; 0.01) post challenge. Other metabolic genes were decreased at 3-, 6-, and 12-h post LPS challenge, including fatty acid synthase (fas; P &amp;lt; 0.05), carbohydrate response element binding protein (chrebp; P &amp;lt; 0.05), and acetyl CoA carboxylase (acc; P &amp;lt; 0.05). Protein abundance of Akt 3 h after LPS injection was decreased in the liver (P &amp;lt; 0.05). In skeletal muscle 6 h post LPS injection, insulin receptor (insr), insulin-like growth factor receptor (igfr) and fas were all increased (P &amp;lt; 0.05) These results indicate disrupted insulin signaling at various levels after an acute immune response.

Taurine-mediated gene transcription and cell membrane permeability reinforced co-production of bioethanol and Monascus azaphilone pigments for a newly isolated Monascus purpureus

BackgroundTaurine, a semi-essential micronutrient, could be utilized as a sulfur source for some bacteria; however, little is known about its effect on the accumulation of fermentation products. Here, it investigated the effect of taurine on co-production of bioethanol and Monascus azaphilone pigments (MonAzPs) for a fungus.ResultsA newly isolated fungus of 98.92% identity with Monascus purpureus co-produced 23.43 g/L bioethanol and 66.12, 78.01 and 62.37 U/mL red, yellow and orange MonAzPs for 3 d in synthetic medium (SM). Taurine enhanced bioethanol titer, ethanol productivity and ethanol yield at the maximum by 1.56, 1.58 and 1.60 times than those of the control in corn stover hydrolysates (CSH), and red, yellow and orange MonAzPs were raised by 1.24, 1.26 and 1.29 times, respectively. Taurine was consumed extremely small quantities for M. purpureus and its promotional effect was not universal for the other two biorefinery fermenting strains. Taurine intensified the gene transcription of glycolysis (glucokinase, phosphoglycerate mutase, enolase and alcohol dehydrogenase) and MonAzPs biosynthesis (serine hydrolases, C-11-ketoreductase, FAD-dependent monooxygenase, 4-O-acyltransferase, deacetylase, NAD(P)H-dependent oxidoredutase, FAD-dependent oxidoredutase, enoyl reductase and fatty acid synthase) through de novo RNA-Seq assays. Furthermore, taurine improved cell membrane permeability through changing cell membrane structure by microscopic imaging assays.ConclusionsTaurine reinforced co-production of bioethanol and MonAzPs by increasing gene transcription level and cell membrane permeability for M. purpureus. This work would offer an innovative, efficient and taurine-based co-production system for mass accumulation of the value-added biofuels and biochemicals from lignocellulosic biomass.