scholarly journals Animal biosynthesis of complex polyketides in a photosynthetic partnership

2019 ◽  
Author(s):  
Joshua P. Torres ◽  
Zhenjian Lin ◽  
Jaclyn M. Winter ◽  
Patrick J. Krug ◽  
Eric W. Schmidt
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
Acid Metabolism ◽  
Chemical Diversity ◽  
Host Cells ◽  
Symbiotic Bacteria ◽  
Plant Metabolism ◽  
Animal Host ◽  
Complex Products

ABSTRACTAnimals are rich sources of complex polyketides, including pharmaceuticals, cosmetics, and other products. Most polyketides are associated with microbial or plant metabolism1. For this reason, symbiotic bacteria or dietary organisms are often the true producers of compounds found in animals2,3. Although increasing evidence suggests that animals themselves make some compounds4–7, the origin of most polyketides in animals remains unknown. This problem makes it difficult to supply useful animal compounds as drugs and severely constrains our understanding of chemical diversity and the scope of biosynthesis in nature. Here, we demonstrate that animals produce microbe-like complex polyketides. We report a previously undocumented but widespread branch of fatty acid synthase- (FAS)-like proteins that have been retooled by evolution to synthesize complex products. One FAS-like protein uses only methylmalonyl-CoA as a substrate, otherwise unknown in animal lipid metabolism, and is involved in an intricate partnership between a sea slug and captured chloroplasts. The enzyme’s complex, methylated polyketide product results from a metabolic interplay between algal chloroplasts and animal host cells, and also likely facilitates the survival of both symbiotic partners, acting as a photoprotectant for plastids and an antioxidant for the slug8–12. Thus, we find that animals can unexpectedly synthesize a large and medically useful class of structurally complex polyketides previously ascribed solely to microbes, and can use them to promote symbiotic organelle maintenance. Because this represents an otherwise uncharacterized branch of polyketide and fatty acid metabolism, we anticipate a large diversity of animal polyketide products and enzymes awaiting discovery.

Placental Accumulation of Triacylglycerols in Gestational Diabetes Mellitus and Its Association with Altered Fetal Growth are Related to the Differential Expressions of Proteins of Lipid Metabolism

2020 ◽  
Author(s):  
Manoharan Balachandiran ◽  
Zachariah Bobby ◽  
Gowri Dorairajan ◽  
Sajini Elizabeth Jacob ◽  
Victorraj Gladwin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fetal Growth ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Acid Oxidation ◽  
Placental Proteins

Abstract Introduction Gestational diabetes mellitus (GDM) exhibit altered placental lipid metabolism. The molecular basis of this altered metabolism is not clear. Altered placental expression of proteins of lipogenesis and fatty acid oxidation may be involved in the placental accumulation of triacylglycerols (TG). The present study was aimed at investigating the differential expressions of placental proteins related to lipid metabolism among GDM women in comparison with control pregnant women (CPW) and to correlate them with maternal and fetal lipid parameters as well as altered fetal growth. Materials and Methods Maternal blood, cord blood, and placental samples were collected from GDM and CPW. The biochemical parameters, glucose, lipid profile and free fatty acids (FFA) were measured. The placental TG content was measured. Differential placental expressions of proteins; phosphatidylinositol-3-kinase (PI3K) p85α, PI3K p110α,liver X receptor alpha (LXRα), sterol regulatory element binding protein1(SREBP1), fatty acid synthase (FAS), stearyl CoA desaturase1 (SCD1), lipoprotein lipase (LPL),Peroxisome proliferator-activated receptor (PPAR)α and PPARγ were analysed by western blotting and immunohistochemistry. Results Placental protein expressions of PI3K p110α, LXRα, FAS, SCD1, and LPL were found to be significantly higher, whereas PPARα and PPARγ were lower in GDM women compared with CPW. The placental TG content and cord plasma FFA were increased in GDM women compared with CPW. The placental TG content positively correlated with Ponderal index of GDM new-borns. Conclusion Differential expressions of placental proteins related to lipid metabolism in GDM might have led to placental TG accumulation. This might have contributed to the fetal overgrowth in GDM.

FC 102PD INDUCED ARTERIOLAR AND PERITONEAL PATHOMECHANISMS ARE PARTIALLY REVERSED AFTER KIDNEY TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Conghui Zhang ◽  
Maria Bartosova ◽  
Betti Schaefer ◽  
Rebecca Herzog ◽  
Rimante Cerkauskiene ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Parietal Peritoneum ◽  
Gene Set Enrichment Analysis ◽  
Biological Processes ◽  
Cell Counts

Abstract Background and Aims Due to the unphysiological composition of PD fluids, chronic peritoneal dialysis (PD) induces progressive peritoneal fibrosis, hypervascularization, and vasculopathy. The evolution of the PD membrane and vasculopathy following kidney transplantation (KTx) is largely unknown. Method Arteriolar and peritoneal tissues were obtained from 107 children with chronic kidney disease (CKD5), 72 children on PD (treated with neutral pH PD fluids, with low glucose degradation product content, GDP) and 21 children, who underwent KTx 4-5 weeks after a median 21 months of PD. Specimen underwent standardized digital quantitative histomorphometry. Molecular mechanisms were studied in omental arterioles microdissected from surrounding fat by multi-omics followed by Gene Set Enrichment Analysis (GSEA); key findings were validated in parietal tissues of independent, matched cohorts by quantitative immunohistochemistry (n=15/group). Results Arteriolar transcriptome and proteome GSEA revealed suppression of leucocyte migration and T-cell activation / secretory pathways regulation, of sprouting angiogenesis biological processes and of epithelial proliferation and cell cycle after KTx as compared to PD. Lipid / fatty acid metabolism, autophagy and ATP synthesis pathways were activated. Transcriptome analysis including KTx, PD and CKD5 specifically attributed regulation of arteriolar lipid and fatty acid metabolism to transplantation and comprised 140 transcripts; their regulation was confirmed on the proteome level. Hub gene fatty acid synthase was identified by protein interaction analysis (string-db.org). 15 arteriolar genes activated by PD were inactivated after KTx and included glucose metabolisms and cytoskeleton related transcripts. 24 transcripts and 10 corresponding proteins induced by PD were still active after KTx and associated with biological processes related to TGF-ß signaling, fibrosis and mineral absorption. In line with arteriolar multi-omics findings, peritoneal hypervascularization induced by chronic PD was reversed after Tx to CKD5 level. CD45 positive tissue infiltrating leucocytes count was reduced by 40% and was independently associated with microvessel density in multivariable analysis including PD vintage, daily GDP exposure and recent KTx. Peritoneal lymphatic vessel density, submesothelial thickness, activated fibroblast, fibrin deposit, macrophage and EMT cell counts remained unchanged after KTx compared to PD. Arteriolar lumen to vessel ratios (a marker of vasculopathy) were similar in both groups. Vessel-homeostasis-related proteins in independent, matched cohorts demonstrated increased caspase-3 abundance in peritoneal arterioles after KTx. Arteriolar VEGF-A, thrombospondin, angiopoietin1/2, and hypoxia-inducible factor-1 (HIF-1a) were unchanged, while submesothelial HIF-1a and angiopoietin1/2 were decreased after Tx, favoring vessel maturation. The abundance of the key driver of fibrosis, TGF-ß-effector pSMAD2/3, was unchanged in the peritoneum and arterioles after Tx. Conclusion Our multi-omics analyses of fat covered omental arterioles, not directly exposed to PD fluids, demonstrate inhibition of PD induced immune response and angiogenesis pathways, of glucose metabolism and cytoskeleton regulation to levels similar as seen in children with CKD5. Arteriolar lipid and fatty acid metabolism is selectively altered after KTx. Reversal of low GDP PD induced hypervascularization and inflammation of the parietal peritoneum after KTx, mirror molecular changes in omental arterioles, while profibrotic activity persists after KTx in omental arterioles and in the parietal peritoneum.

scholarly journals Diospyros kaki and Citrus unshiu Mixture Improves Disorders of Lipid Metabolism in Nonalcoholic Fatty Liver Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Mi-Rae Shin ◽  
Sung Ho Shin ◽  
Seong-Soo Roh
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Diospyros Kaki ◽  
Citrus Unshiu ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) has been a major cause of a chronic liver disease over recent decades and increasing worldwide in parallel with the remarkable growth of obesity. In the present study, we investigate the ameliorative effects of PCM, a combination of Diospyros kaki fruit and Citrus unshiu peel mixture, on high-fat diet- (HFD-) induced NAFLD and clarify the potential mechanisms. PCM in HFD-fed mice was orally administered at a dose of 50 or 100 mg/kg subsequently for 2 months. Thereafter, lipid metabolism parameters and fat synthesis-related genes in the mouse liver were evaluated. Subsequently, body weight changes, liver weight, serum liver function and lipid profiles, and liver pathology were examined, and the relative levels of fatty acid synthesis and β-oxidation gene expression were evaluated by western blot. Serum AST, ALT, and TG levels in the HFD control mice were significantly higher than those of normal mice. Compared with HFD control mice, PCM supplementation increased phosphorylation of AMP-activated protein kinase (AMPK). Peroxisome proliferator-activated receptor (PPAR) α was significantly increased by PCM administration. Continuously, the activation of PPARα significantly elevated carnitine palmitoyltransferase 1 (CPT-1), a key enzyme in fatty acid β-oxidation, and mitochondrial uncoupling protein 2 (UCP-2), thermogenic regulatory genes, in PCM-treated mice compared with those of HFD control mice. Moreover, PCM inhibits lipogenesis and cholesterol synthesis via suppression of sterol regulatory element binding protein-1 (SREBP-1) and SREBP-2 and its target genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Taken together, these effects were mediated through activation of AMPK. In the conclusion, PCM improved liver damage in HFD-fed mice and attenuated NAFLD by the activation of PPARα and the inhibition of SREBPs expression via AMPK-dependent pathways.

scholarly journals Fatty acid synthase promotes breast cancer metastasis by mediating changes in fatty acid metabolism

2020 ◽  
Vol 21 (1) ◽  
pp. 1-1
Author(s):  
Shuo Xu ◽  
Tingting Chen ◽  
Lihua Dong ◽  
Tao Li ◽  
Hui Xue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthase ◽  
Cancer Metastasis ◽  
Acid Metabolism ◽  
Breast Cancer Metastasis

scholarly journals Molecular characteristic of activin receptor IIB and its functions in growth and nutrient regulation in Eriocheir sinensis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9673
Author(s):  
Jingan Wang ◽  
Kaijun Zhang ◽  
Xin Hou ◽  
Wucheng Yue ◽  
He Yang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
Eriocheir Sinensis ◽  
Negative Regulator ◽  
Control Group ◽  
Molting Cycle ◽  
Activin Receptor ◽  
Activin Receptor Iib

Activin receptor IIB (ActRIIB) is a serine/threonine-kinase receptor binding with transforming growth factor-β (TGF-β) superfamily ligands to participate in the regulation of muscle mass in vertebrates. However, its structure and function in crustaceans remain unknown. In this study, the ActRIIB gene in Eriocheir sinensis (Es-ActRIIB) was cloned and obtained with a 1,683 bp open reading frame, which contains the characteristic domains of TGF-β type II receptor superfamily, encoding 560 amino acids. The mRNA expression of Es-ActRIIB was the highest in hepatopancreas and the lowest in muscle at each molting stage. After injection of Es-ActRIIB double-stranded RNA during one molting cycle, the RNA interference (RNAi) group showed higher weight gain rate, higher specific growth rate, and lower hepatopancreas index compared with the control group. Meanwhile, the RNAi group displayed a significantly increased content of hydrolytic amino acid in both hepatopancreas and muscle. The RNAi group also displayed slightly higher contents of saturated fatty acid and monounsaturated fatty acid but significantly decreased levels of polyunsaturated fatty acid compared with the control group. After RNAi on Es-ActRIIB, the mRNA expressions of five ActRIIB signaling pathway genes showed that ActRI and forkhead box O (FoxO) were downregulated in hepatopancreas and muscle, but no significant expression differences were found in small mother against decapentaplegic (SMAD) 3, SMAD4 and mammalian target of rapamycin. The mRNA expression s of three lipid metabolism-related genes (carnitine palmitoyltransferase 1β (CPT1β), fatty acid synthase, and fatty acid elongation) were significantly downregulated in both hepatopancreas and muscle with the exception of CPT1β in muscles. These results indicate that ActRIIB is a functionally conservative negative regulator in growth mass, and protein and lipid metabolism could be affected by inhibiting ActRIIB signaling in crustacean.

scholarly journals The effect of fetal pig size and stage of gestation on tissue fatty acid metabolism and profile

Reproduction ◽  
2005 ◽  
Vol 129 (6) ◽  
pp. 757-763 ◽  
Author(s):  
Christopher J McNeil ◽  
Angela M Finch ◽  
Kenneth R Page ◽  
Steve D Clarke ◽  
Cheryl J Ashworth ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fetal Growth ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthase ◽  
Porcine Model ◽  
Acid Metabolism ◽  
Fatty Acid Status ◽  
Δ5 Desaturase ◽  
Acid Status ◽  
Δ6 Desaturase

The fetus requires an adequate supply of fatty acids for optimum growth and development. It has been hypothesized that reduced activity of enzymes of fatty acid metabolism could contribute to inadequate fetal growth. In a porcine model of differential fetal growth we examined heart and liver fatty acid synthase, Δ5-desaturase and Δ6-desaturase gene expression and measured hepatic fatty acid profile to assess long-chain polyunsaturated fatty acid status. On gestation days 45, 65 and 100 sows were killed and tissues extracted from an average-sized fetus and the smallest fetus from each litter. As early as day 45, considerable hepatic Δ5- and Δ6-desaturase was detected, and this expression significantly increased as gestation progressed. In contrast, cardiac desaturase expression remained stable with time. Fatty acid synthase expression was greatest at day 65 in the liver, but was not expressed in the heart. Overall, the smallest fetus did not exhibit reduced tissue Δ5- or Δ6-desaturase expression or compromised polyunsaturated fatty acid status at any stage. In fact, small fetuses expressed more cardiac Δ5-desaturase than their average-sized siblings, possibly in response to a stress to the heart. It is clear from this study that fatty acid metabolism changes markedly as gestation progresses, and reduced fatty acid supply does not cause inadequate growth in this porcine model of fetal development.

scholarly journals Identification of differentially expressed genes and pathways between intramuscular and abdominal fat-derived preadipocyte differentiation of chickens in vitro

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Meng Zhang ◽  
Fang Li ◽  
Xiang-fei Ma ◽  
Wen-ting Li ◽  
Rui-rui Jiang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Differentially Expressed Genes ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Adipogenic Differentiation ◽  
Abdominal Fat ◽  
Receptor Interaction ◽  
Preadipocyte Differentiation ◽  
Factors Affecting

Abstract Background The distribution and deposition of fat tissue in different parts of the body are the key factors affecting the carcass quality and meat flavour of chickens. Intramuscular fat (IMF) content is an important factor associated with meat quality, while abdominal fat (AbF) is regarded as one of the main factors affecting poultry slaughter efficiency. To investigate the differentially expressed genes (DEGs) and molecular regulatory mechanisms related to adipogenic differentiation between IMF- and AbF-derived preadipocytes, we analysed the mRNA expression profiles in preadipocytes (0d, Pre-) and adipocytes (10d, Ad-) from IMF and AbF of Gushi chickens. Results AbF-derived preadipocytes exhibited a higher adipogenic differentiation ability (96.4% + 0.6) than IMF-derived preadipocytes (86.0% + 0.4) (p < 0.01). By Ribo-Zero RNA sequencing, we obtained 4403 (2055 upregulated and 2348 downregulated) and 4693 (2797 upregulated and 1896 downregulated) DEGs between preadipocytes and adipocytes in the IMF and Ad groups, respectively. For IMF-derived preadipocyte differentiation, pathways related to the PPAR signalling pathway, ECM-receptor interaction and focal adhesion pathway were significantly enriched. For AbF-derived preadipocyte differentiation, the steroid biosynthesis pathways, calcium signaling pathway and ECM-receptor interaction pathway were significantly enriched. A large number of DEGs related to lipid metabolism, fatty acid metabolism and preadipocyte differentiation, such as PPARG, ACSBG2, FABP4, FASN, APOA1 and INSIG1, were identified in our study. Conclusion This study revealed large transcriptomic differences between IMF- and AbF-derived preadipocyte differentiation. A large number of DEGs and transcription factors that were closely related to fatty acid metabolism, lipid metabolism and preadipocyte differentiation were identified in the present study. Additionally, the microenvironment of IMF- and AbF-derived preadipocyte may play a significant role in adipogenic differentiation. This study provides valuable evidence to understand the molecular mechanisms underlying adipogenesis and fat deposition in chickens.

scholarly journals Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

2018 ◽  
Vol 49 (5) ◽  
pp. 1870-1884 ◽  
Author(s):  
Chian-Jiun Liou ◽  
Ciao-Han Wei ◽  
Ya-Ling Chen ◽  
Ching-Yi Cheng ◽  
Chia-Ling Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Epididymal Adipose Tissue ◽  
Obese Mice ◽  
High Fat

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

scholarly journals FABP5 coordinates lipid signaling that promotes prostate cancer metastasis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gregory Carbonetti ◽  
Tessa Wilpshaar ◽  
Jessie Kroonen ◽  
Keith Studholme ◽  
Cynthia Converso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Nuclear Receptor ◽  
Fatty Acid Synthase ◽  
Cancer Metastasis ◽  
Receptor Activation ◽  
Lipid Signaling ◽  
Fatty Acid Binding

AbstractProstate cancer (PCa) is defined by dysregulated lipid signaling and is characterized by upregulation of lipid metabolism-related genes including fatty acid binding protein 5 (FABP5), fatty acid synthase (FASN), and monoacylglycerol lipase (MAGL). FASN and MAGL are enzymes that generate cellular fatty acid pools while FABP5 is an intracellular chaperone that delivers fatty acids to nuclear receptors to enhance PCa metastasis. Since FABP5, FASN, and MAGL have been independently implicated in PCa progression, we hypothesized that FABP5 represents a central mechanism linking cytosolic lipid metabolism to pro-metastatic nuclear receptor signaling. Here, we show that the abilities of FASN and MAGL to promote nuclear receptor activation and PCa metastasis are critically dependent upon co-expression of FABP5 in vitro and in vivo. Our findings position FABP5 as a key driver of lipid-mediated metastasis and suggest that disruption of lipid signaling via FABP5 inhibition may constitute a new avenue to treat metastatic PCa.

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