scholarly journals Modulation of Fatty Acid Composition of Aspergillus oryzae in Response to Ethanol Stress

2019 ◽  
Vol 7 (6) ◽  
pp. 158 ◽  
Author(s):  
Long Ma ◽  
Lijun Fu ◽  
Zhihong Hu ◽  
Yongkai Li ◽  
Xing Zheng ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Aspergillus Oryzae ◽  
Target Genes ◽  
Significant Inhibition ◽  
Rice Starch ◽  
Ethanol Stress ◽  
Rice Wine ◽  
Mycelium Growth ◽  
Transmission Electron Microscopy Analysis ◽  
Koji Mold

The koji mold Aspergillus oryzae is widely adopted for producing rice wine, wherein koji mold saccharifies rice starch and sake yeast ferments glucose to ethanol. During rice wine brewing, the accumulating ethanol becomes a major source of stress for A. oryzae, and there is a decline in hydrolysis efficiency. However, the protective mechanisms of A. oryzae against ethanol stress are poorly understood. In the present study, we demonstrate that ethanol adversity caused a significant inhibition of mycelium growth and conidia formation in A. oryzae, and this suppressive effect increased with ethanol concentration. Transmission electron microscopy analysis revealed that ethanol uptake triggered internal cellular perturbations, such as irregular nuclei and the aggregation of scattered vacuoles in A. oryzae cells. Metabolic analysis uncovered an increase in fatty acid unsaturation under high ethanol conditions, in which a large proportion of stearic acid was converted into linoleic acid, and the expression of related fatty acid desaturases was activated. Our results therefore improve the understanding of ethanol adaptation mechanisms in A. oryzae and offer target genes for ethanol tolerance enhancement via genetic engineering.

scholarly journals Membrane Fluidity of Saccharomyces cerevisiae from Huangjiu (Chinese Rice Wine) Is Variably Regulated by OLE1 To Offset the Disruptive Effect of Ethanol

2019 ◽  
Vol 85 (23) ◽  
Author(s):  
Yijin Yang ◽  
Yongjun Xia ◽  
Wuyao Hu ◽  
Leren Tao ◽  
Li Ni ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Fatty Acid ◽  
Membrane Fluidity ◽  
Ethanol Tolerance ◽  
Acid Metabolism ◽  
Ethanol Stress ◽  
Disruptive Effect ◽  
Rice Wine ◽  
Chinese Rice Wine ◽  
High Ethanol

ABSTRACT An evolution and resequencing strategy was used to research the genetic basis of Saccharomyces cerevisiae BR20 (with 18 vol% ethanol tolerance) and the evolved strain F23 (with 25 vol% ethanol tolerance). Whole-genome sequencing and RNA sequencing (RNA-seq) indicated that the enhanced ethanol tolerance under 10 vol% ethanol could be attributed to amino acid metabolism, whereas 18 vol% ethanol tolerance was due to fatty acid metabolism. Ultrastructural analysis indicated that F23 exhibited better membrane integrity than did BR20 under ethanol stress. At low concentrations (<5 vol%), the partition of ethanol into the membrane increased the membrane fluidity, which had little effect on cell growth. However, the toxic effects of medium and high ethanol concentrations (5 to 20 vol%) tended to decrease the membrane fluidity. Under high ethanol stress (>10 vol%), the highly tolerant strain was able to maintain a relatively constant fluidity by increasing the content of unsaturated fatty acid (UFA), whereas less-tolerant strains show a continuous decrease in fluidity and UFA content. OLE1, which was identified as the only gene with a differential single-nucleotide polymorphism (SNP) mutation site related to fatty acid metabolism, was significantly changed in response to ethanol. The role of OLE1 in membrane fluidity was positively validated in its overexpressed transformants. Therefore, OLE1 lowered the rate of decline in membrane fluidity and thus enabled the yeast to better fight the deleterious effects of ethanol. IMPORTANCE Yeasts with superior ethanol tolerance are desirable for winemakers and wine industries. In our previous work, strain F23 was evolved with superior ethanol tolerance and fermentation activity to improve the flavor profiles of Chinese rice wine. Therefore, exploring the genomic variations and ethanol tolerance mechanism of strain F23 could contribute to an understanding of its effect on the flavor characteristics in the resulting Chinese rice wine. The cellular membrane plays a vital role in the ethanol tolerance of yeasts; however, how the membrane is regulated to fight the toxic effect of ethanol remains to be elucidated. This study suggests that the membrane fluidity is variably regulated by OLE1 to offset the disruptive effect of ethanol. Current work will help develop more ethanol-tolerant yeast strains for wine industries and contribute to a deep understanding of its high flavor-producing ability.

scholarly journals Aqueous Extract of Pepino Leaves Ameliorates Palmitic Acid-Induced Hepatocellular Lipotoxicity via Inhibition of Endoplasmic Reticulum Stress and Apoptosis

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 903
Author(s):  
Jen-Ying Hsu ◽  
Hui-Hsuan Lin ◽  
Charng-Cherng Chyau ◽  
Zhi-Hong Wang ◽  
Jing-Hsien Chen
Keyword(s):  
Fatty Acid ◽  
Palmitic Acid ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Target Genes ◽  
Liver Lipid ◽  
Antioxidant Response ◽  
Long Chain Fatty Acid ◽  
Nrf2 Expression

Saturated fatty acid is one of the important nutrients, but contributes to lipotoxicity in the liver, causing hepatic steatosis. Aqueous pepino leaf extract (AEPL) in the previous study revealed alleviated liver lipid accumulation in metabolic syndrome mice. The study aimed to investigate the mechanism of AEPL on saturated long-chain fatty acid-induced lipotoxicity in HepG2 cells. Moreover, the phytochemical composition of AEPL was identified in the present study. HepG2 cells treated with palmitic acid (PA) were used for exploring the effect of AEPL on lipid accumulation, apoptosis, ER stress, and antioxidant response. The chemical composition of AEPL was analyzed by HPLC-ESI-MS/MS. AEPL treatment reduced PA-induced ROS production and lipid accumulation. Further molecular results revealed that AEPL restored cytochrome c in mitochondria and decreased caspase 3 activity to cease apoptosis. In addition, AEPL in PA-stressed HepG2 cells significantly reduced the ER stress and suppressed SREBP-1 activation for decreasing lipogenesis. For defending PA-induced oxidative stress, AEPL promoted Nrf2 expression and its target genes, SOD1 and GPX3, expressions. The present study suggested that AEPL protected from PA-induced lipotoxicity through reducing ER stress, increasing antioxidant ability, and inhibiting apoptosis. The efficacy of AEPL on lipotoxicity was probably concerned with kaempferol and isorhamnetin derived compounds.

TetR-family transcriptional repressor Thermus thermophilus FadR controls fatty acid degradation

Microbiology ◽  
2011 ◽  
Vol 157 (6) ◽  
pp. 1589-1601 ◽  
Author(s):  
Yoshihiro Agari ◽  
Kazuko Agari ◽  
Keiko Sakamoto ◽  
Seiki Kuramitsu ◽  
Akeo Shinkai
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Target Genes ◽  
Thermus Thermophilus ◽  
Acyl Chain ◽  
Metabolic Energy ◽  
Straight Chain ◽  
Fatty Acid Degradation ◽  
Acid Degradation

In the extremely thermophilic bacterium Thermus thermophilus HB8, one of the four TetR-family transcriptional regulators, which we named T. thermophilus FadR, negatively regulated the expression of several genes, including those involved in fatty acid degradation, both in vivo and in vitro. T. thermophilus FadR repressed the expression of the target genes by binding pseudopalindromic sequences covering the predicted −10 hexamers of their promoters, and medium-to-long straight-chain (C10–18) fatty acyl-CoA molecules were effective for transcriptional derepression. An X-ray crystal structure analysis revealed that T. thermophilus FadR bound one lauroyl (C12)-CoA molecule per FadR monomer, with its acyl chain moiety in the centre of the FadR molecule, enclosed within a tunnel-like substrate-binding pocket surrounded by hydrophobic residues, and the CoA moiety interacting with basic residues on the protein surface. The growth of T. thermophilus HB8, with palmitic acid as the sole carbon source, increased the expression of FadR-regulated genes. These results indicate that in T. thermophilus HB8, medium-to-long straight-chain fatty acids can be used for metabolic energy under the control of FadR, although the major fatty acids found in this strain are iso- and anteiso-branched-chain (C15 and 17) fatty acids.

scholarly journals PPARα agonist fenofibrate enhances fatty acid β-oxidation and attenuates polycystic kidney and liver disease in mice

2018 ◽  
Vol 314 (1) ◽  
pp. F122-F131 ◽  
Author(s):  
Ronak Lakhia ◽  
Matanel Yheskel ◽  
Andrea Flaten ◽  
Ezekiel B. Quittner-Strom ◽  
William L. Holland ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Target Genes ◽  
Weight Ratio ◽  
Nuclear Hormone Receptor ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Preclinical Trial ◽  
Oxidation Rates ◽  
Fenofibrate Treatment ◽  
Pparα Agonist

Peroxisome proliferator-activated receptor α (PPARα) is a nuclear hormone receptor that promotes fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS). We and others have recently shown that PPARα and its target genes are downregulated, and FAO and OXPHOS are impaired in autosomal dominant polycystic kidney disease (ADPKD). However, whether PPARα and FAO/OXPHOS are causally linked to ADPKD progression is not entirely clear. We report that expression of PPARα and FAO/OXPHOS genes is downregulated, and in vivo β-oxidation rate of 3H-labeled triolein is reduced in Pkd1RC/RC mice, a slowly progressing orthologous model of ADPKD that closely mimics the human ADPKD phenotype. To evaluate the effects of upregulating PPARα, we conducted a 5-mo, randomized, preclinical trial by treating Pkd1RC/RC mice with fenofibrate, a clinically available PPARα agonist. Fenofibrate treatment resulted in increased expression of PPARα and FAO/OXPHOS genes, upregulation of peroxisomal and mitochondrial biogenesis markers, and higher β-oxidation rates in Pkd1RC/RC kidneys. MRI-assessed total kidney volume and total cyst volume, kidney-weight-to-body-weight ratio, cyst index, and serum creatinine levels were significantly reduced in fenofibrate-treated compared with untreated littermate Pkd1RC/RC mice. Moreover, fenofibrate treatment was associated with reduced kidney cyst proliferation and infiltration by inflammatory cells, including M2-like macrophages. Finally, fenofibrate treatment also reduced bile duct cyst number, cyst proliferation, and liver inflammation and fibrosis. In conclusion, our studies suggest that promoting PPARα activity to enhance mitochondrial metabolism may be a useful therapeutic strategy for ADPKD.

ATGL-mediated triglyceride turnover and the regulation of mitochondrial capacity in skeletal muscle

2015 ◽  
Vol 308 (11) ◽  
pp. E960-E970 ◽  
Author(s):  
Ruth C. R. Meex ◽  
Andrew J. Hoy ◽  
Rachael M. Mason ◽  
Sheree D. Martin ◽  
Sean L. McGee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Lipid Droplets ◽  
Target Genes ◽  
Control Point ◽  
Hormone Sensitive Lipase ◽  
Acid Oxidation ◽  
Minor Importance ◽  
Transcriptional Responses ◽  
Mitochondrial Capacity

Emerging evidence indicates that skeletal muscle lipid droplets are an important control point for intracellular lipid homeostasis and that regulating fatty acid fluxes from lipid droplets might influence mitochondrial capacity. We used pharmacological blockers of the major triglyceride lipases, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase, to show that a large proportion of the fatty acids that are transported into myotubes are trafficked through the intramyocellular triglyceride pool. We next tested whether increasing lipolysis from intramyocellular lipid droplets could activate transcriptional responses to enhance mitochondrial and fatty acid oxidative capacity. ATGL was overexpressed by adenoviral and adenoassociated viral infection in C2C12 myotubes and the tibialis anterior muscle of C57Bl/6 mice, respectively. ATGL overexpression in C2C12 myotubes increased lipolysis, which was associated with increased peroxisome proliferator-activated receptor (PPAR)-∂ activity, transcriptional upregulation of some PPAR∂ target genes, and enhanced mitochondrial capacity. The transcriptional responses were specific to ATGL actions and not a generalized increase in fatty acid flux in the myotubes. Marked ATGL overexpression (20-fold) induced modest molecular changes in the skeletal muscle of mice, but these effects were not sufficient to alter fatty acid oxidation. Together, these data demonstrate the importance of lipid droplets for myocellular fatty acid trafficking and the capacity to modulate mitochondrial capacity by enhancing lipid droplet lipolysis in vitro; however, this adaptive program is of minor importance when superimposing the normal metabolic stresses encountered in free-moving animals.

Regulation of the SREBP transcription factors by mTORC1

2011 ◽  
Vol 39 (2) ◽  
pp. 495-499 ◽  
Author(s):  
Caroline A. Lewis ◽  
Beatrice Griffiths ◽  
Claudio R. Santos ◽  
Mario Pende ◽  
Almut Schulze
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
De Novo ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Mammalian Target Of Rapamycin ◽  
Lipid Biosynthesis ◽  
De Novo Lipogenesis ◽  
Genes Encoding

In recent years several reports have linked mTORC1 (mammalian target of rapamycin complex 1) to lipogenesis via the SREBPs (sterol-regulatory-element-binding proteins). SREBPs regulate the expression of genes encoding enzymes required for fatty acid and cholesterol biosynthesis. Lipid metabolism is perturbed in some diseases and SREBP target genes, such as FASN (fatty acid synthase), have been shown to be up-regulated in some cancers. We have previously shown that mTORC1 plays a role in SREBP activation and Akt/PKB (protein kinase B)-dependent de novo lipogenesis. Our findings suggest that mTORC1 plays a crucial role in the activation of SREBP and that the activation of lipid biosynthesis through the induction of SREBP could be part of a regulatory pathway that co-ordinates protein and lipid biosynthesis during cell growth. In the present paper, we discuss the increasing amount of data supporting the potential mechanisms of mTORC1-dependent activation of SREBP as well as the implications of this signalling pathway in cancer.

scholarly journals Effects of ChREBP deficiency on adrenal lipogenesis and steroidogenesis

2021 ◽  
Author(s):  
Ken Takao ◽  
Katsumi Iizuka ◽  
Yanyan Liu ◽  
Teruaki Sakurai ◽  
Sodai Kubota ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Target Genes ◽  
Adrenal Glands ◽  
Plasma Cholesterol ◽  
Steroid Hormone ◽  
Acid Synthesis ◽  
Cholesterol Content ◽  
Hormone Synthesis ◽  
Corticosterone Secretion ◽  
Element Binding Protein

Carbohydrate response element binding protein (ChREBP) is critical in the regulation of fatty acid and triglyceride synthesis in the liver. Interestingly, Chrebp-/- mice show reduced levels of plasma cholesterol, which is critical for steroid hormone synthesis in adrenal glands. Furthermore, Chrebp mRNA expression was previously reported in human adrenal glands. Thus, it remains to be investigated whether ChREBP plays a role directly or indirectly in steroid hormone synthesis and release in adrenal glands. In the present study, we find that Chrebp mRNA is expressed in mouse adrenal glands and that ChREBP binds to carbohydrate response elements. Histological analysis of Chrebp-/- mice shows no adrenal hyperplasia and less oil red O staining compared with that in wild-type mice. In adrenal glands of Chrebp-/- mice, expression of Fasn and Scd1, two enzymes critical for fatty acid synthesis, was substantially lower and triglyceride content was reduced. Expression of Srebf2, a key transcription factor controlling synthesis and uptake of cholesterol and the target genes was upregulated, while cholesterol content was not significantly altered in the adrenal glands of Chrebp-/- mice. Adrenal corticosterone content and plasma adrenocorticotropic hormone and corticosterone levels were not significantly altered in Chrebp-/- mice. Consistently, expression of genes related to steroid hormone synthesis was not altered. Corticosterone secretion in response to two different stimuli, namely 24-h starvation and cosyntropin administration, were also not altered in Chrebp-/- mice. Taking these results together, corticosterone synthesis and release were not affected in Chrebp-/- mice despite reduced plasma cholesterol levels.

scholarly journals Promoter-Specific Roles for Liver X Receptor/Corepressor Complexes in the Regulation of ABCA1 and SREBP1 Gene Expression

2003 ◽  
Vol 23 (16) ◽  
pp. 5780-5789 ◽  
Author(s):  
Brandee L. Wagner ◽  
Annabel F. Valledor ◽  
Gang Shao ◽  
Chris L. Daige ◽  
Eric D. Bischoff ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Hormone Receptors ◽  
Target Genes ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Whole Body ◽  
Abca1 Gene ◽  
Element Binding Protein ◽  
X Receptors

ABSTRACT Liver X receptors (LXRs) regulate the expression of genes involved in cholesterol and fatty acid homeostasis, including the genes for ATP-binding cassette transporter A1 (ABCA1) and sterol response element binding protein 1 (SREBP1). Loss of LXR leads to derepression of the ABCA1 gene in macrophages and the intestine, while the SREBP1c gene remains transcriptionally silent. Here we report that high-density-lipoprotein (HDL) cholesterol levels are increased in LXR-deficient mice, suggesting that derepression of ABCA1 and possibly other LXR target genes in selected tissues is sufficient to result in enhanced HDL biogenesis at the whole-body level. We provide several independent lines of evidence indicating that the repressive actions of LXRs are dependent on interactions with the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoic acid and thyroid hormone receptors (SMRT). While dissociation of NCoR and SMRT results in derepression of the ABCA1 gene in macrophages, it is not sufficient for derepression of the SREBP1c gene. These findings reveal differential requirements for corepressors in the regulation of genes involved in cholesterol and fatty acid homeostasis and raise the possibility that these interactions may be exploited to develop synthetic ligands that selectively modulate LXR actions in vivo.

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