scholarly journals Transcriptome analysis of the liver of Eospalax fontanierii under hypoxia

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11166
Author(s):  
Zhiqiang Hao ◽  
Lulu Xu ◽  
Li Zhao ◽  
Jianping He ◽  
Guanglin Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cell Damage ◽  
Expression Patterns ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Subterranean Rodents ◽  
Sprague Dawley ◽  
Subterranean Rodent ◽  
Hypoxia Adaptation ◽  
Ppar Signaling

Hypoxia can induce cell damage, inflammation, carcinogenesis, and inhibit liver regeneration in non-adapted species. Because of their excellent hypoxia adaptation features, subterranean rodents have been widely studied to clarify the mechanism of hypoxia adaptation. Eospalax fontanierii, which is a subterranean rodent found in China, can survive for more than 10 h under 4% O2 without observable injury, while Sprague-Dawley rats can survive for less than 6 h under the same conditions. To explore the potential mechanism of hypoxia responses in E. fontanierii, we performed RNA-seq analysis of the liver in E. fontanierii exposed to different oxygen levels (6.5% 6h, 10.5% 44h, and 21%). Based on the bioinformatics analysis, 39,439 unigenes were assembled, and 56.78% unigenes were annotated using public databases (Nr, GO, Swiss-Prot, KEGG, and Pfam). In total, 725 differentially expressed genes (DEGs) were identified in the response to hypoxia; six with important functions were validated by qPCR. Those DEGs were mainly involved in processes related to lipid metabolism, steroid catabolism, glycolysis/gluconeogenesis, and the AMPK and PPAR signaling pathway. By analyzing the expression patterns of important genes related to energy associated metabolism under hypoxia, we found that fatty acid oxidation and gluconeogenesis were increased, while protein synthesis and fatty acid synthesis were decreased. Furthermore, the upregulated expression of specific genes with anti-apoptosis or anti-oxidation functions under hypoxia may contribute to the mechanism by which E. fontanierii tolerates hypoxia. Our results provide an understanding of the response to hypoxia in E. fontanierii, and have potential value for biomedical studies.

scholarly journals Transcriptome Analysis of the Liver of Eospalax Fontanierii Under Hypoxia

2020 ◽  
Author(s):  
Zhiqiang Hao ◽  
Lulu Xu ◽  
Jianping He ◽  
Guanglin Li ◽  
Jingang Li
Keyword(s):  
Fatty Acid ◽  
Cell Damage ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Acid Oxidation ◽  
Subterranean Rodents ◽  
Subterranean Rodent ◽  
Oxygen Levels ◽  
Hypoxia Adaptation

Abstract BackgroundHypoxia can induce cell damage, inflammation, carcinogenesis, and inhibit liver regeneration in non-adapted species. Because of their excellent hypoxia adaptation features, subterranean rodents have been widely studied to clarify the mechanism of hypoxia adaptation. Eospalax fontanierii, which is a subterranean rodent found in China, can survive for more than 10 h under 4% O2 without observable injury, while Sprague-Dawle rats can survive for less than 6 h under the same conditions. To explore the potential mechanism of hypoxia adaptation in E. fontanierii, we performed RNA-seq analysis of the liver in E. fontanierii exposed to different oxygen levels (6.5%, 10.5%, and 21%).ResultsBased on the bioinformatics analysis, 39,439 unigenes were assembled, and 56.78% unigenes were annotated using public databases (Nr, GO, Swiss-Prot, KEGG, and Pfam). In total, 725 differentially expressed genes (DEGs) were identified in the response to hypoxia; six with important functions were validated by qPCR. Those DEGs were mainly involved in processes related to lipid metabolism, steroid catabolism, glycolysis/gluconeogenesis, and the AMPK and PPAR signaling pathway. By analyzing the expression patterns of hub genes related to energy associated metabolism under hypoxia, we found that fatty acid oxidation and gluconeogenesis were increased, while protein synthesis and fatty acid synthesis were decreased. ConclusionsWe characterized the E. fontanierii liver transcriptomes and profiled the changes in gene expression in the liver under different oxygen levels. Functional enrichment analysis showed that the main functions (steroid catabolic process, lipid metabolic process, primary bile acid biosynthesis, energy production and amino acid metabolic) of the liver were regulated in response to hypoxia. We identified multiple important DEGs underlying the potential molecular adaptation mechanisms to hypoxia, including genes associated with anti-apoptosis, energy supply, anti-inflammation, and anti-oxidation. Our results provide a comprehensive understanding of the response to hypoxia in E. fontanierii, and have potential value for biomedical studies.

scholarly journals High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta

2013 ◽  
Vol 305 (2) ◽  
pp. E205-E212 ◽  
Author(s):  
Francisco Visiedo ◽  
Fernando Bugatto ◽  
Viviana Sánchez ◽  
Irene Cózar-Castellano ◽  
Jose L. Bartha ◽  
...  
Keyword(s):  
Fatty Acid ◽  
High Glucose ◽  
De Novo ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Glucose Levels ◽  
Triglyceride Accumulation ◽  
Triglyceride Content ◽  
Low Glucose ◽  
Cpt I

Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ∼30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ∼20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ∼40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ∼70% and phosphorylation levels of acetyl-CoA carboxylase by ∼25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides.

scholarly journals Expression patterns of major genes in fatty acid synthesis, inflammation, oxidative stress pathways from colostrum to milk in Damascus goats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akın Yakan ◽  
Hüseyin Özkan ◽  
Baran Çamdeviren ◽  
Ufuk Kaya ◽  
İrem Karaaslan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Transition Period ◽  
Freezing Point ◽  
Expression Patterns ◽  
Acid Synthesis ◽  
Major Genes ◽  
Genes Expression ◽  
And Oxidative Stress

AbstractThe molecular regulation of milk secretion and quality in the transition period from colostrum to milk in goats is largely unknown. In the present study, mammary gland secretion of goats was collected in 0th, 4th, 7th, 14th and 28th days after parturition. In addition to composition and fatty acid profile of colostrum or milk, FASN, SCD, ACACA, COX-2, NRF2, TLR2, NF-kB, LTF and PTX3 genes expression patterns were determined from milk somatic cells. While somatic cell count (SCC), malondialdehyde (MDA), fat, fat-free dry matter, protein and lactose were highest as expression levels of the oxidative and inflammatory genes, freezing point and electrical conductivity were lowest in colostrum. With the continuation of lactation, most of the fatty acids, n3 ratio, and odour index increased but C14:0 and C16:0 decreased. While FASN was upregulated almost threefolds in 14th day, ACACA was upregulated more than fivefolds in 7th and 14th days. Separately, the major genes in fatty acid synthesis, inflammation and oxidative stress were significantly associated with each other due to being positively correlated. MDA was positively correlated with SCC and some of the genes related inflammation and oxidative stress. Furthermore, significant negative correlations were determined between SCC and fatty acid synthesis related genes. With this study, transition period of mammary secretion was particularly clarified at the molecular levels in Damascus goats.

Fatty acid oxidation and triacylglycerol hydrolysis are enhanced after chronic leptin treatment in rats

2002 ◽  
Vol 282 (3) ◽  
pp. E593-E600 ◽  
Author(s):  
Gregory R. Steinberg ◽  
Arend Bonen ◽  
David J. Dyck
Keyword(s):  
Fatty Acid ◽  
Citrate Synthase ◽  
Uncoupling Protein ◽  
Oxidative Capacity ◽  
Hormone Sensitive Lipase ◽  
Acid Oxidation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Triacylglycerol Hydrolysis ◽  
Hormone Sensitive

Leptin acutely increases fatty acid (FA) oxidation and triacylglycerol (TG) hydrolysis and decreases TG esterification in oxidative rodent muscle. However, the effects of chronic leptin administration on FA metabolism in skeletal muscle have not been examined. We hypothesized that chronic leptin treatment would enhance TG hydrolysis as well as the capacity to oxidize FA in soleus (SOL) muscle. Female Sprague-Dawley rats were infused for 2 wk with leptin (LEPT; 0.5 mg · kg−1 · day−1) by use of subcutaneously implanted miniosmotic pumps. Control (AD-S) and pair-fed (PF-S) animals received saline-filled implants. Subsequently, FA metabolism was monitored for 45 min in isolated, resting, and contracting (20 tetani/min) SOL muscles by means of pulse-chase procedures. Food intake (−33 ± 2%, P < 0.01) and body mass (−12.5 ± 4%, P = 0.01) were reduced in both LEPT and PF-S animals. Leptin levels were elevated (+418 ± 7%, P < 0.001) in treated animals but reduced in PF-S animals (−73 ± 8%, P< 0.05) relative to controls. At rest, TG hydrolysis was increased in leptin-treated rats (1.8 ± 2.2, AD-S vs. 23.5 ± 8.1 nmol/g wet wt, LEPT; P < 0.001). In contracting SOL muscles, TG hydrolysis (1.5 ± 0.6, AD-S vs. 3.6 ± 1.0 μmol/g wet wt, LEPT; P = 0.02) and palmitate oxidation (18.3 ± 6.7, AD-S vs. 45.7 ± 9.9 nmol/g wet wt, LEPT; P < 0.05) were both significantly increased by leptin treatment. Chronic leptin treatment had no effect on TG esterification either at rest or during contraction. Markers of overall (citrate synthase) and FA (hydroxyacyl-CoA dehydrogenase) oxidative capacity were unchanged with leptin treatment. Protein expression of hormone-sensitive lipase (HSL) was also unaltered following leptin treatment. Thus leptin-induced increases in lipolysis are likely due to HSL activation (i.e., phosphorylation). Increased FA oxidation secondary to chronic leptin treatment is not due to an enhanced oxidative capacity and may be a result of enhanced flux into the mitochondrion (i.e., carnitine palmitoyltransferase I regulation) or electron transport uncoupling (i.e., uncoupling protein-3 expression).

scholarly journals Chronic Hypoxia Enhances β-Oxidation-Dependent Electron Transport via Electron Transferring Flavoproteins

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 172 ◽  
Author(s):  
Dominik C. Fuhrmann ◽  
Catherine Olesch ◽  
Nina Kurrle ◽  
Frank Schnütgen ◽  
Sven Zukunft ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Fatty Acid ◽  
Electron Transport ◽  
Mitochondrial Respiration ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Fatty Acid Production ◽  
Consumption Rates

Hypoxia poses a stress to cells and decreases mitochondrial respiration, in part by electron transport chain (ETC) complex reorganization. While metabolism under acute hypoxia is well characterized, alterations under chronic hypoxia largely remain unexplored. We followed oxygen consumption rates in THP-1 monocytes during acute (16 h) and chronic (72 h) hypoxia, compared to normoxia, to analyze the electron flows associated with glycolysis, glutamine, and fatty acid oxidation. Oxygen consumption under acute hypoxia predominantly demanded pyruvate, while under chronic hypoxia, fatty acid- and glutamine-oxidation dominated. Chronic hypoxia also elevated electron-transferring flavoproteins (ETF), and the knockdown of ETF–ubiquinone oxidoreductase lowered mitochondrial respiration under chronic hypoxia. Metabolomics revealed an increase in citrate under chronic hypoxia, which implied glutamine processing to α-ketoglutarate and citrate. Expression regulation of enzymes involved in this metabolic shunting corroborated this assumption. Moreover, the expression of acetyl-CoA carboxylase 1 increased, thus pointing to fatty acid synthesis under chronic hypoxia. Cells lacking complex I, which experienced a markedly impaired respiration under normoxia, also shifted their metabolism to fatty acid-dependent synthesis and usage. Taken together, we provide evidence that chronic hypoxia fuels the ETC via ETFs, increasing fatty acid production and consumption via the glutamine-citrate-fatty acid axis.

scholarly journals Proteomics study of the effect of high-fat diet on rat liver

2019 ◽  
Vol 122 (9) ◽  
pp. 1062-1072 ◽  
Author(s):  
Jian Sang ◽  
Hengxian Qu ◽  
Ruixia Gu ◽  
Dawei Chen ◽  
Xia Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Rat Liver ◽  
High Fat Diet ◽  
Acid Synthesis ◽  
High Energy ◽  
The Body ◽  
Acid Oxidation ◽  
High Fat ◽  
Bioinformatics Analyses ◽  
Fat Diets

AbstractExcessive intake of high-energy diets is an important cause of most obesity. The intervention of rats with high-fat diet can replicate the ideal animal model for studying the occurrence of human nutritional obesity. Proteomics and bioinformatics analyses can help us to systematically and comprehensively study the effect of high-fat diet on rat liver. In the present study, 4056 proteins were identified in rat liver by using tandem mass tag. A total of 198 proteins were significantly changed, of which 103 were significantly up-regulated and ninety-five were significantly down-regulated. These significant differentially expressed proteins are primarily involved in lipid metabolism and glucose metabolism processes. The intake of a high-fat diet forces the body to maintain physiological balance by regulating these key protein spots to inhibit fatty acid synthesis, promote fatty acid oxidation and accelerate fatty acid degradation. The present study enriches our understanding of metabolic disorders induced by high-fat diets at the protein level.

scholarly journals Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats

2016 ◽  
Vol 113 (13) ◽  
pp. E1796-E1805 ◽  
Author(s):  
Geraldine Harriman ◽  
Jeremy Greenwood ◽  
Sathesh Bhat ◽  
Xinyi Huang ◽  
Ruiying Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthesis ◽  
Fatty Liver Disease ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase

Simultaneous inhibition of the acetyl-CoA carboxylase (ACC) isozymes ACC1 and ACC2 results in concomitant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation and may favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver disease. Using structure-based drug design, we have identified a series of potent allosteric protein–protein interaction inhibitors, exemplified by ND-630, that interact within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit the enzymatic activity of both ACC isozymes, reduce fatty acid synthesis and stimulate fatty acid oxidation in cultured cells and in animals, and exhibit favorable drug-like properties. When administered chronically to rats with diet-induced obesity, ND-630 reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia. When administered chronically to Zucker diabetic fatty rats, ND-630 reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c (0.9% reduction). Together, these data suggest that ACC inhibition by representatives of this series may be useful in treating a variety of metabolic disorders, including metabolic syndrome, type 2 diabetes mellitus, and fatty liver disease.

Fatty acid synthesis: from CO2 to functional genomics

2000 ◽  
Vol 28 (6) ◽  
pp. 567-574 ◽  
Author(s):  
J. Ohlrogge ◽  
M. Pollard ◽  
X. Bao ◽  
M. Focke ◽  
T. Girke ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Regulatory Networks ◽  
Fatty Acid Synthase ◽  
Expression Patterns ◽  
Acid Synthesis ◽  
Acetyl Coa ◽  
Specific Expression ◽  
Direct Production

For over 25 years there has been uncertainty over the pathway from CO2, to acetyl-CoA in chloroplasts. On the one hand, free acetate is the most effective substrate for fatty acid synthesis by isolated chloroplasts, and free acetate concentrations reported in leaf tissue (0.1–1 mM) appear adequate to saturate fatty acid synthase. On the other hand, a clear mechanism to generate sufficient free acetate for fatty acid synthesis is not established and direct production of acetyl-CoA from pyruvate by a plastid pyruvate dehydrogenase seems a more simple and direct path. We have re-examined this question and attempted to distinguish between the alternatives. The kinetics of 13CO2 and 14CO2 movement into fatty acids and the absolute rate of fatty acid synthesis in leaves was determined in light and dark. Because administered 14C appears in fatty acids within < 2–3 min our results are inconsistent with a large pool of free acetate as an intermediate in leaf fatty acid synthesis. In addition, these studies provide an estimate of the turnover rate of fatty acid in leaves. Studies similar to the above are more complex in seeds, and some questions about the regulation of plant lipid metabolism seem difficult to solve using conventional biochemical or molecular approaches. For example, we have little understanding of why or how some seeds produce >50%, oil whereas other seeds store largely carbohydrate or protein. Major control over complex plant biochemical pathways may only become possible by understanding regulatory networks which provide ‘global’ control over these pathways. To begin to discover such networks and provide a broad analysis of gene expression in developing oilseeds, we have produced micro-arrays that display approx. 5000 seed-expressed Arabidopsis genes. Sensitivity of the arrays was 1–2 copies of mRNA/cell. The arrays have been hybridized with probes derived from seeds, leaves and roots, and analysis of expression ratios between the different tissues has allowed the tissue-specific expression patterns of many hundreds of genes to be described for the first time. Approx. 10% of the genes were expressed at ratios ≥ 10-fold higher in seeds than in leaves or roots. Included in this list are a large number of proteins of unknown function, and potential regulatory factors such as protein kinases, phosphatases and transcription factors. The arrays were also found to be useful for analysis of Brassica seeds.

Regulation of mammalian acetyl-CoA carboxylase

2002 ◽  
Vol 30 (6) ◽  
pp. 1059-1064 ◽  
Author(s):  
M. R. Munday
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Critical Role ◽  
Physiological Role ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase

Acetyl-CoA carboxylase (ACC) plays a critical role in the regulation of fatty acid metabolism and its two isoforms, ACCα and ACCβ, appear to have distinct functions in the control of fatty acid synthesis and fatty acid oxidation, respectively. They are regulated by similar short-term mechanisms of allosteric activation by citrate, and reversible phosphorylation and inactivation, and there is clearly interaction between these mechanisms. AMP-activated protein kinase is the important physiological ACC kinase for both isoforms and yet there is a potential physiological role for cAMP-dependent protein kinase in the hormonally mediated inactivation of ACCα, and phosphorylation of ACCβ in its unique N-terminus.

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