Functional Analysis of Lipid Metabolism in Magnaporthe grisea Reveals a Requirement for Peroxisomal Fatty Acid β-Oxidation During Appressorium-Mediated Plant Infection

The rice blast fungus Magnaporthe grisea infects plants by means of specialized infection structures known as appressoria. Turgor generated in the appressorium provides the invasive force that allows the fungus to breach the leaf cuticle with a narrow-penetration hypha gaining entry to the underlying epidermal cell. Appressorium maturation in M. grisea involves mass transfer of lipid bodies to the developing appressorium, coupled to autophagic cell death in the conidium and rapid lipolysis at the onset of appressorial turgor generation. Here, we report identification of the principal components of lipid metabolism in M. grisea based on genome sequence analysis. We show that deletion of any of the eight putative intracellular triacylglycerol lipase-encoding genes from the fungus is insufficient to prevent plant infection, highlighting the complexity and redundancy associated with appressorial lipolysis. In contrast, we demonstrate that a peroxisomally located multifunctional, fatty acid β-oxidation enzyme is critical to appressorium physiology, and blocking peroxisomal biogenesis prevents plant infection. Taken together, our results indicate that, although triacylglycerol breakdown in the appressorium involves the concerted action of several lipases, fatty acid metabolism and consequent generation of acetyl CoA are necessary for M. grisea to complete its prepenetration phase of development and enter the host plant.

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

BMC Genomics ◽

10.1186/s12864-019-6116-0 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 8

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.

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MicroRNAs and their regulatory networks in Chinese Gushi chicken abdominal adipose tissue during postnatal late development

BMC Genomics ◽

10.1186/s12864-019-6094-2 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Yi Chen ◽

Yinli Zhao ◽

Wenjiao Jin ◽

Yuanfang Li ◽

Yanhua Zhang ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Lipid Metabolism ◽

Small Rna ◽

Acid Metabolism ◽

Abdominal Fat ◽

Interaction Networks ◽

Late Development ◽

Abdominal Adipose Tissue ◽

Adipose Tissue Development

Abstract Background Abdominal fat is the major adipose tissue in chickens. The growth status of abdominal fat during postnatal late development ultimately affects meat yield and quality in chickens. MicroRNAs (miRNAs) are endogenous small noncoding RNAs that regulate gene expression at the post-transcriptional level. Studies have shown that miRNAs play an important role in the biological processes involved in adipose tissue development. However, few studies have investigated miRNA expression profiles and their interaction networks associated with the postnatal late development of abdominal adipose tissue in chickens. Results We constructed four small RNA libraries from abdominal adipose tissue obtained from Chinese domestic Gushi chickens at 6, 14, 22, and 30 weeks. A total of 507 known miRNAs and 53 novel miRNAs were identified based on the four small RNA libraries. Fifty-one significant differentially expressed (SDE) miRNAs were identified from six combinations by comparative analysis, and the expression patterns of these SDE miRNAs were divided into six subclusters by cluster analysis. Gene ontology enrichment analysis showed that the SDE miRNAs were primarily involved in the regulation of fat cell differentiation, regulation of lipid metabolism, regulation of fatty acid metabolism, and unsaturated fatty acid metabolism in the lipid metabolism- or deposition-related biological process categories. In addition, we constructed differentially expressed miRNA–mRNA interaction networks related to abdominal adipose development. The results showed that miRNA families, such as mir-30, mir-34, mir-199, mir-8, and mir-146, may have key roles in lipid metabolism, adipocyte proliferation and differentiation, and cell junctions during abdominal adipose tissue development in chickens. Conclusions This study determined the dynamic miRNA transcriptome and characterized the miRNA–mRNA interaction networks in Gushi chicken abdominal adipose tissue for the first time. The results expanded the number of known miRNAs in abdominal adipose tissue and provide novel insights and a valuable resource to elucidate post-transcriptional regulation mechanisms during postnatal late development of abdominal adipose tissue in chicken.

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Lipid Metabolism Profiles in Rheumatic Diseases

Frontiers in Pharmacology ◽

10.3389/fphar.2021.643520 ◽

2021 ◽

Vol 12 ◽

Author(s):

Weilin Chen ◽

Qi Wang ◽

Bin Zhou ◽

Lihua Zhang ◽

Honglin Zhu

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Rheumatic Diseases ◽

Fatty Acid Metabolism ◽

High Mortality ◽

Acid Metabolism ◽

Cell Metabolism ◽

Therapeutic Strategies ◽

Clinical Applications ◽

Multiple Organs

Rheumatic diseases are a group of chronic autoimmune disorders that involve multiple organs or systems and have high mortality. The mechanisms of these diseases are still ill-defined, and targeted therapeutic strategies are still challenging for physicians. Recent research indicates that cell metabolism plays important roles in the pathogenesis of rheumatic diseases. In this review, we mainly focus on lipid metabolism profiles (dyslipidaemia, fatty acid metabolism) and mechanisms in rheumatic diseases and discuss potential clinical applications based on lipid metabolism profiles.

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Multi-Omics Analysis of Fatty Acid Metabolism in Thyroid Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.737127 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jinghui Lu ◽

Yankun Zhang ◽

Min Sun ◽

Changyuan Ding ◽

Lei Zhang ◽

...

Keyword(s):

Thyroid Cancer ◽

Fatty Acid ◽

Lipid Metabolism ◽

Thyroid Carcinoma ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Metabolic Reprogramming ◽

Clinical Samples ◽

Integrated Analysis ◽

Additional Energy

ObjectivePapillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancer and affects a large number of individuals. The pathogenesis of PTC has not been completely elucidated thus far. Metabolic reprogramming is a common feature in tumours. Our previous research revealed the reprogramming of lipid metabolism in PTC. Further studies on lipid metabolism reprogramming may help elucidate the pathogenesis of PTC.MethodsClinical samples of PTC and para-tumour tissue were analysed using lipidomic, proteomic, and metabolomic approaches. A multi-omics integrative strategy was adopted to identify the important pathways in PTC. The findings were further confirmed using western blotting, tissue microarray, bioinformatics, and cell migration assays.ResultsMulti-omics data and the results of integrated analysis revealed that the three steps of fatty acid metabolism (hydrolysis, transportation, and oxidation) were significantly enhanced in PTC. Especially, the expression levels of LPL, FATP2, and CPT1A, three key enzymes in the respective steps, were elevated in PTC. Moreover, LPL, FATP2 and CPT1A expression was associated with the TNM stage, lymph node metastasis of PTC. Moreover, high levels of FATP2 and CPT1A contributed to poor prognosis of PTC. In addition, ectopic overexpression of LPL, FATP2 and CPT1A can each promote the migration of thyroid cancer cells.ConclusionsOur data suggested that enhanced fatty acid metabolism supplied additional energy and substrates for PTC progression. This may help elucidating the underlying mechanism of PTC pathogenesis and identifying the potential therapeutic targets for PTC.

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Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer

Nature Communications ◽

10.1038/s41467-021-24656-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Li-Yan Li ◽

Qian Yang ◽

Yan-Yi Jiang ◽

Wei Yang ◽

Yuan Jiang ◽

...

Keyword(s):

Transcription Factor ◽

Fatty Acid ◽

Lipid Metabolism ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Human Cancer ◽

Regulatory Element ◽

Regulatory Elements ◽

Gene Set Enrichment Analysis ◽

Transcriptional Dysregulation

AbstractSquamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.

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Effects of Plant Sterols Intake on Systematic and Tissue Specific Lipid Metabolism in C57BL/6J Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzab037_098 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 388-388

Author(s):

Qian Zhu ◽

Jingjing Wu ◽

Daxue He ◽

Xuemei Lian

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Plant Sterols ◽

Differentially Expressed ◽

Rna Seq ◽

Tissue Specific ◽

Free Sterols ◽

Specific Lipid

Abstract Objectives To investigate the effects of plant sterols intake on systematic and tissue specific lipid metabolism in C57BL/6J mice. Methods Male C57BL/6J mice were randomly divided into control diet group (CS) and plant sterol group (PS, 2% plant sterols). After 28 weeks of continuous feeding, the serum of the mice were collected for biochemical and mass spectrometry tests. Serum levels of total cholesterol (TC), triglyceride (TG) and free sterols were determined. The livers and lungs were collected for free sterol quantification and RNA-seq analysis. Results Compared with the CS group, 2% plant sterols intake significantly reduced the levels of TC in the serum of mice (P < 0.05), with the TG level unchanged. The quantitative results of free sterols showed that the concentration of campesterol were increased, and the cholestanol levels were decreased significantly in the serum and liver of the PS group mice. The results of RNA-seq analysis were used to further evaluate its impact on the lipid metabolism related gene expression profile in the livers and lungs. The results showed that HMGCR, SQLE, HMGCS1, SREBF1, and other genes related to cholesterol synthesis in the PS group were significantly up-regulated in the liver, but not in the lung; Among the first 20 targeting pathways related to the action of plant sterols, the liver differentially expressed genes were enriched in lipid metabolism (steroid biosynthesis, terpenoid skeleton biosynthesis, peroxisome, bile acid secretion, PPAR, MAPK, fatty acid metabolism.), inflammation related (Cell adhesion molecules, leukocyte trans-endothelial migration) and amino acid metabolism (glutathione, valine, leucine and isoleucine metabolism). The differential genes in lung tissue are enriched in lipid metabolism (acetone metabolism, fatty acid metabolism, insulin resistance, terpenoid skeleton biosynthesis, iron death, PPAR), cell function (internal Swallowing, aging) and vascular smooth muscle contraction etc. Conclusions Differentially expressed gene networks reflect the multi-dimensional regulation of plant sterols on tissue specific lipid metabolism, which lays a good foundation for further revealing its mechanism. Funding Sources Yihaikerry Nutrition and Food Safety Foundation, Chinese Nutrition Society; Project of Technology Innovation and Application, Chongqing, China

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Roles of Vitamin A Metabolism in the Development of Hepatic Insulin Resistance

ISRN Hepatology ◽

10.1155/2013/534972 ◽

2013 ◽

Vol 2013 ◽

pp. 1-21 ◽

Cited By ~ 8

Author(s):

Guoxun Chen

Keyword(s):

Insulin Resistance ◽

Transcription Factors ◽

Retinoic Acid ◽

Fatty Acid ◽

Lipid Metabolism ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Hepatic Insulin Resistance ◽

Glucose And Lipid Metabolism ◽

Hepatic Genes

The increase in the number of people with obesity- and noninsulin-dependent diabetes mellitus has become a major public health concern. Insulin resistance is a common feature closely associated with human obesity and diabetes. Insulin regulates metabolism, at least in part, via the control of the expression of the hepatic genes involved in glucose and fatty acid metabolism. Insulin resistance is always associated with profound changes of the expression of hepatic genes for glucose and lipid metabolism. As an essential micronutrient, vitamin A (VA) is needed in a variety of physiological functions. The active metablite of VA, retinoic acid (RA), regulates the expression of genes through the activation of transcription factors bound to the RA-responsive elements in the promoters of RA-targeted genes. Recently, retinoids have been proposed to play roles in glucose and lipid metabolism and energy homeostasis. This paper summarizes the recent progresses in our understanding of VA metabolism in the liver and of the potential transcription factors mediating RA responses. These transcription factors are the retinoic acid receptor, the retinoid X receptor, the hepatocyte nuclear factor 4α, the chicken ovalbumin upstream promoter-transcription factor II, and the peroxisome proliferator-activated receptor β/δ. This paper also summarizes the effects of VA status and RA treatments on the glucose and lipid metabolism in vivo and the effects of retinoid treatments on the expression of insulin-regulated genes involved in the glucose and fatty acid metabolism in the primary hepatocytes. I discuss the roles of RA production in the development of insulin resistance in hepatocytes and proposes a mechanism by which RA production may contribute to hepatic insulin resistance. Given the large amount of information and progresses regarding the physiological functions of VA, this paper mainly focuses on the findings in the liver and hepatocytes and only mentions the relative findings in other tissues and cells.

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Animal biosynthesis of complex polyketides in a photosynthetic partnership

10.1101/764225 ◽

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.

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RiboTag translatomic profiling of Drosophila oenocytes under aging and oxidative stress

10.1101/272179 ◽

2018 ◽

Author(s):

Kerui Huang ◽

Wenhao Chen ◽

Fang Zhu ◽

Hua Bai

Keyword(s):

Oxidative Stress ◽

Fatty Acid ◽

Lipid Metabolism ◽

Stress Response ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Fat Body ◽

Mapk Signaling ◽

Age Related ◽

And Oxidative Stress

AbstractBackgroundAging is accompanied with loss of tissue homeostasis and accumulation of cellular damages. As one of the important metabolic centers, aged liver shows altered lipid metabolism, impaired detoxification pathway, increased inflammation and oxidative stress response. However, the mechanisms for these age-related changes still remain unclear. In fruit flies, Drosophila melanogaster, liver-like functions are controlled by two distinct tissues, fat body and oenocytes. Although the role of fat body in aging regulation has been well studied, little is known about how oenocytes age and what are their roles in aging regulation. To address these questions, we used cell-type-specific ribosome profiling (RiboTag) to study the impacts of aging and oxidative stress on oenocyte translatome in Drosophila.ResultsWe show that aging and oxidant paraquat significantly increased the levels of reactive oxygen species (ROS) in adult oenocytes of Drosophila, and aged oenocytes exhibited reduced sensitivity to paraquat treatment. Through RiboTag sequencing, we identified 3324 and 949 differentially expressed genes in oenocytes under aging and paraquat treatment, respectively. Aging and paraquat exhibit both shared and distinct regulations on oenocyte translatome. Among all age-regulated genes, mitochondrial, proteasome, peroxisome, fatty acid metabolism, and cytochrome P450 pathways were down-regulated, whereas DNA replication and glutathione metabolic pathways were up-regulated. Interestingly, most of the peroxisomal genes were down-regulated in aged oenocytes, including peroxisomal biogenesis factors and beta-oxidation genes. Further analysis of the oenocyte translatome showed that oenocytes highly expressed genes involving in liver-like processes (e.g., ketogenesis). Many age-related transcriptional changes in oenocytes are similar to aging liver, including up-regulation of Ras/MAPK signaling pathway and down-regulation of peroxisome and fatty acid metabolism.ConclusionsOur oenocyte-specific translatome analysis identified many genes and pathways that are shared between Drosophila oenocytes and mammalian liver, highlighting the molecular and functional similarities between the two tissues. Many of these genes are altered in both aged oenocytes and aged liver, suggesting a conserved molecular mechanism underlying oenocyte and liver aging. Thus, our translatome analysis will contribute significantly to the understanding of oenocyte biology, and its role in lipid metabolism, stress response and aging regulation.

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