Metabolomics analysis reveals the role of oxygen control in the nitrogen limitation induced lipid accumulation in Mortierella alpina

ABSTRACT Blastobotrys raffinosifermentans is an ascomycetous yeast with biotechnological applications, recently shown to be an oleaginous yeast accumulating lipids under nitrogen limitation. Diacylglycerol acyltransferases (DGATs) act in the lipid storage pathway, in the last step of triacylglycerol biosynthesis. Two DGAT families are widespread in eukaryotes. We first checked that B. raffinosifermentans strain LS3 possessed both types of DGAT, and we then overexpressed the native DGAT-encoding genes, DGA1 and DGA2, separately or together. DGA2 (from the DGAT1 family) overexpression was sufficient to increase lipid content significantly in LS3, to up to 26.5% of dry cell weight (DCW), 1.6 times the lipid content of the parental strain (16.90% of DCW) in glucose medium under nitrogen limitation. By contrast, DGA1 (of the DGAT2 type) overexpression led to a large increase (up to 140-fold) in the amount of the corresponding transcript, but had no effect on overall lipid content relative to the parental strain. Analysis of the expression of the native genes over time in the parental strain revealed that DGA2 transcript levels quadrupled between 8 and 24 h in the N-limited lipogenic medium, whereas DGA1 transcript levels remained stable. This survey highlights the predominant role of the DGAT1 family in lipid accumulation and demonstrates the suitability of B. raffinosifermentans for engineering for lipid production.

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The role of malic enzyme in the regulation of lipid accumulation in filamentous fungi

Microbiology ◽

10.1099/13500872-145-8-1911 ◽

1999 ◽

Vol 145 (8) ◽

pp. 1911-1917 ◽

Cited By ~ 147

Author(s):

James P. Wynn ◽

Aidil bin Abdul Hamid ◽

Colin Ratledge

Keyword(s):

Filamentous Fungi ◽

Lipid Accumulation ◽

Malic Enzyme

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The Role of Lipids, Lipid Metabolism and Ectopic Lipid Accumulation in Axon Growth, Regeneration and Repair after CNS Injury and Disease

Cells ◽

10.3390/cells10051078 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1078

Author(s):

Debasish Roy ◽

Andrea Tedeschi

Keyword(s):

Nervous System ◽

Lipid Metabolism ◽

Lipid Accumulation ◽

Axon Regeneration ◽

Axon Growth ◽

The Body ◽

Cns Repair ◽

Cord Injury ◽

Cns Trauma

Axons in the adult mammalian nervous system can extend over formidable distances, up to one meter or more in humans. During development, axonal and dendritic growth requires continuous addition of new membrane. Of the three major kinds of membrane lipids, phospholipids are the most abundant in all cell membranes, including neurons. Not only immature axons, but also severed axons in the adult require large amounts of lipids for axon regeneration to occur. Lipids also serve as energy storage, signaling molecules and they contribute to tissue physiology, as demonstrated by a variety of metabolic disorders in which harmful amounts of lipids accumulate in various tissues through the body. Detrimental changes in lipid metabolism and excess accumulation of lipids contribute to a lack of axon regeneration, poor neurological outcome and complications after a variety of central nervous system (CNS) trauma including brain and spinal cord injury. Recent evidence indicates that rewiring lipid metabolism can be manipulated for therapeutic gain, as it favors conditions for axon regeneration and CNS repair. Here, we review the role of lipids, lipid metabolism and ectopic lipid accumulation in axon growth, regeneration and CNS repair. In addition, we outline molecular and pharmacological strategies to fine-tune lipid composition and energy metabolism in neurons and non-neuronal cells that can be exploited to improve neurological recovery after CNS trauma and disease.

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Transcriptome Changes in Pseudomonas putida KT2440 during Medium-Chain-Length Polyhydroxyalkanoate Synthesis Induced by Nitrogen Limitation

International Journal of Molecular Sciences ◽

10.3390/ijms22010152 ◽

2020 ◽

Vol 22 (1) ◽

pp. 152

Author(s):

Dorota Dabrowska ◽

Justyna Mozejko-Ciesielska ◽

Tomasz Pokój ◽

Slawomir Ciesielski

Keyword(s):

Chain Length ◽

Nitrogen Limitation ◽

Stringent Response ◽

Wild Type ◽

Pseudomonas Putida Kt2440 ◽

Medium Chain ◽

Environmental Stimuli ◽

Medium Chain Length ◽

In The Wild

Pseudomonas putida’s versatility and metabolic flexibility make it an ideal biotechnological platform for producing valuable chemicals, such as medium-chain-length polyhydroxyalkanoates (mcl-PHAs), which are considered the next generation bioplastics. This bacterium responds to environmental stimuli by rearranging its metabolism to improve its fitness and increase its chances of survival in harsh environments. Mcl-PHAs play an important role in central metabolism, serving as a reservoir of carbon and energy. Due to the complexity of mcl-PHAs’ metabolism, the manner in which P. putida changes its transcriptome to favor mcl-PHA synthesis in response to environmental stimuli remains unclear. Therefore, our objective was to investigate how the P. putida KT2440 wild type and mutants adjust their transcriptomes to synthesize mcl-PHAs in response to nitrogen limitation when supplied with sodium gluconate as an external carbon source. We found that, under nitrogen limitation, mcl-PHA accumulation is significantly lower in the mutant deficient in the stringent response than in the wild type or the rpoN mutant. Transcriptome analysis revealed that, under N-limiting conditions, 24 genes were downregulated and 21 were upregulated that were common to all three strains. Additionally, potential regulators of these genes were identified: the global anaerobic regulator (Anr, consisting of FnrA, Fnrb, and FnrC), NorR, NasT, the sigma54-dependent transcriptional regulator, and the dual component NtrB/NtrC regulator all appear to play important roles in transcriptome rearrangement under N-limiting conditions. The role of these regulators in mcl-PHA synthesis is discussed.

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Oxygen control of nitrogen oxide respiration, focusing on α-proteobacteria

Biochemical Society Transactions ◽

10.1042/bst0390179 ◽

2011 ◽

Vol 39 (1) ◽

pp. 179-183 ◽

Cited By ~ 19

Author(s):

James P. Shapleigh

Keyword(s):

Nitrate Reductase ◽

Nitrogen Oxide ◽

Physiological Function ◽

Physiological Role ◽

Present Review ◽

Oxygen Control ◽

Anoxic Conditions ◽

Periplasmic Nitrate Reductase

Denitrification is generally considered to occur under micro-oxic or anoxic conditions. With this in mind, the physiological function and regulation of several steps in the denitrification of model α-proteobacteria are compared in the present review. Expression of the periplasmic nitrate reductase is quite variable, with this enzyme being maximally expressed under oxic conditions in some bacteria, but under micro-oxic conditions in others. Expression of nitrite and NO reductases in most denitrifiers is more tightly controlled, with expression only occurring under micro-oxic conditions. A possible exception to this may be Roseobacter denitrificans, but the physiological role of these enzymes under oxic conditions is uncertain.

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Lipid accumulation in multi-walled carbon nanotube-exposed HepG2 cells: Possible role of lipophagy pathway

Food and Chemical Toxicology ◽

10.1016/j.fct.2018.08.033 ◽

2018 ◽

Vol 121 ◽

pp. 65-71 ◽

Cited By ~ 7

Author(s):

Chunxue Zhao ◽

Yiwei Zhou ◽

Liangliang Liu ◽

Jimin Long ◽

Hongwen Liu ◽

...

Keyword(s):

Carbon Nanotube ◽

Lipid Accumulation ◽

Hepg2 Cells ◽

Multi Walled Carbon Nanotube

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Effects of BMP7 produced by group 2 innate lymphoid cells on adipogenesis

International Immunology ◽

10.1093/intimm/dxaa013 ◽

2020 ◽

Vol 32 (6) ◽

pp. 407-419 ◽

Cited By ~ 1

Author(s):

Yurina Miyajima ◽

Kafi N Ealey ◽

Yasutaka Motomura ◽

Miho Mochizuki ◽

Natsuki Takeno ◽

...

Keyword(s):

Lipid Accumulation ◽

Adipocyte Differentiation ◽

Allergic Inflammation ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Brown Adipocytes ◽

Morphogenetic Protein ◽

Group 2

Abstract Group 2 innate lymphoid cells (ILC2s) are type 2 cytokine-producing cells that have important roles in helminth infection and allergic inflammation. ILC2s are tissue-resident cells, and their phenotypes and roles are regulated by tissue-specific environmental factors. While the role of ILC2s in the lung, intestine and bone marrow has been elucidated in many studies, their role in adipose tissues is still unclear. Here, we report on the role of ILC2-derived bone morphogenetic protein 7 (BMP7) in adipocyte differentiation and lipid accumulation. Co-culture of fat-derived ILC2s with pluripotent mesenchymal C3H10T1/2 cells and committed white preadipocyte 3T3-L1 cells resulted in their differentiation to adipocytes and induced lipid accumulation. Co-culture experiments using BMP7-deficient ILC2s revealed that BMP7, produced by ILC2s, induces differentiation into brown adipocytes. Our results demonstrate that BMP7, produced by ILC2s, affects adipocyte differentiation, particularly in brown adipocytes.

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Role of ATP-binding cassette transporter A1 in suppressing lipid accumulation by glucagon-like peptide-1 agonist in hepatocytes

Molecular Metabolism ◽

10.1016/j.molmet.2019.12.015 ◽

2020 ◽

Vol 34 ◽

pp. 16-26

Author(s):

Jingya Lyu ◽

Hitomi Imachi ◽

Kensaku Fukunaga ◽

Seisuke Sato ◽

Toshihiro Kobayashi ◽

...

Keyword(s):

Lipid Accumulation ◽

Atp Binding ◽

Atp Binding Cassette Transporter ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Atp Binding Cassette

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Up-Regulated MicroRNA-27b Promotes Adipocyte Differentiation via Induction of Acyl-CoA Thioesterase 2 Expression

BioMed Research International ◽

10.1155/2019/2916243 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Yuka Murata ◽

Takashi Yamashiro ◽

Takaomi Kessoku ◽

Israt Jahan ◽

Haruki Usuda ◽

...

Keyword(s):

Liver Disease ◽

Lipid Accumulation ◽

Fatty Liver Disease ◽

Adipocyte Differentiation ◽

Aberrant Expression ◽

Nonalcoholic Fatty Liver ◽

Important Pathway ◽

The Impact ◽

Intracellular Triglyceride

Nonalcoholic fatty liver disease (NAFLD) is characterized by a spectrum of liver pathologies, from simple steatosis to steatohepatitis. Recent studies have increasingly noted the aberrant expression of microRNAs closely related to NAFLD pathologies. We have previously shown the presence of increased levels of microRNA-27b (miR-27b) in patients with NAFLD. In this study, we investigated the role of miR-27b in NAFLD by examining the impact of up-regulated miR-27b on the differentiation of preadipocytes into mature adipocytes. We found that miR-27b-3p remarkably enhances the adipocyte differentiation of 3T3-L1 cells associated with lipid accumulation and intracellular triglyceride contents. Furthermore, we have demonstrated not only that miR-27b-3p induces acyl-CoA thioesterase 2 (ACOT2) expression in 3T3-L1 cells, but also that the knockdown of ACOT2 suppresses lipid accumulation and adipocyte differentiation in both the presence and absence of miR-27b-3p treatment. Our data strongly suggest that the miR-27b-ACOT2 axis is an important pathway in adipocyte differentiation and may play a role in the pathogenesis of NAFLD.

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