Satellite glial cells promote regenerative growth in sensory neurons

Abstract Peripheral sensory neurons regenerate their axon after nerve injury to enable functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, contribute to nerve regeneration remains unexplored. Using a single cell RNAseq approach, we reveal that SGC are distinct from Schwann cells and share similarities with astrocytes. Nerve injury elicits changes in the expression of genes related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARα) signaling. Conditional deletion of fatty acid synthase (Fasn) in SGC impairs axon regeneration. The PPARα agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC. These results indicate that PPARα activity downstream of FASN in SGC contributes to promote axon regeneration in adult peripheral nerves and highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair.

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Satellite glial cells promote regenerative growth in sensory neurons

10.1101/2019.12.13.874669 ◽

2019 ◽

Author(s):

Oshri Avraham ◽

Pan-Yue Deng ◽

Sara Jones ◽

Rejji Kuruvilla ◽

Clay F. Semenkovich ◽

...

Keyword(s):

Fatty Acid ◽

Nerve Injury ◽

Sensory Neurons ◽

Glial Cells ◽

Fatty Acid Synthesis ◽

Fatty Acid Synthase ◽

Axon Regeneration ◽

Nerve Repair ◽

Acid Synthesis ◽

Satellite Glial Cells

SUMMARYPeripheral sensory neurons switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, undergo injury-evoked transcriptional changes and contribute to nerve regeneration remains unexplored. This is largely due to the lack of molecular and genetic tools to study SGC. Using a single cell RNAseq approach to define the transcriptional profile of SGC in naïve and injured conditions, we reveal that these cells are distinct from Schwann cells and share similarities with astrocytes. We find that nerve injury elicits gene expression changes in SGC, which are related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARα) signaling. Conditional deletion of Fatty acid synthase (Fasn), the committed enzyme in de novo fatty acid synthesis, in SGC, impairs axon regeneration. The PPARα agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC, indicating that PPARα functions downstream of fatty acid synthesis in SGC to promote axon regeneration. These results identify fatty acid synthesis in SGC as a fundamental novel mechanism mediating axon regeneration in adult peripheral nerves. These results also highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair.

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Polyunsaturated Fatty Acid Suppression of Hepatic Fatty Acid Synthase and S14 Gene Expression Does Not Require Peroxisome Proliferator-activated Receptor α

Journal of Biological Chemistry ◽

10.1074/jbc.272.43.26827 ◽

1997 ◽

Vol 272 (43) ◽

pp. 26827-26832 ◽

Cited By ~ 199

Author(s):

Bing Ren ◽

Annette P. Thelen ◽

Jeffrey M. Peters ◽

Frank J. Gonzalez ◽

Donald B. Jump

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Polyunsaturated Fatty Acid ◽

Fatty Acid Synthase ◽

Acid Suppression ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Hepatic Fatty Acid

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Genistin: A Novel Potent Anti-Adipogenic and Anti-Lipogenic Agent

Molecules ◽

10.3390/molecules25092042 ◽

2020 ◽

Vol 25 (9) ◽

pp. 2042 ◽

Cited By ~ 1

Author(s):

Yae Rim Choi ◽

Jaewon Shim ◽

Min Jung Kim

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthase ◽

Binding Protein ◽

Regulatory Element ◽

Peroxisome Proliferator ◽

Dependent Manner ◽

Atp Citrate Lyase ◽

Peroxisome Proliferator Activated Receptor ◽

Fatty Acid Binding ◽

Specific Proteins

Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are well-known, but those of genistin and glycitein remain unknown, and those of daidzein are characterized by contrasting data. Therefore, the purpose of our study was to investigate the effects of daidzein, glycitein, genistein, and genistin on adipogenesis and lipogenesis in 3T3-L1 cells. Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein, but it was affected by 50 and 100 µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones, only 50 and 100 µM genistin and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner. Genistin and genistein suppress adipocyte-specific proteins and genes, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), and adipocyte binding protein 2 (aP2)/fatty acid-binding protein 4 (FABP4), and lipogenic enzymes such as ATP citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS). Both isoflavones also activate AMP-activated protein kinase α (AMPKα), an essential factor in adipocyte differentiation, and inhibited sterol regulatory element-binding transcription factor 1c (SREBP-1c). These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent.

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Gene expressions of de novo hepatic lipogenesis in feline hepatic lipidosis

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x19857853 ◽

2019 ◽

Vol 22 (6) ◽

pp. 500-505

Author(s):

Chiara Valtolina ◽

Joris H Robben ◽

Monique E van Wolferen ◽

Hedwig S Kruitwagen ◽

Ronald J Corbee ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Liver Tissue ◽

Fatty Acid Synthase ◽

De Novo ◽

Control Group ◽

Peroxisome Proliferator ◽

Hepatic Lipidosis ◽

Peroxisome Proliferator Activated Receptor ◽

Ppar Γ

Objectives The aim of this study was to evaluate if de novo hepatic lipid synthesis contributes to fatty acid overload in the liver of cats with feline hepatic lipidosis (FHL). Methods Lipogenic gene expression of peroxisome proliferator-activated receptor-alpha ( PPAR-α), peroxisome proliferator-activated receptor-gamma ( PPAR-γ), fatty acid synthase ( FASN) and sterol regulatory element-binding factor ( SREBF1) were evaluated using quantitative RT-PCR in liver tissue of six cats with FHL and compared with the liver tissue of eight healthy cats. Results In liver tissue, PPAR-α, PPAR-γ and FASN mRNA expression levels were not significantly different ( P >0.12, P >0.89 and P >0.5, respectively) in the FHL group compared with the control group. SREBF1 gene expression was downregulated around 10-fold in the FHL group vs the control group ( P = 0.039). Conclusions and relevance The downregulation of SREBF1 in the liver tissue of cats with FHL does not support the hypothesis that de novo lipogenesis in the liver is an important pathway of fatty acid accumulation in FHL.

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Flavonones from Penthorum chinense Ameliorate Hepatic Steatosis by Activating the SIRT1/AMPK Pathway in HepG2 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19092555 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2555 ◽

Cited By ~ 10

Author(s):

Wei-Wei Guo ◽

Xing Wang ◽

Xiao-Qing Chen ◽

Yin-Ying Ba ◽

Nan Zhang ◽

...

Keyword(s):

Fatty Acid ◽

Hepatic Steatosis ◽

Hepg2 Cells ◽

Fatty Acid Synthase ◽

Molecular Mechanisms ◽

Regulatory Element ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Ampk Pathway ◽

Penthorum Chinense

Pinocembrin-7-O-β-d-glucoside (PCBG), pinocembrin (PCB), and 5-methoxy-pinocembrin-7-O-β-d-glucoside (MPG) are three flavonones isolated from Penthorum chinense Pursh (P. chinense). The effects of the three flavonones on hepatic steatosis and their molecular mechanisms in HepG2 cells were investigated in this study for the first time. A model of hepatic steatosis in HepG2 cells was induced by free fatty acid (FFA), and co-treated with the three flavonones as mentioned. Intracellular lipid droplets were detected by Oil Red O staining. PCB, PCBG, and MPG suppressed oxidative stress by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were ameliorated. Moreover, these flavonones enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of silent mating type information regulation 2 homolog 1 (SIRT1) and peroxisome proliferator-activated receptor α (PPARα), and reduced the expression of sterol regulatory element binding protein-1c (SREBP1c) and the downstream targets fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl-CoA desaturase 1 (SCD1). Molecular docking was used to predict the interaction and combination patterns between the three flavonones and the enzymes above. The results revealed that the SIRT1/AMPK pathway is involved in the functions of the three flavonones, and the most effective flavonone against hepatic steatosis might be PCBG, followed by MPG and PCB. Therefore, the three flavonones from P. chinense were found to exert preventive effects against hepatic steatosis by regulating the SIRT1/AMPK pathway.

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Induction of a reactive state in perineuronal satellite glial cells akin to that produced by nerve injury is linked to the level of p75NTR expression in adult sensory neurons

Glia ◽

10.1002/glia.22640 ◽

2014 ◽

Vol 62 (5) ◽

pp. 763-777 ◽

Cited By ~ 11

Author(s):

Joelle R. Nadeau ◽

Tracy D. Wilson-Gerwing ◽

Valerie M.K. Verge

Keyword(s):

Nerve Injury ◽

Sensory Neurons ◽

Glial Cells ◽

Satellite Glial Cells

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Differential expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, and hormone-sensitive lipase in fat-tailed and thin-tailed sheep breeds

Genetics and Molecular Research ◽

10.4238/2015.december.1.14 ◽

2015 ◽

Vol 14 (4) ◽

pp. 15624-15633 ◽

Cited By ~ 6

Author(s):

X.C. Xu ◽

B.B. Li ◽

X. Wei ◽

Y.X. Yang ◽

X.L. Wang ◽

...

Keyword(s):

Fatty Acid ◽

Differential Expression ◽

Fatty Acid Synthase ◽

Hormone Sensitive Lipase ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Sheep Breeds ◽

Hormone Sensitive

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De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination

The Journal of Cell Biology ◽

10.1083/jcb.201706010 ◽

2018 ◽

Vol 217 (4) ◽

pp. 1353-1368 ◽

Cited By ~ 23

Author(s):

Laura Montani ◽

Jorge A. Pereira ◽

Camilla Norrmén ◽

Hartmut B.F. Pohl ◽

Elisa Tinelli ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthase ◽

De Novo ◽

Ex Vivo ◽

Intrinsic Activity ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Endogenous Fatty Acid ◽

Pparγ Agonist

Myelination calls for a remarkable surge in cell metabolism to facilitate lipid and membrane production. Endogenous fatty acid (FA) synthesis represents a potentially critical process in myelinating glia. Using genetically modified mice, we show that Schwann cell (SC) intrinsic activity of the enzyme essential for de novo FA synthesis, fatty acid synthase (FASN), is crucial for precise lipid composition of peripheral nerves and fundamental for the correct onset of myelination and proper myelin growth. Upon FASN depletion in SCs, epineurial adipocytes undergo lipolysis, suggestive of a compensatory role. Mechanistically, we found that a lack of FASN in SCs leads to an impairment of the peroxisome proliferator-activated receptor (PPAR) γ–regulated transcriptional program. In agreement, defects in myelination of FASN-deficient SCs could be ameliorated by treatment with the PPARγ agonist rosiglitazone ex vivo and in vivo. Our results reveal that FASN-driven de novo FA synthesis in SCs is mandatory for myelination and identify lipogenic activation of the PPARγ transcriptional network as a putative downstream functional mediator.

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Nano-Zn Increased Zn Accumulation and Triglyceride Content by Up-Regulating Lipogenesis in Freshwater Teleost, Yellow Catfish Pelteobagrus fulvidraco

International Journal of Molecular Sciences ◽

10.3390/ijms21051615 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1615 ◽

Cited By ~ 1

Author(s):

Shi-Cheng Ling ◽

Mei-Qin Zhuo ◽

Dian-Guang Zhang ◽

Heng-Yang Cui ◽

Zhi Luo

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthase ◽

Pelteobagrus Fulvidraco ◽

Fatty Acid Transport ◽

Peroxisome Proliferator ◽

Mrna Levels ◽

Yellow Catfish ◽

Peroxisome Proliferator Activated Receptor ◽

Lipogenic Genes ◽

Zn Accumulation

The present study was conducted to explore the mechanism of nano-Zn absorption and its influence on lipid metabolism in the intestine of yellow catfish Pelteobagrus fulvidraco. Compared to ZnSO4, dietary nano-Zn addition increased the triglyceride (TG) content, enzymatic activities of malic enzyme (ME) and fatty acid synthase (FAS), and up-regulated mRNA levels of 6pgd, fas, acca, dgat1, pparγ, and fatp4. Using primary intestinal epithelial cells of yellow catfish, compared to the ZnSO4 group, nano-Zn incubation increased the contents of TG and free fatty acids (FFA), the activities of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6GPD), ME, and FAS, up-regulated mRNA levels of lipogenic genes (6pgd, g6pd, fas, dgat1, and pparγ), genes of lipid transport (fatp4 and ifabp), and Zn transport genes (znt5, znt7, mt, and mtf1), and increased the protein expression of fatty acid transport protein 4 (FATP4) and peroxisome proliferator activated receptor gamma (PPARγ). Further studies found that nano-Zn absorption was via the clathrin-dependent endocytic mechanism. PPARγ mediated the nano-Zn-induced increase in TG, and nano-Zn increased Zn accumulation and induced TG accumulation by activating the PPARγ pathway and up-regulating lipogenesis.

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