Lipid Metabolism and Axon Degeneration: An ACOX1 Balancing Act

Griffin, Emily N.; Ackerman, Susan L.

doi:10.1016/j.neuron.2020.04.030

Cited by 12 publications

(6 citation statements)

References 10 publications

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“…Next, the NRG3 gene has been found to be related to cognitive deficit in schizophrenia [65], as well as bipolar disorder and major depressive disorder [78]. Finally, mutations in the ACOX1 gene are associated with neurodegeneration [42]. All three genes play important roles in biological processes, and impact psychiatric and general health in a variety of ways.…”

Section: Resultsmentioning

confidence: 99%

Differentially methylated regions and methylation QTLs for teen depression and early puberty in the Fragile Families Child Wellbeing Study

Aguiar

et al. 2021

Preprint

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The Fragile Families Child Wellbeing Study (FFCWS) is a longitudinal cohort of ethnically diverse and primarily low socioeconomic status children and their families in the U.S. Here, we analyze DNA methylation data collected from 748 FFCWS participants in two waves of this study, corresponding to participant ages 9 and 15. Our primary goal is to leverage the DNA methylation data from these two time points to study methylation associated with two key traits in adolescent health that are over-represented in these data: Early puberty and teen depression. We first identify differentially methylated regions (DMRs) for depression and early puberty. We then identify DMRs for the interaction effects between these two conditions and age by including interaction terms in our regression models to understand how age-related changes in methylation are influenced by depression or early puberty. Next, we identify methylation quantitative trait loci (meQTLs) using genotype data from the participants. We also identify meQTLs with epistatic effects with depression and early puberty. We find enrichment of our interaction meQTLs with functional categories of the genome that contribute to the heritability of co-morbid complex diseases. We replicate our meQTLs in data from the GoDMC study. This work leverages the important focus of the FFCWS data on disadvantaged children to shed light on the methylation states associated with teen depression and early puberty, and on how genetic regulation of methylation is affected in adolescents with these two conditions.

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Section: Resultsmentioning

confidence: 99%

Differentially methylated regions and methylation QTLs for teen depression and early puberty in the Fragile Families Child Wellbeing Study

Aguiar

et al. 2021

Preprint

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“… 24 ACOX1 is the first and rate-limiting enzyme required for peroxisomal β-oxidation of long-chain fatty acids. 25 ACADM has also been shown to regulate fatty acid oxidation. 26 As observed in the present study, canagliflozin upregulated the expression of CPT1a, ACOX1, and ACADM proteins in hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Canagliflozin Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism and Inhibiting Inflammation through Induction of Autophagy

Wang

et al. 2022

Yonsei Med J

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Purpose Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic diseases, including obesity and diabetes, and has gradually become the most common cause of chronic liver disease. We investigated the effects of sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin on NAFLD in high-fat diet (HFD)-induced obese mice and possible underlying mechanisms. Materials and Methods Male C57BL/6 mice were fed a normal-diet, HFD, or HFD with canagliflozin for 14 weeks. AML-12 hepatocytes were treated with canagliflozin. Expression of related pathways was assessed. Results Canagliflozin administration reduced body weight and fat mass, compared with HFD alone. Canagliflozin improved glucose and lipid metabolic disorders. Compared with HFD-fed mice, liver weight, serum alanine transaminase (ALT) levels, and hepatic lipid accumulation were decreased after canagliflozin administration. Additionally, canagliflozin upregulated lipolysis markers (CPT1a, ACOX1, and ACADM), downregulated lipogenesis markers (SREBP-1c and FASN), and suppressed the production of inflammatory cytokines (TNFα, MCP1, IL-1β, and IL-6), consistent with significantly increased LC3 II/I and Atg7 levels in the liver following canagliflozin treatment. In vitro, canagliflozin increased CPT1a, ACOX1, and ACADM expression, decreased SREBP-1c and FASN protein expression, and reduced TNFα, MCP1, IL-1β, and IL-6 mRNA levels in lipid mixture (LM)-induced hepatocytes in a dose-dependent manner. These changes were reversed by 3-MA, an autophagy inhibitor. Conclusion Our findings suggest that canagliflozin ameliorates the pathogenesis of NAFLD by regulating lipid metabolism and inhibiting inflammation, which may be associated with its promotion of autophagy.

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“…Notably, some downstream target genes in the ceRNA network have already been reported to be complicated in the nerve regeneration process. For instance, Acox1, a downstream target molecule of miR-6331-z, is required for axon regeneration and its mutation induces axonal loss and axon degeneration ( Chung et al, 2020 ; Griffin and Ackerman, 2020 ; Shimizu et al, 2022 ). Ecel1, a target of miR-129-x, displays robust transcriptional responses to nerve injury and is considered as a potential therapeutic target for nerve regeneration ( Kiryu-Seo et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Characterization of circular RNAs in dorsal root ganglia after central and peripheral axon injuries

Cao

Huang

Zheng

et al. 2022

Front. Cell. Neurosci.

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In central nervous system, axons fail to regenerate after injury while in peripheral nervous system, axons retain certain regenerative ability. Dorsal root ganglion (DRG) neuron has an ascending central axon branch and a descending peripheral axon branch stemming from one single axon and serves as a suitable model for the comparison of growth competence following central and peripheral axon injuries. Molecular alterations underpin different injury responses of DRG branches have been investigated from many aspects, such as coding gene expression, chromatin accessibility, and histone acetylation. However, changes of circular RNAs are poorly characterized. In the present study, we comprehensively investigate circular RNA expressions in DRGs after rat central and peripheral axon injuries using sequencing analysis and identify a total of 33 differentially expressed circular RNAs after central branch injury as well as 55 differentially expressed circular RNAs after peripheral branch injury. Functional enrichment of host genes of differentially expressed circular RNAs demonstrate the participation of Hippo signaling pathway and Notch signaling pathway after both central and peripheral axon injuries. Circular RNA changes after central axon injury are also linked with apoptosis and cellular junction while changes after peripheral axon injury are associated with metabolism and PTEN-related pathways. Altogether, the present study offers a systematic evaluation of alterations of circular RNAs in rat DRGs following injuries to the central and peripheral axon branches and contributes to the deciphering of essential biological activities and mechanisms behind successful nerve regeneration.

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Lipid Metabolism and Axon Degeneration: An ACOX1 Balancing Act

Cited by 12 publications

References 10 publications

Differentially methylated regions and methylation QTLs for teen depression and early puberty in the Fragile Families Child Wellbeing Study

Differentially methylated regions and methylation QTLs for teen depression and early puberty in the Fragile Families Child Wellbeing Study

Canagliflozin Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism and Inhibiting Inflammation through Induction of Autophagy

Characterization of circular RNAs in dorsal root ganglia after central and peripheral axon injuries

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