MTCH2 is a conserved regulator of lipid homeostasis

Rottiers, Veerle; Francisco, Adam B.; Platov, Michael; Zaltsman, Yehudit; Ruggiero, Antonella; Lee, Siu Sylvia; Gross, Atan; Libert, Sergiy

doi:10.1002/oby.21751

Cited by 22 publications

(33 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2H) for further analysis as a candidate m 6 A gene in the regulation of intramuscular adipogenesis. Recent studies implicated MTCH2 in lipid accumulation and oxidation in mouse muscles (37) and Caenorhabditis elegans (38). In our study, we found that this gene exhibits relatively higher protein expression compared with L-LDM (P , 0.01) (Fig.…”

Section: Biologic Pathways Associated With M 6 A-modified Genessupporting

confidence: 65%

“…Recent studies have reported that MTCH2 regulates lipid accumulation in mouse muscle and that its deficiency leads to an increase in whole-body energy utilization and protection against diet-induced obesity (37). In addition, MTCH2 overexpression enhanced lipid accumulation in C. elegans by inhibiting the transcriptional activation of estrogen receptor 1 (38). In the present study, we found that MTCH2 mRNA and protein levels were higher in Jinhua pigs compared with those in Landrace pigs, and that MTCH2 protein was positively associated with adipogenesis in porcine intramuscular preadipocytes in the first 2 d after MDI induction.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m ⁶ A‐YTHDF1‐dependent mechanism

et al. 2018

View full text Add to dashboard Cite

Intramuscular fat is considered a potential factor that is associated with meat quality in animal production and insulin resistance in humans. N6‐methyladenosine (m6A) modification of mRNA plays an important role in regulating adipogenesis. However, the effects of m6A on the adipogenesis of intramuscular preadipocytes and associated mechanisms remain unknown. Here, we performed m6A sequencing to compare m6A methylome of the longissimus dorsi muscles (LDMs) between Landrace pigs (lean‐type breed) and Jinhua pigs (obese‐type breed with higher levels of intramuscular fat). Transcriptome‐wide m6A profiling of porcine LDMs was highly conserved with humans and mice. Furthermore, we identified a unique methylated gene in Jinhua pigs named mitochondrial carrier homology 2 (MTCH2). The m6A levels oiMTCHl mRNA were reduced by introducing a synonymous mutation, and adipogenesis test results showed that the MTCH2 mutant was inferior with regard to adipogenesis compared with the MTCH2 wild‐type. We then found that MTCH2 protein expression was positively associated with m6A levels, and an YTH domain family protein 1‐RNA immunoprecipitation‐quantitative PCR assay indicated that MTCH2 mRNA was a target of the YTH domain family protein 1. This study provides comprehensive m6A profiles of LDM transcriptomes in pigs and suggests an essential role for m6A modification of MTCH2 in intramuscular fat regulation.—Jiang, Q., Sun, B., Liu, Q., Cai, M., Wu, R., Wang, F., Yao, Y., Wang, Y., Wang, X. MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m6A‐YTHDF1‐dependent mechanism. FASEB J. 33, 2971–2981 (2019). http://www.fasebj.org

show abstract

Section: Biologic Pathways Associated With M 6 A-modified Genessupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m ⁶ A‐YTHDF1‐dependent mechanism

et al. 2018

View full text Add to dashboard Cite

show abstract

“…MTCH2 is a conserved regulator of lipid homeostasis. Knockdown of MTCH2/mtch2 reduced lipid accumulation (in adipocyte-like cells, C. elegans and mice) [ 15 ] and number of adipocytes (in zebrafish) [ 16 ], while overexpression of MTCH2 increased fat accumulation (in adipocyte-like cells, C. elegans and mice) [ 15 , 17 ]. Loss of muscle MTCH2 protected mice from diet-induced obesity and hyperinsulinemia and increased energy expenditure [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Computational analyses of obesity associated loci generated by genome-wide association studies

et al. 2018

View full text Add to dashboard Cite

ObjectivesGenome-wide association studies (GWASs) have discovered associations of numerous SNPs and genes with obesity. However, the underlying molecular mechanisms through which these SNPs and genes affect the predisposition to obesity remain not fully understood. Aims of our study are to comprehensively characterize obesity GWAS SNPs and genes through computational approaches.MethodsFor obesity GWAS identified SNPs, functional annotation, effects on miRNAs binding and impact on protein phosphorylation were performed via RegulomeDB and 3DSNP, miRNASNP, and the PhosSNP 1.0 database, respectively. For obesity associated genes, protein-protein interaction network construction, gene ontology and pathway enrichment analyses were performed by STRING, PANTHER and STRING, respectively.ResultsA total of 445 SNPs are significantly associated with obesity related phenotypes at threshold P < 5×10−8. A number of SNPs were eQTLs for obesity associated genes, some SNPs located at binding sites of obesity related transcription factors. SNPs that might affect miRNAs binding and protein phosphorylation were identified. Protein-protein interaction network analysis identified the highly-interconnected “hub” genes. Obesity associated genes mainly involved in metabolic process and catalytic activity, and significantly enriched in 15 signal pathways.ConclusionsOur results provided the targets for follow-up experimental testing and further shed new light on obesity pathophysiology.

show abstract

“…The biological role of MTCH2 in the brain is unclear. MTCH2 is known to contribute to adipocyte function, regulation of lipid metabolism [40,42], and to be genetically associated with obesity [43]. However, MTCH2 clearly has a role outside of adipocytes, as inhibition of MTCH2 increases products of metabolism, such as pyruvate and pyruvate dehydrogenase [44] in both brain and muscle.…”

Section: Mtch2 Chr11mentioning

confidence: 99%

“…It is not tremendously unexpected that MTCH2 has a direct impact on neurological function as the brain is one of the most metabolically active organs in the body. MTCH2 knockout mice exhibited deficits in both metabolic processes and hippocampal dependent spatial learning tasks [42,45,46]. There are known links between nutrition, specifically cholesterol consumption levels, in AD [47], which can also present health risks for cardiovascular function, another wellknown risk factor for AD.…”

Section: Mtch2 Chr11mentioning

confidence: 99%

Multi-Tissue Neocortical Transcriptome-Wide Association Study Implicates 8 Genes Across 6 Genomic Loci in Alzheimer’s Disease

Gockley

Montgomery

Poehlman

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractBackgroundAlzheimer’s disease (AD), an incurable neurodegenerative disease, currently affecting 1.75% of the United States population, with projected growth to 3.46% by 2050. Identifying common genetic variants driving differences in transcript expression that confer AD-risk is necessary to elucidate AD mechanism and develop therapeutic interventions. We modify the FUSION Transcriptome Wide Association Study (TWAS) pipeline to ingest expression from multiple neocortical regions, provide a set of 6780 gene weights which are abstracatable across the neocortex, and leverage these to find 8 genes from six loci with associated AD risk validated through summary mendelian randomization (SMR) utilizing IGAP summary statistics.MethodA combined dataset of 2003 genotypes clustered to Central European (CEU) ancestry was used to construct a training set of 790 genotypes paired to 888 RNASeq profiles across 6 Neo-cortical tissues (TCX=248, FP=50, IFG=41, STG=34, PHG=34, DLPFC=461). Following within-tissue normalization and covariate adjustment, predictive weights to impute expression components based on a gene’s surrounding cis-variants were trained. The FUSION pipeline was modified to support input of pre-scaled expression values and provide support for cross validation with a repeated measure design arising from the presence of multiple transcriptome samples from the same individual across different tissues.ResultsCis-variant architecture alone was informative to train weights and impute expression for 6780 (49.67%) autosomal genes, the majority of which significantly correlated with gene expression; FDR < 5%: N=6775 (99.92%), Bonferroni: N=6716 (99.06%). Validation of weights in 515 matched genotype to RNASeq profiles from the CommonMind Consortium (CMC) was (72.14%) in DLPFC profiles. Association of imputed expression components from all 2003 genotype profiles yielded 8 genes significantly associated with AD (FDR < 0.05); APOC1, EED, CD2AP, CEACAM19, CLPTM1, MTCH2, TREM2, KNOP1.ConclusionWe provide evidence of cis-genetic variation conferring AD risk through 8 genes across six distinct genomic loci. Moreover, we provide expression weights for 6780 genes as a valuable resource to the community, which can be abstracted across the neocortex and a wide range of neuronal phenotypes.

show abstract

MTCH2 is a conserved regulator of lipid homeostasis

Cited by 22 publications

References 42 publications

MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m ⁶ A‐YTHDF1‐dependent mechanism

MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m ⁶ A‐YTHDF1‐dependent mechanism

Computational analyses of obesity associated loci generated by genome-wide association studies

Multi-Tissue Neocortical Transcriptome-Wide Association Study Implicates 8 Genes Across 6 Genomic Loci in Alzheimer’s Disease

Contact Info

Product

Resources

About

MTCH2 is a conserved regulator of lipid homeostasis

Cited by 22 publications

References 42 publications

MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m 6 A‐YTHDF1‐dependent mechanism

MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m 6 A‐YTHDF1‐dependent mechanism

Computational analyses of obesity associated loci generated by genome-wide association studies

Multi-Tissue Neocortical Transcriptome-Wide Association Study Implicates 8 Genes Across 6 Genomic Loci in Alzheimer’s Disease

Contact Info

Product

Resources

About

MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m ⁶ A‐YTHDF1‐dependent mechanism

MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m ⁶ A‐YTHDF1‐dependent mechanism