Active brown fat engages fatty acid synthesis through AKT2 stimulated ChREBP activity, simultaneously with fatty acid oxidation, to maintain fuel storage
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA379360 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5349230.fastq.gz | Fastqsanger.gz | |||
| SRR5349240.fastq.gz | Fastqsanger.gz | |||
| SRR5349250.fastq.gz | Fastqsanger.gz | |||
| SRR5349260.fastq.gz | Fastqsanger.gz | |||
| SRR5349270.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Intramuscular fat (IMF) content is one of the key factors affecting meat quality. Carbohydrate response element binding protein (ChREBP) can promote glucose metabolism and fat synthesis by activating the expression of glycolysis and lipogenesis-related genes, but its function and regulatory mechanism in IMF are still unclear. This study evaluated the correlation between TG content and ChREBP expression level in muscles of different species to reveal the relationship between ChREBP and IMF. RNA-seq analysis showed that overexpressing ChREBP in C2C12 cells can significantly up-regulate fatty acid synthesis pathways, while significantly down-regulate the expression levels of muscle development pathways and related genes. In vivo, we found that overexpression of ChREBP or activation by fructose significantly increased the triglyceride content of the tibialis anterior muscle (TA) and the IMF content of yellow feather chicken leg and breast muscle in mice. And lipidomics data also found that feeding fructose can change the lipid composition of yellow feather broiler breast muscle and improve the flavor substances. This study demonstrated that ChREBP is a key gene regulating IMF deposition, providing a new target for genetic selection and nutritional regulation of IMF content.
2024-08-08 | GSE228899 | GEO
Project description:By analogy to the c-Myc (Myc)/Max family of transcription factors, there also exists a “parallel” network of structurally and functionally related bHLH-ZIP proteins with certain Myc-like functions. Two closely related “Myc-like” paralogs termed Mondo A and MondoB/ChREBP (ChREBP) positively regulate gene expression in heterodimeric association with the Max-like factor Mlx. Myc is necessary to support liver cancer cell growth but not for normal hepatocyte proliferation. Here, we investigated the role for ChREBP and its relationship to Myc in these processes. Unlike Myc, ChREBP loss conferred a marked proliferative disadvantage to normal hepatocytes as did the loss of both ChREBP and Myc. In addition, hepatoblastomas (HBs) originating in myc-/-, chrebp-/- or myc-/-/chrebp-/- backgrounds grew significantly more slowly. Metabolic studies performed on livers and HBs arising in all three backgrounds showed marked differences in oxidative phosphorylation, fatty acid -oxidation (FAO) and the activity of pyruvate dehydrogenase. RNAseq of livers and HBs indicated seven distinct forms of target transcript regulation. Gene ontology analysis indicated that many transcripts de-regulated in the chrebp-/- background encode enzymes functioning in glycolysis, the TCA cycle and - and-FAO whereas those in myc-/- background encode enzymes for glycolysis, glutaminolysis and sterol biosynthesis. Transcript de-regulation in the double knockout group was similar but also included those involved in peroxisomal - and -FAO. Finally, we identified cooperative positive regulation by Myc and ChREBP of virtually all ribosomal protein genes. Our findings define the global proliferative, metabolic and transcriptional roles for the more general “Extended Myc Network” under both normal and neoplastic conditions.
2018-08-09 | GSE114634 | GEO
Project description:Biallelic inactivating mutations of the transcription factor 1 gene (TCF1), encoding hepatocyte nuclear factor 1a (HNF1a), were identified in 50% of hepatocellular adenomas (HCA) phenotypically characterized by a striking steatosis. To understand the molecular basis of this aberrant lipid storage, we performed a microarray transcriptome analysis validated by quantitative RT-PCR, western-blotting and lipid profiling. In mutated HCA, we showed a repression of gluconeogenesis coordinated with an activation of glycolysis, citrate shuttle and fatty acid synthesis predicting elevated rates of lipogenesis. Moreover, the strong dowregulation of L-FABP suggests that impaired fatty acid trafficking may also contribute to the fatty phenotype. In addition, transcriptional profile analysis of the observed deregulated genes in non-HNF1a-mutated HCA as well as in non-tumor livers allowed us to define a specific signature of the HNF1a-mutated HCA. In theses tumors, lipid composition was dramatically modified according to the transcriptional deregulations identified in the fatty acid synthetic pathway. Surprisingly, lipogenesis activation did not operate through SREBP-1 and ChREBP that were repressed. We conclude that steatosis in HNF1a-mutated HCA results mainly from an aberrant promotion of lipogenesis that is linked to HNF1a inactivation and that is independent of both SREBP-1 and ChREBP activation. Finally, our findings have potential clinical implications since lipogenesis can be efficiently inhibited by targeted therapies. Keywords: Disease state analysis
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Project description:This project investigated proline hydroxylation of ChREBP. Proline hydroxylation was investigated in flag-IP enriched protein extracts from ChREBP-flag overexpressing HEK293 cells (A) and in ChREBP-IP enriched mouse liver protein (male, C57BL6/J) (B).
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Project description:Epidemiologic and animal studies implicate overconsumption of fructose in the development of non-alcoholic fatty liver disease, but the molecular mechanisms underlying fructose-induced chronic liver diseases remains largely unknown. We present evidence supporting the essential function of the lipogenic transcription factor ChREBP in mediating adaptation response to fructose and protecting against fructose-induced hepatotoxicity. High-fructose diet (HFrD) activates hepatic lipogenesis via a ChREBP-dependent manner in wildtype mice, while inducing steatohepatitis in Chrebp-KO mice. In Chrebp-KO mouse livers, HFrD reduces levels of molecular chaperones and activates the CHOP-dependent unfolded protein response, whereas administration of chemical chaperone or Chop shRNA rescues liver injury. Gene expression profiling revealed elevated expression of cholesterol biosynthesis genes in Chrebp-KO livers after HFrD, in parallel with increased abundance of nuclear SREBP2. genes expression were compared between livers of wildtype mice fed 70%-fructose-diet v.s. regular chow, and between livers of Chrebp-/- mice v.s. wildtype mice fed 70%-fructose-diet.
2017-03-21 | GSE96820 | GEO
Project description:The relevance of adipose-derived long noncoding RNAs (lncRNAs) to the regulation of gene expression patterns related to the obese phenotype remains elusive. Here, the analysis of transcriptomes of adipose tissue before-after significant weight loss led to the identification of 496 putative lncRNAs (FDR p-values <0.05). Only the nonconserved linc-GALNTL6-4 displayed a fold-change above 2 plus adjusted p-value <0.0001. Exploration of additional omental and subcutaneous fat samples confirmed diminished linc-GALNTL6-4 in obese subjects, while lncRNA-mRNA co-expression analyses highlighted its association with fatty acid metabolism. Concurrently, the expression of this unique lncRNA towered in ex vivo isolated and in vitro differentiated adipocytes, being compromised under conditions that mimicked inflammation in obese adipocytes. On the other hand, the knockdown of linc-GALNTL6-4 in fat cell progenitors conveys impaired differentiation, fostering deranged expression patterns in differentiated adipocytes, including the increased expression of genes devoted to the transport of lipids, such as Apolipoprotein C1 (APOC1) and the intracellular fatty acid-binding protein FABP3. Conversely, overexpression of linc-GALNTL6-4 ameliorated adipocyte performance through the specific control of the short-chain fatty acid receptor FFAR3. Current data unveil the unforeseen relevance of linc-GALNTL6-4 as a modulator of fatty acid sensing in adipocytes deeply challenged by body weight and meta-inflammation.
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Project description:The relevance of adipose-derived long noncoding RNAs (lncRNAs) to the regulation of gene expression patterns related to the obese phenotype remains elusive. Here, the analysis of transcriptomes of adipose tissue before-after significant weight loss led to the identification of 496 putative lncRNAs (FDR p-values <0.05). Only the nonconserved linc-GALNTL6-4 displayed a fold-change above 2 plus adjusted p-value <0.0001. Exploration of additional omental and subcutaneous fat samples confirmed diminished linc-GALNTL6-4 in obese subjects, while lncRNA-mRNA co-expression analyses highlighted its association with fatty acid metabolism. Concurrently, the expression of this unique lncRNA towered in ex vivo isolated and in vitro differentiated adipocytes, being compromised under conditions that mimicked inflammation in obese adipocytes. On the other hand, the knockdown of linc-GALNTL6-4 in fat cell progenitors conveys impaired differentiation, fostering deranged expression patterns in differentiated adipocytes, including the increased expression of genes devoted to the transport of lipids, such as Apolipoprotein C1 (APOC1) and the intracellular fatty acid-binding protein FABP3. Conversely, overexpression of linc-GALNTL6-4 ameliorated adipocyte performance through the specific control of the short-chain fatty acid receptor FFAR3. Current data unveil the unforeseen relevance of linc-GALNTL6-4 as a modulator of fatty acid sensing in adipocytes deeply challenged by body weight and meta-inflammation.
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