Sex Differences in BAT Thermogenesis in PGC1α Knockout Mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1219295 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32233440_1.fastq.gz | Fastqsanger.gz | |||
| SRR32233440_2.fastq.gz | Fastqsanger.gz | |||
| SRR32233441_1.fastq.gz | Fastqsanger.gz | |||
| SRR32233441_2.fastq.gz | Fastqsanger.gz | |||
| SRR32233442_1.fastq.gz | Fastqsanger.gz |
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Project description:To elucidate the sex-specific role of PGC1α in brown adipose tissue (BAT), we performed RNA-seq analysis on BAT from male and female PGC1α knockout mice. Furthermore, to investigate the effects of estrogen on BAT, we conducted RNA-seq analysis on BAT from male and female wild-type mice treated with tamoxifen.
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Project description:The increasing incidence of obesity poses great challenges and demands for developing effective therapeutic approaches. We aimed to reveal the anti-obesity effects of tetrahydroberberrubine (THBru), a derivative of berberine (BBR) and elucidate its underlying mechanism. The anti-obesity effects of THBru and BBR were assessed and compared using an obese mouse model induced by high fat diet (HFD). THBru was found to markedly ameliorated obesity, indicated by reduced body weight, decreased Lee’s index, lowered epididymal white adipose tissue (WAT) and brown adipose tissue (BAT) fat mass as well as improved dyslipidemia. At the same dose, THBru produced greater anti-obesity effects than BBR. RNA-sequencing and gene set enrichment analysis indicated THBru activated thermogenesis, which was further confirmed in WAT, BAT, and 3T3-L1 cells. Bioinformatics analysis of RNA-sequencing data revealed the candidate gene Pgc1α, a key regulator involved in thermogenesis. Moreover, THBru was demonstrated to elevate the expression of PGC1α by stabilizing its mRNA in WAT, BAT and 3T3-L1 cells. Furthermore, PGC1α knockdown blocked the pro-thermogenic and anti-obesity action of THBru both in vivo and in vitro. This study indicated THBru exerted anti-obesity effects by activating PGC1α-mediated thermogenesis and outlined its potential preventive and therapeutic implications for obesity and related diseases.
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Project description:We reported that both conventional and adipose-specific Naa10p deletions in mice result in increased energy expenditure, thermogenesis, beige adipocyte differentiation and activation. Mechanistically, Naa10p acetylates the N-terminus of Pgc1α and prevents it from interacting with Ppar to activate key genes, such as Ucp1, involved in beige adipocyte function. We used microarrays to profile the gene expression changes by Naa10p KO in inguinal white adipose tissues (iWATs) derived from mice fed with high fat diet for 15 weeks.
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Project description:Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Epigenetic regulation has emerged as a key mechanism underlying BAT development and function. To study the epigenetic regulation of BAT thermogenesis, we surveyed the expression of epigenetic enzymes that catalyze histone modifications in developmental beige adipocytes and found a unique expression pattern of suppressor of variegation 4-20 homolog 2 (Drosophila) (Suv420h2), a histone methyltransferase that preferentially catalyzes the tri-methylation at histone H4 lysine 20 (H4K20me3), a hallmark of gene silencing. Here we discovered that Suv420h2 expression parallels that of UCP1 expression in brown and beige adipocytes and that SUV420H2 knockdown significantly reduces, whereas SUV420H2 overexpression significantly increases UCP1 levels in brown adipocytes. Suv420h2 knockout (H2KO mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study showed that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) promoter, leading to down-regulated expression of 4E-BP1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.
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