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RNAseq analysis of adipose tissue transcriptomes from wild-type and FNIP1 adipocyte specific knockout (FNIP1-AKO) mice

ABSTRACT: Activation of thermogenesis in brown and beige adipocytes upon activation by external stimuli burns fuel energy as heat. Owing to its remarkable benefits on metabolic health and its demonstrated presence in adult humans, beige adipocytes holds great promise to combat obesity and metabolic diseases. Folliculin interacting protein 1 (FNIP1) is an adaptor protein originally identified through its interaction with folliculin (FLCN) and AMPK. To investigate the physiological role of FNIP1 in adipose tissue in vivo, we generated adipocyte-specific FNIP1 deficient mice (referred to as FNIP1-AKO) by crossing mice bearing a conditional Fnip1 allele with introns 5 and 6 floxed (Fnip1 lox/lox) with the adiponectin promoter–driven Cre mice. We performed transcriptome analysis by whole-genome gene expression profiling experiments in inguinal white adipose tissue (iWAT) from both wild-type (WT) and FNIP1-AKO mice. We were particularly interested in the subset of genes that were up-regulated in the FNIP1-AKO mice. Gene ontology (GO) analysis revealed that the primary up-regulated genes were mitochondrial and lipid metabolism-related genes. Gene expression validation studies demonstrated that a broad array of genes involved in thermogenic and mitochondrial oxidative program was induced in FNIP1-AKO iWAT. Together, the transcriptional profiling results indicate that loss of FNIP1 activate thermogenic program in white adipocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE185067 | GEO | 2022/02/26

REPOSITORIES: GEO

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Genome-wide mapping of H3K4me1 status in primary adipocytes isolated from wild-type (WT) and Lonp1-knockout (LONP1 AKO) mice

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The Folliculin-Fnip1 pathway deleted in human Birt-Hogg-Dube syndrome is required for B cell development.

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RNAseq analysis of skeletal muscle transcriptomes from wild-type, FNIP1-knockout (FNIP1-KO) mice, and mice expressing FNIP1 only in skeletal muscle (FNIP1-TgKO).

Project description:This experiment was conducted to identify FNIP1-dependent mRNA transcripts alteration in skeletal muscle. Mouse FNIP1 was specifically overexpressed in skeletal muscle in FNIP1-transgenic (FNIP1-Tg) mice. FNIP1-Tg mice were crossed with FNIP1-knockout (FNIP1-KO) mice to generate FNIP1-TgKO mice expressing FNIP1 only in skeletal muscle but not in other tissues. The muscle glycolytic-to-oxidative transformation is determined, largely in part, at the level of gene expression. To gain insight into the FNIP1-dependent regulation of skeletal muscle energy metabolism, transcriptome analysis was performed by whole-genome gene expression profiling experiments in gastrocnemius (GC) muscle from both FNIP1-KO and FNIP1-TGKO mice. We were particularly interested in the subset of genes that were regulated only in the FNIP1-KO mice but not in FNIP1-TGKO mice. Gene ontology (GO) analysis revealed that the primary FNIP1-regulated genes were mitochondrial metabolic genes. A broad array of genes involved in mitochondria was regulated FNIP1-KO muscle in a FNIP1-dependent manner. Together, the transcriptional profiling results indicate that a significant subset of FNIP1 target genes, were those involved in mitochondrial function.

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2018-02-14 | GSE85335 | GEO

The Folliculin-Fnip1 pathway deleted in human Birt-Hogg-Dube syndrome is required for B cell development.

2012-06-16 | GSE38741 | GEO

RNAseq analysis of adipose tissue transcriptomes from wild-type and FNIP1 adipocyte specific knockout (FNIP1-AKO) mice

Project description:RNAseq analysis of adipose tissue transcriptomes from wild-type and FNIP1 adipocyte specific knockout (FNIP1-AKO) mice

| PRJNA767577 | ENA

Adipose tissue from β-3 agonist-treated mice

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Transcriptomic Characterization of Human Beige Adipocyte Differentiated From Adipose Mesenchymal Stem Cells

Project description:Beige adipocytes are a distinct type of thermogenic fat cells in human. Since beige adipocytes are distributed sporadically within white adipose, characterization of human beige adipocytes has long been a problem. In this study, we reported a rapid and roboust method in generating human beige adipocyte with chemically defined medium and RNA-Seq was perfomed to reveal the molecular characterization of derived human beige adipocytes.

2020-01-01 | GSE125331 | GEO

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Project description:The adipose tissue is a key site regulating energy metabolism. One of the contributing factors behind this is browning of white adipose tissue (WAT), however, knowledge of the intracellular determinants of browning process remains incomplete. By generating adipocyte-specific Senp2 knockout (Senp2-aKO) mice, here we showed that SENP2 negatively regulates browning by de-conjugating SUMO from C/EBPβ. Senp2-aKO mice were resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and heat production. Senp2 knockout promoted beige adipocyte accumulation in inguinal WAT by upregulation of thermogenic gene expression. In addition, SENP2 knockdown promoted thermogenic adipocyte differentiation of precursor cells isolated from inguinal and epididymal WATs. Mechanistically, sumoylated C/EBPβ, a target of SENP2, suppressed expression of HOXC10, a browning inhibitor, by recruiting a transcriptional repressor DAXX. These findings indicate that a SENP2-C/EBPβ-HOXC10 axis operates for the control of beige adipogenesis in inguinal WAT.

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