In pigs, adipose tissue is one of the principal organs involved in the regulation of lipid metabolism. It is particulary involved in the overall fatty acid synthesis with consequences in other lipid-target organs such as muscles and the liver. With this in mind, we have used massive, parallel high-throughput sequencing technologies to characterize the porcine adipose tissue transcriptome architecture in six Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition (three per group). High-throughput RNA sequencing was used to generate a whole characterization of adipose tissue (backfat) transcriptome. A total of 4,130 putative unannotated protein-coding sequences were identified in the 20% of reads which mapped in intergenic regions. Furthermore, 36% of the unmapped reads were represented by interspersed repeats, SINEs being the most abundant elements. Differential expression analyses identified 396 candidate genes among divergent animals for intramuscular fatty acid composition. Sixty-two percent of these genes (247/396) presented higher expression in the group of pigs with higher content of intramuscular SFA and MUFA, while the remaining 149 showed higher expression in the group with higher content of PUFA. Pathway analysis related these genes to biological functions and canonical pathways controlling lipid and fatty acid metabolisms. In concordance with the phenotypic classification of animals, the major metabolic pathway differentially modulated between groups was de novo lipogenesis, the group with more PUFA being the one that showed lower expression of lipogenic genes. These results will help in the identification of genetic variants at loci that affect fatty acid composition traits. The implications of these results range from the improvement of porcine meat quality traits to the application of the pig as an animal model of human metabolic diseases.
Analysis of porcine adipose tissue transcriptome reveals differences in de novo fatty acid synthesis in pigs with divergent muscle fatty acid composition.
Sex, Specimen part
View SamplesMitochondrial oxidative function is tightly controlled to maintain energy homeostasis in response to nutrient and hormonal signals. An important cellular component in the energy sensing response is the target of rapamycin (TOR) kinase pathway; however whether and how mTOR controls mitochondrial oxidative activity is unknown. Here, we show that mTOR kinase activity stimulates mitochondrial gene expression and oxidative function. In skeletal muscle cells and TSC2-/- MEFs, the mTOR inhibitor rapamycin largely decreased gene expression of mitochondrial transcriptional regulators such as PGC-1alpha and the transcription factors ERRalpha and NRFs. As a consequence, mitochondrial gene expression and oxygen consumption were reduced upon mTOR inhibition. Using computational genomics, we identified the transcription factor YY1 as a common target of mTOR and PGC-1alpha that controls mitochondrial gene expression. Inhibition of mTOR resulted in a failure of YY1 to interact and be coactivated by PGC-1alpha. Notably, knock-down of YY1 in skeletal muscle cells caused a significant decrease in mRNAs of mitochondrial regulators and mitochondrial genes that resulted in a decrease in respiration. Moreover, YY1 was required for rapamycin-dependent repression of mitochondrial genes. Thus, we have identified a novel mechanism in which a nutrient sensor (mTOR) balances energy metabolism via transcriptional control of mitochondrial oxidative function. These results have important implications for our understanding of how these pathways might be altered in metabolic diseases and cancer.
mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.
Age, Specimen part, Treatment
View SamplesAnalysis of brown adipose tissue from Yin Yang 1 (YY1) brown fat specific knockout mice fed a high fat diet for 3 months. YY1 deficiency in brown adipose tissue leads to strong thermogenic deficiency. The goal was to identify the genes controlled by YY1 responsible of brown fat defective function.
Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.
Age, Specimen part, Treatment
View SamplesAnalysis of visceral white adipose tissue (EWAT) from Yin Yang 1 adipose-specific knockout mice exposed to cold (4C) for 4 days.
Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.
Age, Specimen part, Treatment
View SamplesAnalysis of subcutaneous adipose tissue (IWAT) from Yin Yang 1 brown fat specific knockout mice fed a high fat diet for 2 weeks. The goal was to identify a gene signature of IWAT browning in YY1 mutant mice.
Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.
Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Specimen part, Cell line
View SamplesThe newly identified claudin-low subtype of cancer is believed to represent the most primitive breast malignancies, having arisen from transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this hypothesis, we show both in vitro and in vivo that transcription factors inducing epithelial-mesenchymal transition can drive the development of claudin-low tumors from differentiated mammary epithelial cells, by playing a dual role in cell transformation and dedifferentiation.
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Specimen part, Cell line
View SamplesThe newly identified claudin-low subtype of cancer is believed to represent the most primitive breast malignancies, having arisen from transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this hypothesis, we show both in vitro and in vivo that transcription factors inducing epithelial-mesenchymal transition can drive the development of claudin-low tumors from differentiated mammary epithelial cells, by playing a dual role in cell transformation and dedifferentiation.
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Specimen part, Cell line
View SamplesPGC1a is a transcriptional coactivator that regulates energy metabolism. PGC1a is highly expressed in a subset of melanoma tumors and cell lines. We generated gene-expression profile of control and PGC1alpha depleted A375P melanoma cells, a melanoma cell line that expresses very high levels of PGC1a to investigate the role of this gene in melanoma.
PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress.
Specimen part
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