The uptake, biosynthesis and metabolism of cholesterol and other lipids are exquisitely regulated by feedback and feed-forward pathways in organisms ranging from Caenorhabditis elegans to humans. As endoplasmic reticulum (ER) membrane-embedded transcription factors that are activated in the Golgi apparatus, sterol regulatory element-binding proteins (SREBPs) are central to the intracellular surveillance of lipid catabolism and de novo biogenesis. The biosynthesis of SREBP proteins, their migration from the ER to the Golgi compartment, intra-membrane proteolysis, nuclear translocation and trans-activation potential are tightly controlled in vivo. Here we summarize recent studies elucidating the transcriptional and post-transcriptional regulation of SREBP-1c through nutrition and the action of hormones, particularly insulin, and the resulting implications for dyslipidemia of obesity, metabolic syndrome and type 2 diabetes.
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Environmentally relevant concentrations of oxytetracycline and copper increased liver lipid deposition through inducing oxidative stress and mitochondria dysfunction in grass carp Ctenopharyngodon idella.
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Oxytetracycline (OTC) and Cu are prevalent in aquatic ecosystems and their pollution are issues of serious concern. The present working hypothesis is that the toxicity of Cu and OTC mixture on physiological activity of fish was different from single OTC and Cu alone. The present study indicated that, compared to single OTC or Cu alone, Cu+OTC mixture reduced growth performance and feed utilization of grass carp, escalated the contents of Cu, OTC and TG, increased lipogenesis, induced oxidative stress, damaged the mitochondrial structure and functions and inhibited the lipolysis in the liver tissues and hepatocytes of grass carp.
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INSERM U870, INRA UMR1235, Régulations Métaboliques, Nutrition, et Diabètes, Université Lyon 1, Faculté de Médecine Lyon-Sud, Oullins, INSA-Lyon, RMND, Villeurbanne, Lyon, France.
In this study we have identified the target genes of sterol regulatory element binding protein (SREBP)-1a and SREBP-1c in primary cultures of human skeletal muscle cells, using adenoviral vectors expressing the mature nuclear form of human SREBP-1a or SREBP-1c combined with oligonucleotide microarrays. Overexpression of SREBP-1a led to significant changes in the expression of 1,315 genes (655 upregulated and 660 downregulated), whereas overexpression of SREBP-1c modified the mRNA level of 514 genes (310 upregulated and 204 downregulated). Gene ontology analysis indicated that in human muscle cells SREBP-1a and -1c are involved in the regulation of a large number of genes that are at the crossroads of different functional pathways, several of which are not directly connected with cholesterol and lipid metabolism.
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Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA.
The uptake, biosynthesis and metabolism of cholesterol and other lipids are exquisitely regulated by feedback and feed-forward pathways in organisms ranging from Caenorhabditis elegans to humans. As endoplasmic reticulum (ER) membrane-embedded transcription factors that are activated in the Golgi apparatus, sterol regulatory element-binding proteins (SREBPs) are central to the intracellular surveillance of lipid catabolism and de novo biogenesis. The biosynthesis of SREBP proteins, their migration from the ER to the Golgi compartment, intra-membrane proteolysis, nuclear translocation and trans-activation potential are tightly controlled in vivo.
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INSERM, U671, Paris F-75270, France.
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