SREBPs: Global Regulator of Lipid Metabolism

Wed, 04/10/2013 - 08:14

Sterol regulatory element binding proteins (SREBPs) are indirectly required for cholesterol biosynthesis and for uptake and fatty acid biosynthesis. There are three known SREBP isoforms, SREBP1a, 1c and SREBP2; these have different roles in lipid synthesis. In vivo studies using transgenic and knockout mice suggest that SREBP-1c is involved in FA synthesis and insulin induced glucose metabolism, whereas SREBP-2 is relatively specific to cholesterol synthesis. The SREBP-1a isoform seems to be implicated in both pathways (1). Intracellular SREBPs can be modulated by different nutritional and hormonal cues at several levels, including transcription, translation, processing (maturation) and degradation. Intracellular processing of SREBP1A and SREBP2 could be stimulated by depletion of cellular sterol content (2).

Western Blot: SREBP1 Antibody Western Blot: SREBP1 Antibody

Recently it has been demonstrated that the knockdown of SREBP-1 mRNA using a RNA-interference technique totally abrogated the glucose-induced upregulation of lipogenic enzymes, indicating that SREBP-1c mediates the action of glucose on these genes in rat skeletal muscle (3). These observations suggest that glucose rapidly stimulates SREBP-1c maturation leading to the increased intramuscular lipid accumulation associated with muscle insulin resistance in obesity or type-2 diabetes arising partly from de novo fatty acid synthesis in the skeletal muscles. A new chapter towards the better understanding of the molecular mechanisms regulating de-novo lipogenesis and a better comprehension of these mechanisms will be the key for the development of new tools to treat several hormonal related complications.

  1. PMID: 15589694
  2. PMID: 11591434
  3. PMID: 15039461


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