Abstract
We have examined gene expression in the fat tissue of normal mice at the onset of diet-induced obesity. Insulin-induced gene 1 (insig-1) mRNA rose progressively with a high-fat diet and declined on a restricted diet. Because insig-1 binds sterol regulatory element-binding protein cleavage-activating protein in the endoplasmic reticulum, thereby blocking proteolytic processing required for sterol regulatory element-binding protein activation, we tested its influence on lipogenesis. In differentiating 3T3-L1 cells, insig-1 and -2 rose in parallel with aP2 mRNA during differentiation. The mRNA of the lipogenic transcription factor, carbohydrate response element-binding protein, was undetectable in undifferentiated 3T3-L1 preadipocytes but rose dramatically during differentiation in 25 mM, but not in 5 mM, glucose. Transfection of mouse or human insig-1 into 3T3-L1 preadipocytes completely prevented oil red O staining and blocked upregulation of aP2, peroxisome proliferator-activated receptor gamma2, and carbohydrate response element-binding protein, while reducing down-regulation of preadipocyte factor 1. The results suggest that insig-1 expression restricts lipogenesis in mature adipocytes and blocks differentiation in preadipocytes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Adipocytes / cytology*
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Adipocytes / metabolism*
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Animals
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Azo Compounds / pharmacology
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Blotting, Northern
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Calcium-Binding Proteins
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Carbohydrate Metabolism
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Cell Differentiation
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Cell Division
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Coloring Agents / pharmacology
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DNA, Complementary / metabolism
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DNA-Binding Proteins / metabolism
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Diet
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Down-Regulation
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Glucose / metabolism
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Glucose / pharmacology
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Humans
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins / metabolism
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Mice
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Obesity / genetics
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Plasmids / metabolism
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Protein Binding
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Proteins / metabolism
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Proteins / physiology*
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RNA, Messenger / metabolism
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Radioimmunoassay
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Receptors, Cytoplasmic and Nuclear / metabolism
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Repressor Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Transcription Factors / metabolism
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Transfection
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Up-Regulation
Substances
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Azo Compounds
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Calcium-Binding Proteins
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Coloring Agents
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DLK1 protein, human
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DNA, Complementary
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DNA-Binding Proteins
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Dlk1 protein, mouse
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Dlk1 protein, rat
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INSIG1 protein, human
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Insig1 protein, rat
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Mlxipl protein, rat
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Proteins
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Repressor Proteins
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Transcription Factors
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oil red O
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Glucose