Abstract
Preadipocytes exposed to octanoate accumulate less lipid than cells exposed to long-chain fatty acids. This effect of octanoate involves significant attenuation of expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)gamma, steroid regulatory binding element protein (SREBP)-1c and CCAAT element binding protein (C/EBPalpha) at both the mRNA and protein levels. Expression of differentiation markers, including adipocyte fatty acid binding protein (ALBP), glycerol-3-phosphate dehydrogenase (GPDH) and leptin, was also significantly diminished by octanoate. However, octanoate did not prevent the decrease in preadipocyte factor-1 (Pref-1) expression that occurs during adipogenesis, nor did it inhibit the early induction of C/EBPbeta,delta. Treatment with synthetic PPARgamma ligands partially offset the inhibitory effect of octanoate on differentiation. Ectopic expression of PPARgamma2 in 3T3-L1 cells partially restored lipid accretion and GPDH activity in octanoate-treated cells. Adding octanoate together with troglitazone attenuated the effects of troglitazone on adipocyte differentiation in both normal 3T3-L1 cells and engineered 3T3-L1 cells that expressed ectopic PPARgamma2, implying that octanoate might compete against troglitazone for its binding to PPARgamma. These results suggest that octanoate may block adipogenesis at least in part by its influence on the expression/activation of PPARgamma.
Publication types
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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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Adipose Tissue
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Animals
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Blotting, Western
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CCAAT-Enhancer-Binding Proteins / metabolism
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Calcium-Binding Proteins
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Caprylates / pharmacology*
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Carrier Proteins / metabolism
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Cell Differentiation / drug effects*
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Cell Differentiation / physiology
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DNA-Binding Proteins / metabolism
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Fatty Acid-Binding Protein 7
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Fatty Acid-Binding Proteins
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Glycerolphosphate Dehydrogenase / metabolism
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Growth Inhibitors / metabolism*
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Intercellular Signaling Peptides and Proteins
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Leptin / metabolism
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Lipid Metabolism
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Membrane Proteins / metabolism*
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Mice
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Neoplasm Proteins*
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Nerve Tissue Proteins*
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RNA, Messenger / analysis
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Receptors, Cytoplasmic and Nuclear / drug effects
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Repressor Proteins / metabolism*
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Sterol Regulatory Element Binding Protein 1
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Transcription Factor CHOP
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Transcription Factors / drug effects
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Transcription Factors / metabolism*
Substances
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CCAAT-Enhancer-Binding Proteins
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Calcium-Binding Proteins
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Caprylates
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Carrier Proteins
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DNA-Binding Proteins
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Ddit3 protein, mouse
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Dlk1 protein, mouse
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Fabp5 protein, mouse
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Fabp7 protein, mouse
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Fatty Acid-Binding Protein 7
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Fatty Acid-Binding Proteins
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Growth Inhibitors
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Intercellular Signaling Peptides and Proteins
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Leptin
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Membrane Proteins
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Neoplasm Proteins
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Nerve Tissue 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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Srebf1 protein, mouse
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors
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Transcription Factor CHOP
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Glycerolphosphate Dehydrogenase
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glycerol-3-phosphate dehydrogenase (NAD(P)+)