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Results: 11 to 20 of 49

Publication Record


T-bet antagonizes mSin3a recruitment and transactivates a fully methylated IFN-gamma promoter via a conserved T-box half-site.
Tong Y, Aune T, Boothby M
(2005) Proc Natl Acad Sci U S A 102: 2034-9
MeSH Terms: Binding Sites, CCAAT-Enhancer-Binding Proteins, Chromosomal Proteins, Non-Histone, DNA Methylation, DNA-Binding Proteins, Epigenesis, Genetic, Humans, Interferon-gamma, Jurkat Cells, Methyl-CpG-Binding Protein 2, Promoter Regions, Genetic, Repressor Proteins, T-Box Domain Proteins, Transcription Factors, Transcriptional Activation
Show Abstract · Added December 10, 2013
Promoter DNA methylation is a major epigenetic mechanism for silencing genes and establishing commitment in cells differentiating from their precursors. The transcription factor T-bet is a key determinant of IFN-gamma gene expression in helper T cells, but the mechanisms by which it achieves this effect are not clear. It is shown here that T-bet binds to a highly conserved T-box half-site in the IFN-gamma promoter, is recruited to the endogenous IFN-gamma promoter in T lymphoid cells, and transactivates gene expression through this sequence in a manner dependent on consensus T-box residues. This conserved promoter site is methylated in a model T cell line, and enforced T-bet expression did not alter its complete methylation. T-bet transactivated the conserved core promoter in transfection assays and collaborated functionally with C/EBPbeta despite methylation of the conserved element. Importantly, enforced T-bet expression led to dissociation of the mSin3a corepressor from the endogenous, chromatinized IFN-gamma promoter without decreasing loading of the methyl-CpG binding protein MeCP2. These data indicate that T-bet can override repressive epigenetic modification by a mechanism in which this master regulator acts through a T-box half-site to enforce the activation of IFN-gamma gene expression in part by decreased loading of a corepressor on methylated DNA.
0 Communities
2 Members
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15 MeSH Terms
Hepatic glucokinase is required for the synergistic action of ChREBP and SREBP-1c on glycolytic and lipogenic gene expression.
Dentin R, Pégorier JP, Benhamed F, Foufelle F, Ferré P, Fauveau V, Magnuson MA, Girard J, Postic C
(2004) J Biol Chem 279: 20314-26
MeSH Terms: Acetyl-CoA Carboxylase, Adenoviridae, Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Blotting, Northern, CCAAT-Enhancer-Binding Proteins, Carbohydrate Metabolism, Cell Nucleus, Cells, Cultured, DNA-Binding Proteins, Fatty Acid Synthases, Gene Expression Regulation, Glucokinase, Glucose, Glucose-6-Phosphate, Glycogen, Hepatocytes, Immunoblotting, Kinetics, Lipid Metabolism, Liver, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Microscopy, Fluorescence, Nuclear Proteins, Pentosephosphates, Proteins, Pyruvate Kinase, RNA, RNA, Messenger, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Sterol Regulatory Element Binding Protein 1, Time Factors, Transcription Factors, Transcription, Genetic
Show Abstract · Added February 23, 2011
Hepatic glucokinase (GK) catalyzes the phosphorylation of glucose to glucose 6-phosphate (G6P), a step which is essential for glucose metabolism in liver as well as for the induction of glycolytic and lipogenic genes. The sterol regulatory element-binding protein-1c (SREBP-1c) has emerged as a major mediator of insulin action on hepatic gene expression, but the extent to which its transcriptional effect is caused by an increased glucose metabolism remains unclear. Through the use of hepatic GK knockout mice (hGK-KO) we have shown that the acute stimulation by glucose of l-pyruvate kinase (l-PK), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and Spot 14 genes requires GK expression. To determine whether the effect of SREBP-1c requires GK expression and subsequent glucose metabolism, a transcriptionally active form of SREBP-1c was overexpressed both in vivo and in primary cultures of control and hGK-KO hepatocytes. Our results demonstrate that the synergistic action of SREBP-1c and glucose metabolism via GK is necessary for the maximal induction of l-PK, ACC, FAS, and Spot 14 gene expression. Indeed, in hGK-KO hepatocytes overexpressing SREBP-1c, the effect of glucose on glycolytic and lipogenic genes is lost because of the impaired ability of these hepatocytes to efficiently metabolize glucose, despite a marked increase in low K(m) hexokinase activity. Our studies also reveal that the loss of glucose effect observed in hGK-KO hepatocytes is associated with a decreased in the carbohydrate responsive element-binding protein (ChREBP) gene expression, a transcription factor suggested to mediate glucose signaling in liver. Decreased ChREBP gene expression, achieved using small interfering RNA, results in a loss of glucose effect on endogenous glycolytic (l-PK) and lipogenic (FAS, ACC) gene expression, thereby demonstrating the direct implication of ChREBP in glucose action. Together these results support a model whereby both SREBP-1c and glucose metabolism, acting via ChREBP, are necessary for the dietary induction of glycolytic and lipogenic gene expression in liver.
1 Communities
1 Members
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39 MeSH Terms
Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response.
Jiang HY, Wek SA, McGrath BC, Lu D, Hai T, Harding HP, Wang X, Ron D, Cavener DR, Wek RC
(2004) Mol Cell Biol 24: 1365-77
MeSH Terms: Activating Transcription Factor 3, Activating Transcription Factor 4, Animals, CCAAT-Enhancer-Binding Proteins, Eukaryotic Initiation Factor-2, Mice, Phosphorylation, Phosphotransferases, Protein Kinases, Protein-Serine-Threonine Kinases, RNA, Messenger, Transcription Factor CHOP, Transcription Factors, eIF-2 Kinase
Show Abstract · Added August 13, 2010
In response to environmental stress, cells induce a program of gene expression designed to remedy cellular damage or, alternatively, induce apoptosis. In this report, we explore the role of a family of protein kinases that phosphorylate eukaryotic initiation factor 2 (eIF2) in coordinating stress gene responses. We find that expression of activating transcription factor 3 (ATF3), a member of the ATF/CREB subfamily of basic-region leucine zipper (bZIP) proteins, is induced in response to endoplasmic reticulum (ER) stress or amino acid starvation by a mechanism requiring eIF2 kinases PEK (Perk or EIF2AK3) and GCN2 (EIF2AK4), respectively. Increased expression of ATF3 protein occurs early in response to stress by a mechanism requiring the related bZIP transcriptional regulator ATF4. ATF3 contributes to induction of the CHOP transcriptional factor in response to amino acid starvation, and loss of ATF3 function significantly lowers stress-induced expression of GADD34, an eIF2 protein phosphatase regulatory subunit implicated in feedback control of the eIF2 kinase stress response. Overexpression of ATF3 in mouse embryo fibroblasts partially bypasses the requirement for PEK for induction of GADD34 in response to ER stress, further supporting the idea that ATF3 functions directly or indirectly as a transcriptional activator of genes targeted by the eIF2 kinase stress pathway. These results indicate that ATF3 has an integral role in the coordinate gene expression induced by eIF2 kinases. Given that ATF3 is induced by a very large number of environmental insults, this study supports involvement of eIF2 kinases in the coordination of gene expression in response to a more diverse set of stress conditions than previously proposed.
1 Communities
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14 MeSH Terms
Regulation of alternative splicing by SRrp86 and its interacting proteins.
Li J, Hawkins IC, Harvey CD, Jennings JL, Link AJ, Patton JG
(2003) Mol Cell Biol 23: 7437-47
MeSH Terms: Adenosine Triphosphatases, Alternative Splicing, Animals, CCAAT-Enhancer-Binding Proteins, Carrier Proteins, Cell Line, DEAD-box RNA Helicases, DNA-Binding Proteins, Heterogeneous-Nuclear Ribonucleoproteins, Humans, Matrix Attachment Region Binding Proteins, Mice, NFI Transcription Factors, Nuclear Matrix-Associated Proteins, Nuclear Proteins, Nucleocytoplasmic Transport Proteins, Protein Binding, RNA Helicases, RNA, Messenger, RNA-Binding Proteins, Receptors, Estrogen, Serine-Arginine Splicing Factors, Transcription Factors, Two-Hybrid System Techniques, Y-Box-Binding Protein 1
Show Abstract · Added April 18, 2013
SRrp86 is a unique member of the SR protein superfamily containing one RNA recognition motif and two serine-arginine (SR)-rich domains separated by an unusual glutamic acid-lysine (EK)-rich region. Previously, we showed that SRrp86 could regulate alternative splicing by both positively and negatively modulating the activity of other SR proteins and that the unique EK domain could inhibit both constitutive and alternative splicing. These functions were most consistent with the model in which SRrp86 functions by interacting with and thereby modulating the activity of target proteins. To identify the specific proteins that interact with SRrp86, we used a yeast two-hybrid library screen and immunoprecipitation coupled to mass spectrometry. We show that SRrp86 interacts with all of the core SR proteins, as well as a subset of other splicing regulatory proteins, including SAF-B, hnRNP G, YB-1, and p72. In contrast to previous results that showed activation of SRp20 by SRrp86, we now show that SAF-B, hnRNP G, and 9G8 all antagonize the activity of SRrp86. Overall, we conclude that not only does SRrp86 regulate SR protein activity but that it is, in turn, regulated by other splicing factors to control alternative splice site selection.
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25 MeSH Terms
Lanosterol metabolism and sterol regulatory element binding protein (SREBP) expression in male germ cell maturation.
Fon Tacer K, Kalanj-Bognar S, Waterman MR, Rozman D
(2003) J Steroid Biochem Mol Biol 85: 429-38
MeSH Terms: Animals, CCAAT-Enhancer-Binding Proteins, DNA-Binding Proteins, Gene Expression Regulation, Lanosterol, Liver, Male, Mice, Mice, Inbred CBA, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Sexual Maturation, Spermatogenesis, Sterol Regulatory Element Binding Protein 1, Sterol Regulatory Element Binding Protein 2, Testis, Transcription Factors
Show Abstract · Added February 12, 2015
Expression of genes involved in cholesterol biosynthesis in male germ cells is insensitive to the negative cholesterol feedback regulation, in contrast to cholesterol level-sensitive/sterol regulatory element binding protein (SREBP)-dependent gene regulation in somatic cells. The role of sterol regulatory element binding proteins in spermatogenic cells was an enigma until recently, when a soluble, 55kDa cholesterol-insensitive form of SREBP2 (SREBP2gc) was discovered [Mol. Cell. Endocrinol. 22 (2002) 8478], being translated from a germ cell-specific SREBP2 mRNA. Our RT-PCR results also show that SREBP2 as well as SREBP1c mRNAs are detectable in prepubertal and postpubertal male germ cells while SREBP1a is not detected. Surprisingly, three SREBP2 immunoreactive proteins (72, 63 and 55kDa), that are not present in mouse liver nuclei, reside in testis nuclei of prepubertal and adult mice. The 55kDa protein is likely SREBP2gc, the other two isoforms are novel. HPLC measurements in liver and testes of fasted prepubertal and postpubertal mice showed no significant difference in cholesterol level. However, FF-MAS and lanosterol/testis-meiosis activating sterol (T-MAS) intermediates that are detectable mainly in testes, increase in fasted postpubertal mice which coincides well with the elevated level of 68kDa SREBP2. Similar to SREBP2gc, the two novel SREBP2 immunoreactive proteins seem to be insensitive to the level of cholesterol.
0 Communities
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17 MeSH Terms
Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling.
Yoshikawa T, Ide T, Shimano H, Yahagi N, Amemiya-Kudo M, Matsuzaka T, Yatoh S, Kitamine T, Okazaki H, Tamura Y, Sekiya M, Takahashi A, Hasty AH, Sato R, Sone H, Osuga J, Ishibashi S, Yamada N
(2003) Mol Endocrinol 17: 1240-54
MeSH Terms: Animals, Anticholesteremic Agents, CCAAT-Enhancer-Binding Proteins, Cells, Cultured, DNA-Binding Proteins, Fatty Acids, Gene Expression Regulation, Hepatocytes, Humans, Hydrocarbons, Fluorinated, Liver, Liver X Receptors, Male, Mice, Mice, Inbred C57BL, Nutritional Physiological Phenomena, Orphan Nuclear Receptors, Promoter Regions, Genetic, Pyrimidines, Rats, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Receptors, Retinoic Acid, Response Elements, Retinoid X Receptors, Signal Transduction, Sterol Regulatory Element Binding Protein 1, Sulfonamides, Transcription Factors
Show Abstract · Added March 27, 2013
Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors that form obligate heterodimers with retinoid X receptors (RXRs). These nuclear receptors play crucial roles in the regulation of fatty acid metabolism: LXRs activate expression of sterol regulatory element-binding protein 1c (SREBP-1c), a dominant lipogenic gene regulator, whereas PPARalpha promotes fatty acid beta-oxidation genes. In the current study, effects of PPARs on the LXR-SREBP-1c pathway were investigated. Luciferase assays in human embryonic kidney 293 cells showed that overexpression of PPARalpha and gamma dose-dependently inhibited SREBP-1c promoter activity induced by LXR. Deletion and mutation studies demonstrated that the two LXR response elements (LXREs) in the SREBP-1c promoter region are responsible for this inhibitory effect of PPARs. Gel shift assays indicated that PPARs reduce binding of LXR/RXR to LXRE. PPARalpha-selective agonist enhanced these inhibitory effects. Supplementation with RXR attenuated these inhibitions by PPARs in luciferase and gel shift assays, implicating receptor interaction among LXR, PPAR, and RXR as a plausible mechanism. Competition of PPARalpha ligand with LXR ligand was observed in LXR/RXR binding to LXRE in gel shift assay, in LXR/RXR formation in nuclear extracts by coimmunoprecipitation, and in gene expression of SREBP-1c by Northern blot analysis of rat primary hepatocytes and mouse liver RNA. These data suggest that PPARalpha activation can suppress LXR-SREBP-1c pathway through reduction of LXR/RXR formation, proposing a novel transcription factor cross-talk between LXR and PPARalpha in hepatic lipid homeostasis.
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1 Members
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29 MeSH Terms
Bile acid regulation of C/EBPbeta, CREB, and c-Jun function, via the extracellular signal-regulated kinase and c-Jun NH2-terminal kinase pathways, modulates the apoptotic response of hepatocytes.
Qiao L, Han SI, Fang Y, Park JS, Gupta S, Gilfor D, Amorino G, Valerie K, Sealy L, Engelhardt JF, Grant S, Hylemon PB, Dent P
(2003) Mol Cell Biol 23: 3052-66
MeSH Terms: Amino Acid Sequence, Animals, Apoptosis, Bile Acids and Salts, CASP8 and FADD-Like Apoptosis Regulating Protein, CCAAT-Enhancer-Binding Proteins, Carrier Proteins, Cell Survival, Cells, Cultured, Cyclic AMP Response Element-Binding Protein, Deoxycholic Acid, Enzyme Inhibitors, Hepatocytes, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Male, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 9, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Rats, Rats, Sprague-Dawley, Signal Transduction, Transcription Factor AP-1, fas Receptor
Show Abstract · Added March 5, 2014
Previously, we have demonstrated that deoxycholic acid (DCA)-induced signaling of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in primary hepatocytes is a protective response. In the present study, we examined the roles of the ERK and c-Jun NH(2)-terminal kinase (JNK) pathways, and downstream transcription factors, in the survival response of hepatocytes. DCA caused activation of the ERK1/2 and JNK1/2 pathways. Inhibition of either DCA-induced ERK1/2 or DCA-induced JNK1/2 signaling enhanced the apoptotic response of hepatocytes. Further analyses demonstrated that DCA-induced JNK2 signaling was cytoprotective whereas DCA-induced JNK1 signaling was cytotoxic. DCA-induced ERK1/2 activation was responsible for increased DNA binding of C/EBPbeta, CREB, and c-Jun/AP-1. Inhibition of C/EBPbeta, CREB, and c-Jun function promoted apoptosis following DCA treatment, and the level of apoptosis was further increased in the case of CREB and c-Jun, but not C/EBPbeta, by inhibition of MEK1/2. The combined loss of CREB and c-Jun function or of C/EBPbeta and c-Jun function enhanced DCA-induced apoptosis above the levels resulting from the loss of either factor individually; however, these effects were less than additive. Loss of c-Jun or CREB function correlated with increased expression of FAS death receptor and PUMA and decreased expression of c-FLIP-(L) and c-FLIP-(S), proteins previously implicated in the modulation of the cellular apoptotic response. Collectively, these data demonstrate that multiple DCA-induced signaling pathways and transcription factors control hepatocyte survival.
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26 MeSH Terms
Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes.
Amemiya-Kudo M, Shimano H, Hasty AH, Yahagi N, Yoshikawa T, Matsuzaka T, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Sato R, Kimura S, Ishibashi S, Yamada N
(2002) J Lipid Res 43: 1220-35
MeSH Terms: ATP Citrate (pro-S)-Lyase, Animals, Base Sequence, CCAAT-Enhancer-Binding Proteins, Cholesterol, DNA Primers, DNA-Binding Proteins, Enhancer Elements, Genetic, Fatty Acid Synthases, Glucokinase, Glucosephosphate Dehydrogenase, Humans, Lipids, Malate Dehydrogenase, Mice, Mice, Transgenic, Promoter Regions, Genetic, Pyruvate Kinase, Sterol Regulatory Element Binding Protein 1, Sterol Regulatory Element Binding Protein 2, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured
Show Abstract · Added March 27, 2013
Recent studies on the in vivo roles of the sterol regulatory element binding protein (SREBP) family indicate that SREBP-2 is more specific to cholesterogenic gene expression whereas SREBP-1 targets lipogenic genes. To define the molecular mechanism involved in this differential regulation, luciferase-reporter gene assays were performed in HepG2 cells to compare the transactivities of nuclear SREBP-1a, -1c, and -2 on a battery of SREBP-target promoters containing sterol regulatory element (SRE), SRE-like, or E-box sequences. The results show first that cholesterogenic genes containing classic SREs in their promoters are strongly and efficiently activated by both SREBP-1a and SREBP-2, but not by SREBP-1c. Second, an E-box containing reporter gene is much less efficiently activated by SREBP-1a and -1c, and SREBP-2 was inactive in spite of its ability to bind to the E-box. Third, promoters of lipogenic enzymes containing variations of SRE (SRE-like sequences) are strongly activated by SREBP-1a, and only modestly and equally by both SREBP-1c and -2. Finally, substitution of the unique tyrosine residue within the basic helix-loop-helix (bHLH) portion of nuclear SREBPs with arginine, the conserved residue found in all other bHLH proteins, abolishes the transactivity of all SREBPs for SRE, and conversely results in markedly increased activity of SREBP-1 but not activity of SREBP-2 for E-boxes. These data demonstrate the different specificity and affinity of nuclear SREBP-1 and -2 for different target DNAs, explaining a part of the mechanism behind the differential in vivo regulation of cholesterogenic and lipogenic enzymes by SREBP-1 and -2, respectively.
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23 MeSH Terms
Cloning and characterization of a mammalian fatty acyl-CoA elongase as a lipogenic enzyme regulated by SREBPs.
Matsuzaka T, Shimano H, Yahagi N, Yoshikawa T, Amemiya-Kudo M, Hasty AH, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Takahashi A, Yato S, Sone H, Ishibashi S, Yamada N
(2002) J Lipid Res 43: 911-20
MeSH Terms: Acyl Coenzyme A, Amino Acid Sequence, Animals, Base Sequence, CCAAT-Enhancer-Binding Proteins, Cell Line, Cloning, Molecular, DNA, Complementary, DNA-Binding Proteins, Fatty Acids, Unsaturated, Gene Expression Regulation, Enzymologic, Humans, Ligands, Liver, Mice, Mice, Transgenic, Molecular Sequence Data, Nutritional Physiological Phenomena, Sequence Alignment, Sterol Regulatory Element Binding Protein 1, Sterol Regulatory Element Binding Protein 2, Substrate Specificity, Tissue Distribution, Transcription Factors
Show Abstract · Added March 27, 2013
The mammalian enzyme involved in the final elongation of de novo fatty acid biosynthesis following the building of fatty acids to 16 carbons by fatty acid synthase has yet to be identified. In the process of searching for genes activated by sterol regulatory element-binding protein 1 (SREBP-1) by using DNA microarray, we identified and characterized a murine cDNA clone that is highly similar to a fatty acyl-CoA elongase gene family such as Cig30, Sscs, and yeast ELOs. Studies on the cells overexpressing the full-length cDNA indicate that the encoded protein, designated fatty acyl-CoA elongase (FACE), has a FACE activity specific for long-chains; C12-C16 saturated- and monosaturated-fatty acids. Hepatic expression of this identified gene was consistently activated in the livers of transgenic mice overexpressing nuclear SREBP-1a, -1c, or -2. FACE mRNA levels are markedly induced in a refed state after fasting in the liver and adipose tissue. This refeeding response is significantly reduced in SREBP-1 deficient mice. Dietary PUFAs caused a profound suppression of this gene expression, which could be restored by SREBP-1c overexpression. Hepatic FACE expression was also highly up-regulated in leptin-deficient ob/ob mice. Hepatic FACE mRNA was markedly increased by administration of a pharmacological agonist of liver X-activated receptor (LXR), a dominant activator for SREBP-1c expression. These data indicated that this elongase is a new member of mammalian lipogenic enzymes regulated by SREBP-1, playing an important role in de novo synthesis of long-chain saturated and monosaturated fatty acids in conjunction with fatty acid synthase and stearoyl-CoA desaturase.
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24 MeSH Terms
Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice.
Yahagi N, Shimano H, Hasty AH, Matsuzaka T, Ide T, Yoshikawa T, Amemiya-Kudo M, Tomita S, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Nagai R, Ishibashi S, Yamada N
(2002) J Biol Chem 277: 19353-7
MeSH Terms: Adipose Tissue, Animals, Blotting, Northern, CCAAT-Enhancer-Binding Proteins, Crosses, Genetic, DNA-Binding Proteins, Fatty Liver, Genotype, Insulin Resistance, Leptin, Lipid Metabolism, Lipoprotein Lipase, Liver, Mice, Mice, Inbred C57BL, Mice, Transgenic, Obesity, Phenotype, RNA, Messenger, Sterol Regulatory Element Binding Protein 1, Transcription Factors, Triglycerides
Show Abstract · Added March 27, 2013
Obesity is a common nutritional problem often associated with diabetes, insulin resistance, and fatty liver (excess fat deposition in liver). Leptin-deficient Lep(ob)/Lep(ob) mice develop obesity and those obesity-related syndromes. Increased lipogenesis in both liver and adipose tissue of these mice has been suggested. We have previously shown that the transcription factor sterol regulatory element-binding protein-1 (SREBP-1) plays a crucial role in the regulation of lipogenesis in vivo. To explore the possible involvement of SREBP-1 in the pathogenesis of obesity and its related syndromes, we generated mice deficient in both leptin and SREBP-1. In doubly mutant Lep(ob/ob) x Srebp-1(-/-) mice, fatty livers were markedly attenuated, but obesity and insulin resistance remained persistent. The mRNA levels of lipogenic enzymes such as fatty acid synthase were proportional to triglyceride accumulation in liver. In contrast, the mRNA abundance of SREBP-1 and lipogenic enzymes in the adipose tissue of Lep(ob)/Lep(ob) mice was profoundly decreased despite sustained fat, which could explain why the SREBP-1 disruption had little effect on obesity. In conclusion, SREBP-1 regulation of lipogenesis is highly involved in the development of fatty livers but does not seem to be a determinant of obesity in Lep(ob)/Lep(ob) mice.
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22 MeSH Terms