Role of Krüppel-like Factor 15 (KLF15) in Transcriptional Regulation of Adipogenesis

Mori, Toshiyuki; Sakaue, Hiroshi; Iguchi, Haruhisa; Gomi, Hideyuki; Okada, Yuko; Takashima, Yasuhiro; Nakamura, Kyoko; Nakamura, Takehiro; Yamauchi, Toshimasa; Kubota, Naoto; Kadowaki, Tomoko; Matsuki, Yasushi; Ogawa, Wataru; Hiramatsu, Ryuji; Kasuga, Masato

doi:10.1074/jbc.m410515200

Cited by 301 publications

(251 citation statements)

References 39 publications

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“…These results imply that KLF9 might interact with other transcription factor(s) to synergistically activate PPARg2 like its family members, KLF5 18 and KLF15. 21 The result detected by the luciferase report assay showed that when KLF9 was co-transfected with C/EBPa, the two factors acted in concert to more strongly transactivate the PPARg2 promoter ( Figure 6a).…”

Section: Resultsmentioning

confidence: 99%

“…Our results are in agreement with a previous report that KLF9 overexpression does not lead to lipid accumulation in NIH3T3 cells. 21 The results from KLF9 overexpression and knockdown assays suggest that KLF9 is required but not sufficient to perform a full program of adipocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Our present results and previous works have shown that four members of the KLF family have roles in adipocyte differentiation by regulating PPARg2 transcription. 15,18,21 These KLFs are expressed sequentially during adipogenesis. KLF2 is first expressed in 3T3-L1 pre-adipocytes and its expression is shut down after differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…14 Previous reports showed that KLF proteins had different expression patterns during adipogenesis and several KLFs had been proved to either promote or inhibit this process. [15][16][17][18][19][20][21] Krü ppel-like factor 9 (KLF9), previously designated as basic transcription element-binding protein-1 (BTEB1), was initially isolated from a rat liver cDNA library. 22 KLF9 was further identified to be important for development and other physiological functions.…”

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confidence: 99%

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Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis

et al. 2010

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Krü ppel-like factors (KLFs) as a family of zinc-finger transcription factors involve in the regulation of many physiological processes. In these studies, KLF9 was characterized for its role in adipogenesis. The expression of KLF9 was markedly upregulated during the middle stage of 3T3-L1 adipocyte differentiation, and inhibition of KLF9 by RNAi impaired adipogenesis. Using promoter deletion and mutation analysis, we identified two KLF9-binding sites within the 0.6-kb region of the PPARc2 proximal promoter, indicating that KLF9 interacts with the PPARc2 promoter. Furthermore, we found that KLF9 could synergistically activate PPARc2 promoter by directly interacting with C/EBPa. In addition, overexpression of PPARc2 rescued the impairment of adipocyte differentiation induced by KLF9 knockdown, which supports that PPARc2 is a downstream target of KLF9. Collectively, our results indicate KLF9 as a key pro-adipogenic transcription factor through regulation of PPARc2 expression with C/EBPa at the middle stage of adipogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis

et al. 2010

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“…As FMIP influences myeloid differentiation as well, we examined the common key factors in both differentiation systems. One candidate is a protein belonging to the C/EBP family (Cao et al, 1991;Wang et al, 1995;Tenen et al, 1997;Lane et al, 1999), as it has been demonstrated that timely expression of C/ EBPalpha and C/EBPbeta is essential for adipocyte differentiation (Fux et al, 2004;Mori et al, 2005). Therefore, we examined the expression of C/EBPalpha and C/EBPbeta during differentiation in FMIP-overexpressing and knockdown cells.…”

Section: Fmip Influences the Expression Of C/ebpalpha Gene During Adimentioning

confidence: 99%

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

et al. 2006

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Fms interacting protein (FMIP) is a substrate for Fms tyrosine kinase, and a nuclear/cytoplasm shuttling protein with a leucine zipper. As the phosphorylation of FMIP is observed in insulin-stimulated preadipocytes, we examined the role of FMIP in adipocyte differentiation, using the mesenchymal multipotent stem cells, C2C12 cells, that can differentiate into adipocytes, muscle cells and osteoblasts. Ectopic expression of FMIP in C2C12 impairs the adipocyte differentiation induced by treatment with insulin, dexamethasone and 3-isobutyl-1-methylxanthine. These cells exhibit muscle phenotype with multinuclear morphology. Furthermore, knockdown of endogenous FMIP expression by small interfering RNA improves adipocytic lineage commitment of C2C12 cells, while impairing muscle differentiation. Upon stimulation with insulin, CCAAT/enhancer binding protein (C/EBP)-beta, but not C/EBPalpha, is upregulated in cells expressing ectopic FMIP, whereas in FMIP knockdown cells, C/EBPalpha is constitutively expressed. Ectopic expression of C/EBPalpha counteracts the effects of FMIP, whereas C/EBPalpha knockdown partially mimics the effects of FMIP in this system. Northern blot analysis and reverse transcriptase-polymerase chain reaction study reveal that ectopic FMIP-expressing cells do not contain the polyadenylated C/EBPalpha mRNA, but contain the C/EBPalpha pre-mRNA, suggesting that FMIP plays a role in RNA processing and/or export. Indeed, a member of the THO complex that plays a role in mRNA export, THOC1, is co-precipitated with FMIP. The data we have acquired on FMIP suggest that it is a target for tyrosine kinase receptors that potentiate mRNA export.

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Transcriptional Control of Adipogenesis and Fat Cell Gene Expression

White

Stephens

2010

Adipose Tissue in Health and Disease

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Overcrowded adipocytes secrete excess adipokines and cytokines under stress, which results in a deregulated metabolism. This negative response to stress increases the possibility of obesity and several of its associated diseases, such as cancer and atherosclerosis. Therefore, a reduction in the number of adipocytes may be a rational strategy to relieve the undesired expansion of adipose tissue. A newly synthesized xanthene analog, MI-401, was found to have two distinct effects on the regulation of the adipocyte's life cycle. MI-401 efficiently down regulated the expression of transcription factors, PPARγ and C/EBPα, and lipogenesis proteins, FAS and FABP4. This down regulation resulted in the inhibition of adi-pogenesis. Without newly differentiated adipocytes, the total number of adipocytes will not increase. In addition to this inhibitory effect, MI-401 was able to actively kill mature adipo-cytes. It specifically triggered apoptosis in adipocytes at low micro molar concentration and spared preadipocytes and fibroblasts. These dual functionalities make MI-401 an effective agent in the regulation of the birth and death of adipocytes.

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Role of Krüppel-like Factor 15 (KLF15) in Transcriptional Regulation of Adipogenesis

Cited by 301 publications

References 39 publications

Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis

Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

Transcriptional Control of Adipogenesis and Fat Cell Gene Expression

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