Posttranscriptional Control of Adipocyte Differentiation through Activation of Phosphoinositide 3-Kinase

Sakaue, Hiroshi; Ogawa, Wataru; Matsumoto, Michihiro; Kuroda, S.; Takata, Masafumi; Sugimoto, Takemi; Spiegelman, Bruce M.; Kasuga, Masato

doi:10.1074/jbc.273.44.28945

Cited by 144 publications

(131 citation statements)

References 39 publications

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“…EFs obtained from E14.5 embryos as described (Miki et al 2001) were induced to differentiate by treating with insulin (10 µg/mL), 250 µM DEX, and 0.5 mM IBMX in the presence of 10% fetal bovine serum for 8 d. The adenovirus vector encoding FGFR-1TR was as described (Ueno et al 1997); that encoding ␤-galactosidase was kindly provided by I. Saito (Tokyo University, Japan). Complementary DNA encoding a constitutively active form of C/EBP␤ (LAP, containing amino acids 21-296) was constructed from the mouse wild-type C/EBP␤ cDNA (kindly provided by S. Akira, Osaka University, Japan); an adenovirus vector containing this cDNA was generated with an adenovirus expression kit (Takara) as described (Sakaue et al 1998). For adenovirus-mediated gene transfer, cells cultured to subconfluency were infected with viruses at the indicated multiplicity of infection (m.o.i.).…”

Section: Cell Culture and Adenovirus Vectorsmentioning

confidence: 99%

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Requirement of fibroblast growth factor 10 in development of white adipose tissue

Sakaue¹,

Konishi²,

Ogawa³

et al. 2002

Genes Dev.

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118

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Fibroblast growth factors (FGFs) are important intercellular signaling molecules in developmental processes.Here, we show that FGF10 is secreted by cultured preadipocytes and that prevention of FGF10 signaling inhibits the expression of C/EBP␤ and the subsequent differentiation of these cells. An active form of C/EBP␤ rescued differentiation of the cells in which FGF10 signaling was blocked. Development of white adipose tissue and the expression of C/EBP␤ in this tissue of FGF10 knockout mice were markedly reduced, and the ability of embryonic fibroblasts derived from FGF10 knockout mice to differentiate into adipocytes was impaired. Therefore, FGF10 plays an important role in adipogenesis, at least partly by contributing to the expression of C/EBP␤ through an autocrine/paracrine mechanism. Received February 8, 2002; revised version accepted March 1, 2002. Adipose tissue contributes to regulation of energy balance, not only by serving as a reservoir of triglycerides but also by secreting circulating factors that affect food intake or metabolism (Hwang et al. 1997;Rosen and Spiegelman 2000;Fruebis et al. 2001;Steppan et al. 2001). Mature adipocytes do not undergo cell division; the number of these cells is therefore thought to increase as a result of the proliferation of preadipocytes and their subsequent differentiation into mature adipocytes. Various factors secreted by adipocytes or preadipocytes have been identified (Hwang et al. 1997;Rosen and Spiegelman 2000;MacDougald and Mandrup 2002), some of which, such as tumor necrosis factor-␣ (Petrunschke and Hauner 1994), Pref-1 (Smas et al. 1997), and Wnt-10b (Ross et al. 2000), regulate adipogenesis by inhibiting the differentiation of these cells. Although factors that promote the proliferation or differentiation of preadipocytes have also been shown to be secreted by such cells isolated from obese humans (Lau et al. 1987) or by mature rat adipocytes (Schillabeer et al. 1989), the nature of these factors has remained unclear.The fibroblast growth factor (FGF) family comprises at least 23 proteins (Yamashita et al. 2000;Ornitz and Itoh 2001) that function in an autocrine or paracrine manner and play important roles in the development, maintenance, and repair of tissues (Goldfarb 1996;Ornitz and Itoh 2001). FGF10 was initially identified in rat embryos by homology-based polymerase chain reaction (PCR; Yamasaki et al. 1996). Disruption of the FGF10 gene resulted in complete absence of limb bud formation and severe defects in the branching morphogenesis of the lung (Min et al. 1998;Sekine et al. 1999), indicating that FGF10 is important for development of these organs. On the other hand, we have previously shown that, among the major adult tissues, transcripts of the FGF10 gene are most abundant in adipose tissue . Brown adipose tissue (BAT) and white adipose tissue (WAT) constitute the two principal types of adipose tissue and perform distinct functions (Hwang et al. 1997;Rosen and Spiegelman 2000). The expression of FGF10 is restricted to WAT. In particular, F...

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Section: Cell Culture and Adenovirus Vectorsmentioning

confidence: 99%

“…The total RNA extracted from cells was subjected to Northern blot analysis with full-length mouse FGF10 cDNA or a fragment of mouse PPAR␥ cDNA (Sakaue et al 1998) as probes. Cell lysates (∼100 µg of protein) were subjected to immunoblot analysis as described (Sakaue et al 1998).…”

Section: Real-time Quantitative Pcr Northern Blot and Immunoblot Anmentioning

confidence: 99%

Requirement of fibroblast growth factor 10 in development of white adipose tissue

Sakaue¹,

Konishi²,

Ogawa³

et al. 2002

Genes Dev.

Self Cite

118

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“…E4 open reading frame (orf)-1 gene product of other human adenoviruses reportedly upregulates phosphatidylinositol 3-kinase (PI3K) pathway via its PDZ-protein binding domain. 18 Considering the pivotal role of PI3K in adipogenesis, 19,20 we tested the hypothesis that E4 orf-1 is the candidate gene necessary and sufficient for Ad-36-induced adipogenesis in murine and human preadipocytes.…”

Section: Introductionmentioning

confidence: 99%

Human adenovirus Ad-36 induces adipogenesis via its E4 orf-1 gene

et al. 2007

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Objective: Understanding the regulation of adipocyte differentiation by cellular and extracellular factors is crucial for better management of chronic conditions such as obesity, insulin resistance and lipodystrophy. Experimental infection of rats with a human adenovirus type 36 (Ad-36) improves insulin sensitivity and promotes adipogenesis, reminiscent of the effect of thiozolinediones. Therefore, we investigated the role of Ad-36 as a novel regulator of the adipogenic process. Design and Results: Even in the absence of adipogenic inducers, infection of 3T3-L1 preadipocytes and human adipose-derived stem cells (hASC) by Ad-36, but not Ad-2 that is another human adenovirus, modulated regulatory points that spanned the entire adipogenic cascade ranging from the upregulation of cAMP, phosphatidylinositol 3-kinase and p38 signaling pathways, downregulation of Wnt10b expression, and increased expression of CCAAT/enhancer binding protein-b and peroxisome proliferator-activated receptor g2 and consequential lipid accumulation. Next, we identified that E4 open reading frame (orf)-1 gene of the virus is necessary and sufficient for Ad-36-induced adipogenesis. Selective knockdown of E4 orf-1 by RNAi abrogated Ad-36-induced adipogenic signaling cascade in 3T3-L1 cells and hASC. Compared to the null vector, selective expression of Ad-36 E4 orf-1 in 3T3-L1 induced adipogenesis, which was abrogated when the PDZ-binding domain of the protein was deleted. Conclusion: Thus, Ad-36 E4 orf-1 is a novel inducer of rodent and human adipocyte differentiation process.

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“…A common approach when using in vitro models is to culture cells thought (or previously shown) to express adipogenesis lineage genes until they become confluent and then to apply a hormonal or xenobiotic agent 'cocktail' to 'induce' adipogenesis. Typically, these induction protocols include moderate to high concentrations of factors such as dexamethasone, methylisobutylxanthine and insulin in serumcontaining media (Wu et al, 1996;Sakaue et al, 1998;Habinowski and Witters, 2001;Croissandeau et al, 2002;Floyd and Stephens, 2003;Shin et al, 2003). Both oleic (Guo et al, 2000) and linoleic (Kang et al, 2003) acids -E-mail: rodhill@uidaho.edu were reported to induce differentiation in 3T3-L1 preadipocytes.…”

Section: Introductionmentioning

confidence: 99%

Regulation of lipid accumulation in 3T3-L1 cells: insulin-independent and combined effects of fatty acids and insulin

Kokta

Strat

Papasani

et al. 2008

Animal

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The insulin-independent and combined effects of fatty acids (FA; linoleic and oleic acids) and insulin in modulating lipid accumulation and adipogenesis in 3T3-L1 cells was investigated using a novel protocol avoiding the effects of a complex hormone 'induction' mixture. 3T3-L1 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) plus serum (control) or in DMEM plus either 0.3 mmol/l linoleic or oleic acids with 0.3 mmol/l FA-free bovine serum albumin in the presence or absence of insulin. Cells were cultured for 4 to 8 days and cell number, lipid accumulation, peroxisome proliferator-activated receptor-gamma (PPAR-g) and glucose transporter 4 (GLUT-4) protein expression were determined. Cell number appeared to be decreased in comparison with control cultures. In both oleic acid and linoleic acid-treated cells, notably in the absence (and presence) of insulin, oil-red O stain-positive cells showed abundant lipid. The percentage of cells showing lipid accumulation was greater in FA-treated cultures compared with control cells grown in DMEM plus serum (P , 0.001). Treatment with both linoleic and oleic acid-containing media evoked higher levels of PPAR-g than observed in control cultures (P , 0.05). GLUT-4 protein also increased in response to treatment with both linoleic and oleic acid-containing media (P , 0.001). Lipid accumulation in 3T3-L1 cells occurs in response to either oleic or linoleic acids independently of the presence of insulin. Both PPAR-g and GLUT-4 protein expression were stimulated. Both proteins are considered markers of adipogenesis, and these observations suggest that these cells had entered the physiological state broadly accepted as differentiated. Furthermore, 3T3-L1 cells can be induced to accumulate lipid in a serum-free medium supplemented with FA, without the use of induction protocols using complex hormone mixtures. We have demonstrated a novel model for the study of lipid accumulation that will improve the understanding of adipogenesis in adipocyte lineage cells.Keywords: adipogenesis, fatty acids, GLUT-4, insulin, PPAR-g IntroductionProgression to lipid storage in adipocytes is characterised by two distinct phases. In the first step of hyperplastic expansion, progenitor cells are thought to become committed to the adipocyte lineage, after which they cannot revert back to a less differentiated 'stem-like' cell (Thompson et al., 1998;Boone et al., 2000). Once committed, adipoblasts undergo an exponential replication phase that terminates and the cell cycle arrests at gap 1 (G1). Early markers of differentiation, such as lipoprotein lipase (LPL) are then expressed, and these cells, known as preadipocytes, may then undergo proliferation (Boone et al., 2000). After preadipocytes stop proliferating, late markers of differentiation, such as glycerol-3-phosphate dehydrogenase (GPDH) and fatty acid synthetase (FAS) are detected. Cells then begin lipid accumulation in the cytosol at which time cells are termed adipocytes (Boone et al., 2000).Much of our understanding of these proc...

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Posttranscriptional Control of Adipocyte Differentiation through Activation of Phosphoinositide 3-Kinase

Cited by 144 publications

References 39 publications

Requirement of fibroblast growth factor 10 in development of white adipose tissue

Requirement of fibroblast growth factor 10 in development of white adipose tissue

Human adenovirus Ad-36 induces adipogenesis via its E4 orf-1 gene

Regulation of lipid accumulation in 3T3-L1 cells: insulin-independent and combined effects of fatty acids and insulin

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