Regulation of Adipogenesis by a Transcriptional Repressor That Modulates MAPK Activation

Kim, Sung Woo; Muise, Aleixo M.; Lyons, Peter J.; Ro, Hyo‐Sung

doi:10.1074/jbc.m010640200

Cited by 116 publications

(140 citation statements)

References 46 publications

Supporting

Mentioning

132

Contrasting

Order By: Relevance

“…We found for the first time that MT-II is also induced during adipocyte differentiation and that pretreatment with NAC inhibits adipocyte differentiation by reducing MT-II expression, suggesting that MT-II plays an important role in the adipocyte differentiation of 3T3L1 cells. The adipocyte differentiation of 3T3L1 cells is known to be mediated through various signal transduction pathways by hormones, growth factors, and cytokines (Ailhaud, 1997;Kim et al, 2001;Koutnikova and Auwerx, 2001). Transcription factors, such as CCAAT/enhancer binding proteins and peroxisome proliferator-activated receptors were also found to be involved in adipocyte differentiation (Holst and Grimaldi, 2002), through many different signal transduction pathways, involving, phosphatidylinositol 3-kinase (PI3K), MAPKs, cAMP, steroid hormones, and protein kinase C (Farese et al, 1992;Frevert and Kahn, 1996;Engelman et al, 1998;Aubert et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Association of anti-obesity activity of N-acetylcysteine with metallothionein-II down-regulation

Kim

Ryu²,

Chung³

et al. 2006

Exp Mol Med

View full text Add to dashboard Cite

People with upper body or visceral obesity have a much higher risk of morbidity and mortality from obesity-related metabolic disorders than those with lower body obesity. In an attempt to develop therapeutic strategies targeting visceral obesity, depotspecific differences in the expression of genes in omental and subcutaneous adipose tissues were investigated by DNA array technology, and their roles in adipocyte differentiation were further examined. We found that levels of metallothionein-II (MT-II) mRNA and protein expression were higher in omental than in subcutaneous adipose tissues. The study demonstrates that MT-II may play an important role in adipocyte differentiation of 3T3L1 preadipocytes, and that N-acetylcysteine (NAC) inhibits the adipocyte differentiation of 3T3L1 cells by repressing MT-II in a time-and dose-dependent manner. Furthermore, the intraperitoneal administration of NAC to rats and mice resulted in a reduction of body weights, and a marked reduction in visceral fat tissues. These results suggest that MT-II plays important roles in adipogenesis, and that NAC may be useful as an anti-obesity drug or supplement.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of anti-obesity activity of N-acetylcysteine with metallothionein-II down-regulation

Kim

Ryu²,

Chung³

et al. 2006

Exp Mol Med

View full text Add to dashboard Cite

show abstract

“…This inhibition could be mediated by the modulation of two proteins: AEBP-1, which binds to ERK proteins and protects them from specific phosphatases, and the phosphatase MKP-1, which inactivates ERK proteins. Indeed, AEBP-1 expression is downregulated in mature adipocytes [14], and, conversely, MKP-1 expression is augmented [15].…”

Section: The Erk Pathway In Adipogenesis: the Model Of Preadipocyte Cmentioning

confidence: 96%

The role of MAPKs in adipocyte differentiation and obesity

et al. 2005

View full text Add to dashboard Cite

that is activated and on the cellular model analysed. In addition, the duration of the stimulus can also affect the cellular response. A wide panel of different stimuli are capable to activate the MAPK pathways, but a good correlation has been found between the types of stimulus and the function assigned to the pathway. Schematically, ERK is preferentially activated by mitogens such as the serum or growth factors and, accordingly, this pathway is an important regulator of cell cycle and cell proliferation. p38 and JNK are more responsive to various stress stimuli from UV to cytokines and they have been involved in apoptosis and/or in the response to cellular stresses. Because they have been extensively studied (see for reviews [2] [3]), these general aspects will not be detailed in this review, except for their specific relevance towards adipogenesis.Regarding the process of differentiation, the role of MAPKs is extremely complex and depends on multiple parameters. The complexity is due, firstly, to the biological process itself, which, most of the time, involves different successive steps. Furthermore, each of these steps can be modulated by MAPKs leading, sometimes, to opposite effects. Probably because this complexity renders experimental models extremely sensitive, most of the tools used for Because of its essential role in cell proliferation and the fact that adipogenic stimuli, such as insulin, activate the ERK pathway, the role of this pathway in normal and pathological adipogenesis has been intensively investigated the last decade. Indeed, obesity is due to the hypertrophy of adipocytes and to the recruitment of new adipocytes from precursor cells, two processes largely dependent on regulation of adipocyte differentiation. In addition, obesity is associated with insulin resistance both in experimental models and in humans, and the role of adipose tissue and, consequently, of adipocyte differentiation is important in this pathology. Although the implication of MAPKs in insulin resistance is largely documented, our review does not discuss this aspect in details because Gual et al. review it in this series.Although much of the knowledge originates from analysis of preadipocyte cell lines, such as 3T3-L1 or 3T3-F442A, various cellular models are now available; they are summarized in figure 2.

show abstract

“…Thirty microliters of total cell extract was used to measure reporter activity by using the BMG FLUOstar Galaxy microplate reader (BMG Labtechnologies). ␤-Galactosidase assay was performed as described (17). Luciferase activity was normalized based on ␤-galactosidase activity to account for transfection efficiency.…”

Section: Reagents and Plasmidsmentioning

confidence: 99%

“…Adipocyte enhancer-binding protein 1 (AEBP1) is an 82-kDa, ubiquitously expressed transcriptional repressor that plays key regulatory roles in adipogenesis (15)(16)(17). The fact that atherosclerosis is considered a primary cause of sudden death (18), coupled with the realization that 21% and 38% of AEBP1 transgenic (AEBP1 TG ) females fed chow and a high-fat diet (HFD), respectively, undergo premature sudden death that is asymptomatic of morbidity or lethargy (unpublished data), prompted us to investigate a possible regulatory role of AEBP1 in macrophage cholesterol homeostasis and inflammation, key processes in atherogenesis.…”

mentioning

confidence: 99%

“…Hence, this set of data suggests that AEBP1 represses the expression and transcriptional activity of PPAR␥1 and LXR␣ in vitro and that this AEBP1 negative effect cannot be overcome by PPAR␥1 and LXR␣ selective agonists. The C-terminal DNA-binding domain truncation mutant form of AEBP1 (AEBP1 ⌬Sty ) was shown to be incapable of binding the AE-1 sequence that full-length AEBP1 is capable of binding (17). To examine whether PPAR␥1 and LXR␣ repression by AEBP1 requires DNA binding, the ability of AEBP1 ⌬Sty to repress these two genes was assessed.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Adipocyte enhancer-binding protein 1 is a potential novel atherogenic factor involved in macrophage cholesterol homeostasis and inflammation

Majdalawieh

Zhang

Fuki

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor ␥1 (PPAR␥1) and liver X receptor ␣ (LXR␣) play pivotal roles in macrophage cholesterol homeostasis and inflammation, key biological processes in atherogenesis. Herein we identify adipocyte enhancer-binding protein 1 (AEBP1) as a transcriptional repressor that impedes macrophage cholesterol efflux, promoting foam cell formation, via PPAR␥1 and LXR␣ down-regulation. Contrary to AEBP1 deficiency, AEBP1 overexpression in macrophages is accompanied by decreased expression of PPAR␥1, LXR␣, and their target genes ATP-binding cassette A1, ATP-binding cassette G1, apolipoprotein E, and CD36, with concomitant elevation in IL-6, TNF-␣, monocyte chemoattractant protein 1, and inducible NO synthase levels. AEBP1, but not the C-terminally truncated DNA-binding domain mutant (AEBP1 ⌬Sty ), represses PPAR␥1 and LXR␣ in vitro. Expectedly, AEBP1-overexpressing transgenic (AEBP1 TG ) macrophages accumulate considerable amounts of lipids compared with AEBP1 nontransgenic macrophages, making them precursors for foam cells. Indeed, AEBP1-overexpressing transgenic macrophages exhibit diminished cholesterol efflux compared with AEBP1 nontransgenic macrophages, whereas AEBP1-knockout (AEBP1 ؊/؊ ) macrophages exhibit enhanced cholesterol efflux compared with wild-type (AEBP1 ؉/؉ ) macrophages. Our in vitro and ex vivo experimental data strongly suggest that AEBP1 plays critical regulatory roles in macrophage cholesterol homeostasis, foam cell formation, and proinflammation. Thereby, we speculate that AEBP1 may be critically implicated in the development of atherosclerosis, and it may serve as a molecular target toward developing antiinflammatory, antiatherogenic therapeutic approaches.atherogenesis ͉ cholesterol efflux ͉ liver X receptor ␣ ͉ peroxisome proliferator-activated receptor ␥

show abstract

Regulation of Adipogenesis by a Transcriptional Repressor That Modulates MAPK Activation

Cited by 116 publications

References 46 publications

Association of anti-obesity activity of N-acetylcysteine with metallothionein-II down-regulation

Association of anti-obesity activity of N-acetylcysteine with metallothionein-II down-regulation

The role of MAPKs in adipocyte differentiation and obesity

Adipocyte enhancer-binding protein 1 is a potential novel atherogenic factor involved in macrophage cholesterol homeostasis and inflammation

Contact Info

Product

Resources

About