Molecular regulation of adipocyte differentiation

Cowherd, Robert M.; Lyle, Robert; McGehee, Robert E.

doi:10.1006/scdb.1998.0276

Cited by 253 publications

(202 citation statements)

References 0 publications

Supporting

Mentioning

193

Contrasting

Unclassified

Order By: Relevance

“…The differentiation of preadipocytes is a complex process that includes a cascade of transcriptional events that culminate in the expression of C/EBPs, proliferator-activated receptor-g and adipocyte determination-and differentiationdependent factor 1 in rodent or sterol regulatory elementbinding protein-1 in humans. 20,36 Subsequently, these vital transcription factors mediated the transcriptional control of relative genes that were required for the conversion of preadipocytes to adipocytes. Previous studies have indicated that antisense RNA against the mRNA of C/EBPa suppressed the differentiation of preadipocytes, whereas the ectopic expression of C/EBPa promoted this process.…”

Section: Agt Knockdown Inhibits Hpa-v Differentiation Z-w Ye Et Almentioning

confidence: 99%

“…37,38 It was shown that C/EBPa activated several genes, such as AGT, adipocyte protein-2 and stearoyl-CoA desaturase during preadipocytes differentiation. 36,39 Ang II, uniquely generated from AGT, could stimulate the production and release of prostacyclin, which promotes the process of preadipocytes differentiation subsequently. 40 It was suggested that Ang II is implicated in preadipocytes differentiation by increasing TAG content and lipogenic enzymes activity significantly.…”

Section: Agt Knockdown Inhibits Hpa-v Differentiation Z-w Ye Et Almentioning

confidence: 99%

See 1 more Smart Citation

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Jiang

2009

Int J Obes

View full text Add to dashboard Cite

Objective: The immediate cause of obesity is the massive deposition of subcutaneous and visceral fat attributing to the continuous proliferation and differentiation of preadipocytes. The identification of the underlying molecular mechanisms of preadipocytes differentiation is urgent, and will have an important role in plastic and reconstructive surgical procedures. Methods: Two small hairpin RNA (shRNA)-mediated RNA interference plasmids have been constructed on the basis of the activity of H1 promoter-driven expression vector psiRNA-hH1neo to suppress the expression of angiotensinogen (AGT) in human preadipocytes-visceral (HPA-v). Subsequently, glycerol-3-phosphate dehydrogenase (G3PDH) activity and intracytoplasmic lipids content were detected during the process of HPA-v differentiation. Results: Small hairpin RNA-expressing vectors have been successfully constructed to suppress the expression of AGT significantly. Both intracytoplasmic lipids content and G3PDH activity decreased to a certain extent compared with that in the control group in the whole process of HPA-v differentiation. Conclusions: Two shRNA-mediated AGT-targeting plasmids inhibited the process of HPA-v differentiation to a certain extent. However, the accumulation of intracytoplasmic lipids was not exclusively determined by the expression of AGT, and it may also be regulated by other factors. In conclusion, this study provided a method to inhibit the process of preadipocytes differentiation, and it may have a role in obesity treatment and adipose tissue engineering application.

show abstract

Section: Agt Knockdown Inhibits Hpa-v Differentiation Z-w Ye Et Almentioning

confidence: 99%

Section: Agt Knockdown Inhibits Hpa-v Differentiation Z-w Ye Et Almentioning

confidence: 99%

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Jiang

2009

Int J Obes

View full text Add to dashboard Cite

show abstract

“…The expression of TNF-a is observed in 3T3-L1 preadipocytes, and declines gradually after the beginning of maturation in the presence of inducers. 21 The mice with transplanted cultured 3T3-L1 cells showed that the transplanted adipocytes in visceral space, and not subcutaneous space, secret TNF-a and the secreted molecules actually disturb the systemic insulin sensitivity, based on the decreased insulin action in tissues. 5 The induced expression of TNF-a is also observed in the adipocytes in visceral spaces of subcutaneously lipectomized mice.…”

Section: Discussionmentioning

confidence: 99%

Macrophages regulate tumor necrosis factor-α expression in adipocytes through the secretion of matrix metalloproteinase-3

et al. 2008

View full text Add to dashboard Cite

Objective: Adipocytes accumulated in the visceral area change their function to induce tumor necrosis factor-a (TNF-a) secretion with concomitant matrix metalloproteinase (MMP)-3 induction in mice. This study was performed to clarify the role of macrophages (Mf)-secreted MMP on the functional changes in adipocytes using a culture system. Design: Cultures of 3T3-L1 adipocytes with THP-1 Mf or the Mf-conditioned medium were used to investigate the role of Mf-MMP on the TNF-a gene in 3T3-L1 adipocytes by the addition of MMP inhibitors. For animal experiments, male C57BL/6J mice were rendered insulin resistant by feeding a high-fat diet, and the expression of an Mf marker F4/80, and MMP-3 genes in mesenteric and subcutaneous fat tissue specimens were examined. Results: Mf-conditioned media (Mf-CM) increased the levels of TNF-a mRNA expression in 3T3-L1 adipocytes, and these adipocyte responses were abolished by treatment with GM6001, a broad-spectrum MMP inhibitor, or NNGH (N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid), an MMP-3 inhibitor. The activated form of MMP-3 enhanced glycerol release as well as TNF-a protein secretion from 3T3-L1 adipocytes. The incubation of adipocytes with MMP-3 inhibited insulin-induced glucose uptake in adipocytes. Furthermore, a high-fat intake increased the expression of MMP-3, decreased the insulin-induced glucose uptake of adipocytes and induced expression of F4/80 in mesenteric fat tissue of C57BL/6 mice. Conclusion: Mf may cause a pathological link with surrounding adipocytes through the secretion of MMP-3 followed by TNF-a expression in adipocytes in visceral fat tissue.

show abstract

“…Once preadipocytes have undergone MCE, they next exit the cell cycle and undergo terminal adipocyte differentiation, a step believed to be controlled by changes in the expression of a variety of cell cycle regulatory proteins including cyclin-dependent kinase inhibitors and members of the retinoblastomarelated family of proteins [Richon et al, 1997;Cowherd et al, 1999;Morrison and Farmer, 1999]. As shown in Figure 4B, MDI treatment of 3T3-L1 preadipocytes resulted in the expected time-dependent increase in expression of both p21 and p27, whose expression has previously been shown to correlate with the commitment of differentiating preadipocytes to terminal differentiation [Morrison and Farmer, 1999].…”

Section: The Pgf2a-calcineurin Signaling Pathway Does Not Interfere Wmentioning

confidence: 99%

Prostaglandin F2α inhibits adipocyte differentiation via a Gαq‐Calcium‐Calcineurin‐Dependent signaling pathway

Liu

Clipstone

2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

Prostaglandin F2a (PGF2a) is a potent physiological inhibitor of adipocyte differentiation, however the specific signaling pathways and molecular mechanisms involved in mediating its anti-adipogenic effects are not well understood. In the current study, we now provide evidence that PGF2a inhibits adipocyte differentiation via a signaling pathway that requires heterotrimeric G-protein Gaq subunits, the elevation of the intracellular calcium concentration ([Ca 2þ ] i ), and the activation of the Ca 2þ /calmodulin-regulated serine/threonine phosphatase calcineurin. We show that while this pathway acts to inhibit an early step in the adipogenic cascade, it does not interfere with the initial mitotic clonal expansion phase of adipogenesis, nor does it affect either the expression, DNA binding activity or differentiation-induced phosphorylation of the early transcription factor C/EBPb. Instead, we find that PGF2a inhibits adipocyte differentiation via a calcineurin-dependent mechanism that acts to prevent the expression of the critical pro-adipogenic transcription factors PPARg and C/EBPa. Furthermore, we demonstrate that the inhibitory effects of PGF2a on both the expression of PPARg and C/EBPa and subsequent adipogenesis can be attenuated by treatment of preadipocytes with the histone deacetylase (HDAC) inhibitor trichostatin A. Taken together, these results indicate that PGF2a inhibits adipocyte differentiation via a Gaq-Ca 2þ -calcineurin-dependent signaling pathway that acts to block expression of PPARg and C/EBPa by a mechanism that appears to involves an HDAC-sensitive step.

show abstract

Molecular regulation of adipocyte differentiation

Cited by 253 publications

References 0 publications

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Macrophages regulate tumor necrosis factor-α expression in adipocytes through the secretion of matrix metalloproteinase-3

Prostaglandin F2α inhibits adipocyte differentiation via a Gαq‐Calcium‐Calcineurin‐Dependent signaling pathway

Contact Info

Product

Resources

About