Transcriptional activation of Cidec by PPARγ2 in adipocyte

Kim, Yoon-Jin; Cho, Si Young; Yun, Cheol Hee; Moon, Yeonsil; Lee, Tae Ryong; Kim, Sang Hoon

doi:10.1016/j.bbrc.2008.09.129

Cited by 57 publications

(45 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, downregulation of FSP27 transcripts by TNF-␣ could be partly due to a decrease in C/ EBP ␣ levels ( 20,24,47 ). It has also been shown that transcription of FSP27 is PPAR ␥ -dependent in hepatocytes ( 48 ) and adipocytes ( 18,49 ) and that the effect of TNF-␣ on FSP27 transcription could be due to the previously observed decrease in PPAR ␥ protein levels in TNF-␣ -treated adipocytes ( 50,51 ). TNF-␣ has also been reported to regulate lipolysis in 3T3-L1 adipocytes through mitogen-activated protein kinases ( 52 ); however, inhibition of these kinases was not able to block the depletion of FSP27 transcripts ( 20 ).…”

Section: Ubiquitination Of Fsp27 In Response To Tnf-␣ and Isoproterenolmentioning

confidence: 99%

Regulation of fat specific protein 27 by isoproterenol and TNF-α to control lipolysis in murine adipocytes

Ranjit

Boutet

Gandhi

et al. 2011

Journal of Lipid Research

View full text Add to dashboard Cite

Storing excess energy for future use during starvation is critical for the survival of mammals. Much of this energy is stored in the form of triacylglycerol (TAG) within lipid droplets, which are present most abundantly in adipocytes and which, in turn, accumulate in depots such as subcutaneous and visceral adipose tissue in mice and humans. TAG in lipid droplets is mobilized during starvation by lipase-catalyzed hydrolysis (lipolysis) to release energy in the forms of glycerol and free fatty acids, providing fuel to other cell types such as muscle and liver. Previous work investigating formation of lipid droplets and regulation of lipolysis has elucidated the importance of lipid dropletassociated proteins for these processes ( 1, 2 ). Based on shared sequence homology, one set of lipid droplet proteins is grouped as the perilipin-adipophilin-tail interacting protein 47 (PAT/TIP47) family of proteins ( 3 ). PAT-related proteins are functionally conserved from mammals to lower organisms such as Drosophila and Dictyostelium spp ( 4 ). In Drosophila , two PAT domain proteins are encoded by the Lsdp1 and Lsd2 genes. Drosophila loss-of-function Lsd2 mutants are lean, whereas Lsd2 overexpression causes obesity ( 5 ). In mammals, PAT proteins can be divided into exchangeable TAG-associated PAT proteins (EPATs) or constitutively TAG-associated PAT proteins (CPATs). EPATs include the TIP47/perilipin-3 (PLIN3), S3-12/PLIN4, and Abstract The lipid droplet-associated fat specifi c protein 27 (FSP27) suppresses lipolysis and thereby enhances triglyceride accumulation in adipocytes. We and others have recently found FSP27 to be a remarkably short-lived protein (half-life, 15 min) due to its rapid ubiquitination and proteasomal degradation. Thus, we tested the hypothesis that lipolytic agents such as tumor necrosis factor-␣ (TNF-␣ ) and isoproterenol modulate FSP27 levels to regulate FFA release. Consistent with this concept, we showed that the lipolytic actions of TNF-␣ , interleukin-1 ␤ (IL-1 ␤ ), and IFN-␥ are accompanied by marked decreases in FSP27 expression and lipid droplet size in mouse adipocytes. Similar depletion of FSP27 using short interfering RNA (siRNA) mimicked the lipolysis-enhancing effect of TNF-␣ , while maintaining stable FSP27 levels using expression of hemagglutinin epitopetagged FSP27 blocked TNF-␣ -mediated lipolysis. In contrast, we show the robust lipolytic action of isoproterenol is paradoxically associated with increases in FSP27 levels and a delayed degradation rate corresponding to decreased ubiquitination. This catecholamine-mediated increase in FSP27 abundance, probably a feedback mechanism for restraining excessive lipolysis by catecholamines, is mimicked by forskolin or 8-bromo-cAMP treatment and is prevented by the protein kinase A (PKA) inhibitor KT5720 or by PKA depletion using siRNA. Taken together, these data identify the regulation of FSP27 as an important intermediate in the mechanism of lipolysis in adipocytes in response to TNF-␣ and isoproterenol. -Ranjit, S

show abstract

Section: Ubiquitination Of Fsp27 In Response To Tnf-␣ and Isoproterenolmentioning

confidence: 99%

Regulation of fat specific protein 27 by isoproterenol and TNF-α to control lipolysis in murine adipocytes

Ranjit

Boutet

Gandhi

et al. 2011

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Similarly, CIDEA is regulated, at least in the liver, by PPAR [71], although in adipose tissue ERR and the balance between the coregulators PGC-1 and RIP140 is more likely to be important for determination of its expression level [34]. PPAR seems to be most important for the expression of CIDEC [72] and ATGL [73,74]. Furthermore, a positive feedback loop may be facilitated by the products of lipolysis, due to ATGL, acting as ligands for PPARs [75].…”

Section: Effect Of Cold Exposure On Ld Protein Gene Expressionmentioning

confidence: 99%

Dynamic changes in lipid droplet-associated proteins in the “browning” of white adipose tissues

Barneda

Frontini

Cinti

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

HighlightsLipid droplet proteins are more highly expressed in BAT than WAT Cold acclimatization induces Cidea, Gyk and pro-lipolytic proteins in WAT -adrenergic induction of lipid droplet formation and growth by lipid transfer Thermogenic potential of the futile cycle of TAG hydrolysis and re-synthesis Role of lipid droplet remodelling in unilocular to multilocular adipocyte transition AbstractThe morphological and functional differences between lipid droplets (LDs) in brown (BAT) and white (WAT) adipose tissue will largely be determined by their associated proteins. Analysing mRNA expression in mice fat depots we have found that most LD protein genes are expressed at higher levels in BAT, with the greatest differences observed for Cidea and Plin5. Prolonged cold exposure, which induces the appearance of brown-like adipocytes in mice WAT depots, was accompanied with the potentiation of the lipolytic machinery, with changes in ATGL, CGI-58 and G0S2 gene expression.However the major change detected in WAT was the enhancement of Cidea mRNA.Together with the increase in Cidec, it indicates that LD enlargement through LD-LD transference of fat is an important process during WAT browning. To study the dynamics of this phenotypic change, we have applied 4D confocal microscopy in differentiated 3T3-L1 cells under sustained -adrenergic stimulation. Under these conditions the cells experienced a LD remodelling cycle, with progressive reduction on the LD size by lipolysis, followed by the formation of new LDs, which were subjected to an enlargement process, likely to be CIDE-triggered, until the cell returned to the basal state. This transformation would be triggered by the activation of a thermogenic futile cycle of lipolysis/lipogenesis and could facilitate the molecular mechanism for the unilocular to multilocular transformation during WAT browning.

show abstract

“…The characteristics of the primary human hepatocytes and their upregulated by K-877 treatment are involved in carbohydrate and lipid metabolism (Table 3), of which Cyp4a31 19) , Pdk4 12) , Cidec 20) , Acot1 21) , Acot2 22) , Acot3 23) , Slc27a1 (FATP1) 13) , Vnn1 24,25) and Aqp3 26) have been reported to be PPARs target genes. On the other hand, K-877 treatment reduced the expression of phase enzymes and xenobiotic transporters, such as the Slco1a4, Sult1a1, Slc22a7 and Cyp2c54 genes 27) ( Table 4).…”

Section: K-877 Regulates Fatty Acid Metabolic Genes In Primary Human mentioning

confidence: 99%

Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (SPPARMα))-Regulated Genes in Primary Human Hepatocytes and the Mouse Liver

Raza-Iqbal

Tanaka

Anai

et al. 2015

JAT

View full text Add to dashboard Cite

Aim: Selective PPAR modulators (SPPARM ) are under development for use as next-generation lipid lowering drugs. In the current study, to predict the pharmacological and toxicological effects of a novel SPPARM K-877, comprehensive transcriptome analyses of K-877-treated primary human hepatocytes and mouse liver tissue were carried out. Methods: Total RNA was extracted from the K-877 treated primary human hepatocytes and mouse liver and adopted to the transcriptome analysis. Using a cluster analysis, commonly and species specifically regulated genes were identified. Also, the profile of genes regulated by K-877 and fenofibrate were compared to examine the influence of different SPPARM on the liver gene expression. Results: Consequently, a cell-based transactivation assay showed that K-877 activates PPAR with much greater potency and selectivity than fenofibric acid, the active metabolite of clinically used fenofibrate. K-877 upregulates the expression of several fatty acid -oxidative genes in human hepatocytes and the mouse liver. Almost all genes up-or downregulated by K-877 treatment in the mouse liver were also regulated by fenofibrate treatment. In contrast, the K-877-regulated genes in the mouse liver were not affected by K-877 treatment in the Ppara-null mouse liver. Depending on the species, the peroxisomal biogenesis-related gene expression was robustly

show abstract

Transcriptional activation of Cidec by PPARγ2 in adipocyte

Cited by 57 publications

References 28 publications

Regulation of fat specific protein 27 by isoproterenol and TNF-α to control lipolysis in murine adipocytes

Regulation of fat specific protein 27 by isoproterenol and TNF-α to control lipolysis in murine adipocytes

Dynamic changes in lipid droplet-associated proteins in the “browning” of white adipose tissues

Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (SPPARMα))-Regulated Genes in Primary Human Hepatocytes and the Mouse Liver

Contact Info

Product

Resources

About