X‐box binding protein 1 enhances adipogenic differentiation of 3T3‐L1 cells through the downregulation of Wnt10b expression

Cho, Yoon Mi; Kim, Dae Hun; Kwak, Su-Nam; Jeong, Seong-Whan; Kwon, Oh-Joo

doi:10.1016/j.febslet.2013.04.005

Cited by 19 publications

(26 citation statements)

References 26 publications

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“…L). Although the importance of XBP1s in in vitro adipogenesis has been suggested previously , our findings from XBP1s over‐expression experiments in wild‐type and XBP1‐KD cells and the quantitative measurement of intracellular triacylglycerol contents more reliably suggest that XBP1s is an essential pro‐adipogenic transcription factor, especially in the very early time period of differentiation.…”

Section: Resultssupporting

confidence: 52%

“…Given that C/EBPα and Wnt10b, two important regulators for adipogenesis, are target genes of XBP1s , it is plausible that XBP1s may direct adipogenesis by regulation of pro‐ and anti‐adipogenic signalling pathways. Moreover, to our knowledge, in vitro adipogenesis is always suppressed by depletion of XBP1s . Taken together, these findings imply that XBP1s may also play roles in adipose tissue formation in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…During the UPR, XBP1s restores homeostasis in the endoplasmic reticulum, and also plays a role in many processes such as cell differentiation [12][13][14][15][16], regulation of immune responses [17], hepatic lipogenesis [18] and lactation [19]. Recently, a possible role of XBP1s in adipogenesis has been suggested based on the increase in XBP1s during in vitro adipogenesis [8,10,19,20] and the suppression of adipogenesis by depletion of XBP1s [8,10,19,21]. In the mechanistic studies, CCAAT/enhancer-binding protein a (C/EBPa) was identified as a target of XBP1s [10], and we also suggested that suppression of Wnt10b/b-catenin signalling is a possible pro-adipogenic mechanism of XBP1s [21].…”

Section: Introductionmentioning

confidence: 99%

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X‐box binding protein 1 is a novel key regulator of peroxisome proliferator‐activated receptor γ2

et al. 2014

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X‐box binding protein 1 (XBP1), a transcription factor of the unfolded protein response, plays various roles in many biological processes. We examined its pro‐adipogenic activity and target genes during adipogenic differentiation in wild‐type and genetically modified 3T3‐L1 cells. Signalling pathways that contribute to Xbp1 mRNA splicing, and the correlation of the transcriptionally active XBP1 isoform (XBP1s) level with body mass index and the level of peroxisome proliferator‐activated receptor γ2 (PPARγ2) in human adipose tissues were also examined. The mRNA and nuclear protein expression levels of XBP1s increased immediately following hormonal induction of adipogenesis, reaching a peak at 6 h. Results from cDNA microarray and gene expression analyses using genetically modified cells indicated that PPARγ2 was a principal target of XBP1s. The XBP1s‐specific binding motif, which is distinct from the CCAAT/enhancer‐binding protein α binding site, was identified in the PPARγ2 promoter by site‐directed mutagenesis. Fetal bovine serum, insulin, 3‐isobutyl‐1‐methylxanthine and dexamethasone contributed independently to Xbp1 mRNA splicing. In human subcutaneous adipose tissues, the levels of both Xbp1s and Pparγ2 mRNA increased proportionally with body mass index, and there was a significant positive correlation between the two genes. These data suggest for the first time that positive regulation of PPARγ2 is a principal mechanism of XBP1s‐mediated adipogenesis in 3T3‐L1 cells.

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Section: Resultssupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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X‐box binding protein 1 is a novel key regulator of peroxisome proliferator‐activated receptor γ2

et al. 2014

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“…In vitro, we and others have shown that XBP1s is required (10–12), but not sufficient (13) for adipocyte differentiation (i.e., adipogenesis). In vivo, Xbp1 +/− mice exhibit increased IRE1α activation in adipose tissue upon obesity, which subsequently attenuates insulin signaling by modulating the Jun NH 2 -terminal kinase–insulin receptor substrate-1 signaling axis (4).…”

Section: Introductionmentioning

confidence: 85%

“…It has been implicated in the ER expansion in differentiating plasma cells (43,44) and the pancreas and salivary glands (45), gluconeogenesis and lipogenesis in hepatocytes (5–7,46), adipogenesis (10–12), inflammation in macrophages (47) and Paneth cells (48), and control of autophagy in the nervous system (49). Our data further highlight an important role of XBP1s in adiponectin complex formation in adipocytes.…”

Section: Discussionmentioning

confidence: 99%

Adipocyte Spliced Form of X-Box–Binding Protein 1 Promotes Adiponectin Multimerization and Systemic Glucose Homeostasis

et al. 2014

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The physiological role of the spliced form of X-box–binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. In this study, we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of high-molecular-weight adiponectin and, indeed, is adiponectin-dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription, likely through a direct regulation of the expression of several ER chaperones involved in adiponectin maturation, including glucose-regulated protein 78 kDa, protein disulfide isomerase family A, member 6, ER protein 44, and disulfide bond oxidoreductase A–like protein. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia.

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Transcriptional Regulation of Adipogenesis

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Richard

Hang

et al. 2017

Comprehensive Physiology

295

153

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Adipocytes are the defining cell type of adipose tissue. Once considered a passive participant in energy storage, adipose tissue is now recognized as a dynamic organ that contributes to several important physiological processes, such as lipid metabolism, systemic energy homeostasis, and whole-body insulin sensitivity. Therefore, understanding the mechanisms involved in its development and function is of great importance. Adipocyte differentiation is a highly orchestrated process which can vary between different fat depots as well as between the sexes. While hormones, miRNAs, cytoskeletal proteins, and many other effectors can modulate adipocyte development, the best understood regulators of adipogenesis are the transcription factors that inhibit or promote this process. Ectopic expression and knockdown approaches in cultured cells have been widely used to understand the contribution of transcription factors to adipocyte development, providing a basis for more sophisticated in vivo strategies to examine adipogenesis. To date, over two dozen transcription factors have been shown to play important roles in adipocyte development. These transcription factors belong to several families with many different DNA-binding domains. While peroxisome proliferator-activated receptor gamma (PPARγ) is undoubtedly the most important transcriptional modulator of adipocyte development in all types of adipose tissue, members of the CCAAT/enhancer-binding protein, Krüppel-like transcription factor, signal transducer and activator of transcription, GATA, early B cell factor, and interferon-regulatory factor families also regulate adipogenesis. The importance of PPARγ activity is underscored by several covalent modifications that modulate its activity and its ability to modulate adipocyte development. This review will primarily focus on the transcriptional control of adipogenesis in white fat cells and on the mechanisms involved in this fine-tuned developmental process. © 2017 American Physiological Society. Compr Physiol 7:635-674, 2017.

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X‐box binding protein 1 enhances adipogenic differentiation of 3T3‐L1 cells through the downregulation of Wnt10b expression

Cited by 19 publications

References 26 publications

X‐box binding protein 1 is a novel key regulator of peroxisome proliferator‐activated receptor γ2

X‐box binding protein 1 is a novel key regulator of peroxisome proliferator‐activated receptor γ2

Adipocyte Spliced Form of X-Box–Binding Protein 1 Promotes Adiponectin Multimerization and Systemic Glucose Homeostasis

Transcriptional Regulation of Adipogenesis

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