Protein kinase A suppresses the differentiation of 3T3-L1 preadipocytes

Li, Fuqiang; Wang, Dongmei; Zhou, Yiran; Zhou, Bo; Yang, Yaran; Chen, Hehua; Song, Jianguo

doi:10.1038/cr.2008.12

Cited by 57 publications

(48 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that human adipose tissue exhibits important BMI-related differences in the expression and activity of PRKAR2B that might contribute to the variability of cAMP-stimulated lipolysis in obese and nonobese subjects (12). However, data on the expression and function of the different PKA regulatory subunits during adipose tissue differentiation are few and contradictory (14,15). Moreover, these studies have been carried out in murine cell line models, mainly 3T3-L1 preadipocytes, while studies in human models of adipocyte differentiation are still scarce.…”

Section: Introductionmentioning

confidence: 95%

PKA regulatory subunit R2B is required for murine and human adipocyte differentiation

Peverelli¹,

Ermetici²,

Corbetta³

et al. 2014

EJEA

View full text Add to dashboard Cite

Adipogenesis is a complex process modulated by several factors, including cAMP signaling. The main cAMP target is protein kinase A (PKA), a tetrameric enzyme with four regulatory subunits showing tissue-specific expression and function: PRKAR2B is the main regulatory subunit in adipose tissue in mice and in adult humans. This study aimed to evaluate the expression of PKA regulatory subunits in human adipose tissue during fetal development and to investigate their role in the differentiation of 3T3-L1 and primary human preadipocytes. The expression of PKA regulatory subunits was evaluated in fetal adipose tissue (immunohistochemistry) and in cultured 3T3-L1 and primary human preadipocytes (western blot analysis). Cultured cells were transiently transfected with siRNA against PRKAR2B and induced to differentiate. Differentiation was evaluated by intracellular triglyceride staining (Oil Red O) and expression of molecular markers of adipocyte differentiation. In this study, we found that PRKAR2B is the main regulatory subunit in human adipose tissue during fetal development, from 12 weeks of gestation to the end of gestation, as well as in 3T3-L1 and primary human preadipocytes. The expression of PRKAR2B increases progressively during in vitro differentiation. The silencing of PRKAR2B abolishes the increase in the expression of peroxisome proliferator-activated receptor gamma (PPARg (PPARG)), fatty acid synthase, aP2 (FABP4), and lipoprotein lipase, as well as intracellular triglyceride accumulation, resulting in impaired adipocyte differentiation in both mouse and human cell systems. In conclusion, PRKAR2B is the key PKA regulatory subunit involved in mouse and human adipose tissue development. The physiological increase in the expression of PRKAR2B is an essential event in adipogenesis in both mice and humans, and it might represent a possible target for future strategies for obesity treatment.

show abstract

Section: Introductionmentioning

confidence: 95%

PKA regulatory subunit R2B is required for murine and human adipocyte differentiation

Peverelli¹,

Ermetici²,

Corbetta³

et al. 2014

EJEA

View full text Add to dashboard Cite

show abstract

“…During the early differentiation of preadipocytes, inhibition of ERK and activation of the AMP-activated protein kinase (AMPK) and cAMP/protein kinase A (PKA) signaling pathways inhibit PPAR ␥ , C/EBP ␣ , and SREBP1c activation and adipocyte differentiation (39)(40)(41). Previous studies have demonstrated that promoting the effects of EETs attenuates ERK1/2 dephosphorylation in endothelial cells, activates AMPK activity in liver, and activates the cAMP/PKA pathway in the vascular system ( 12,42,43 ), suggesting that a complex interaction between CYP-derived EETs and multiple signaling pathways also likely exist in the early phase of adipogenesis.…”

Section: Downloaded Frommentioning

confidence: 99%

Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity

Zha

Edin

Vendrov

et al. 2014

Journal of Lipid Research

View full text Add to dashboard Cite

Obesity is a major public health problem that contributes to the development of type 2 diabetes and cardiovascular disease ( 1 ). Excessive lipid accumulation in adipose tissue is a key pathological driver of obesity, and is manifested by an increase in the number (hyperplasia) and size (hypertrophy) of adipocytes. Differentiation of preadipocytes to mature adipocytes (adipogenesis) is an integral mediator of this process, and is under the control of a transcription factor network that regulates lipid biosynthesis and metabolism ( 2 ). Most notably, PPAR-␥ , CCAAT/ enhancer-binding protein (C/EBP) ␣ , and sterol regulatoryelement-binding protein (SREBP)1c are central mediators of this process through the regulation of LPL, acetyl-CoA carboxylase 1 (ACC1), and FAS expression ( 2, 3 ). Sustained activation of this process, however, is a key pathological driver of obesity that results in adipocyte dysfunction, glucose intolerance, and ultimately the development of insulin resistance and type 2 diabetes ( 4, 5 ). Consequently, an improved understanding of the key pathways that regulate adipogenesis and adipocyte function offers enormous potential to facilitate the development of novel therapeutic strategies that mitigate the development and progression of obesity-associated metabolic diseases. Abstract

show abstract

“…Overexpression of RhoA resulted in osteogenic differentiation, whereas expression of dominant negative RhoA lead to the formation of adipocytes in the absence of any inducing factors. In addition to these findings, Li et al demonstrated that, although both forskolin and 8-brcAMP enhance dexamethasone-, insulin-stimulated adipogenesis, but in the presence of the phosphodiesterase MIX, these compounds inhibited adipogenic differentiation [49]. Most likely, the increased cAMP levels are rapidly decreased in the absence of MIX, whereas in the absence, a prolonged continuous rise in cAMP levels occurs.…”

Section: Discussionmentioning

confidence: 94%

Diverse Effects of Cyclic AMP Variants on Osteogenic and Adipogenic Differentiation of Human Mesenchymal Stromal Cells

Doorn

Leusink

Gröen

et al. 2012

Tissue Engineering Part A

View full text Add to dashboard Cite

Osteogenic differentiation of human mesenchymal stromal cells (hMSCs) may potentially be used in cell based bone tissue engineering applications to enhance the bone forming potential of these cells. Osteogenic and adipogenic differentiation are thought to be mutually exclusive and, although several signaling pathways and cues that induce osteogenic or adipogenic differentiation respectively have been identified, there is no general consensus on how to optimally differentiate hMSCs into the osteogenic lineage. Some pathways have also been reported to be involved in both adipogenic and osteogenic differentiation, as for example the protein kinase A (PKA) pathway, and the aim of this study was to investigate the role of cAMP / PKA signaling in differentiation of hMSCs in more detail. We show that activation of this pathway with dibutyryl-cAMP results in enhanced alkaline phosphatase expression whereas another cAMP analogue induces adipogenesis in long-term mineralization cultures. Adipogenic differentiation, induced by 8-bromo-cAMP, was accompanied by stronger PKA activity and higher expression of cAMP-responsive genes, suggesting that stronger activation correlates with adipogenic differentiation. In addition, whole genome expression analysis showed an increase in expression of adipogenic genes in 8-br-cAMP-treated cells. Furthermore, by means of qPCR, we show differences in peroxisome proliferator activated receptor-γ (PPARγ) activation, either alone, or in combination with dexamethasone, thus demonstrating differential effects of the PKA pathway, most likely depending on its mode of activation.

show abstract

Protein kinase A suppresses the differentiation of 3T3-L1 preadipocytes

Cited by 57 publications

References 49 publications

PKA regulatory subunit R2B is required for murine and human adipocyte differentiation

PKA regulatory subunit R2B is required for murine and human adipocyte differentiation

Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity

Diverse Effects of Cyclic AMP Variants on Osteogenic and Adipogenic Differentiation of Human Mesenchymal Stromal Cells

Contact Info

Product

Resources

About