Insulin and Sterol-regulatory Element-binding Protein-1c (SREBP-1C) Regulation of Gene Expression in 3T3-L1 Adipocytes

Lay, Soazig Le; Lefrère, Isabelle; Trautwein, Christian; Dugail, Isabelle; Krief, Stéphane

doi:10.1074/jbc.m203913200

Cited by 150 publications

(108 citation statements)

References 57 publications

(39 reference statements)

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“…We next performed experiments to assess the specificity of the apoE gene response to ciglitazone. Insulin is an important regulator of adipocyte gene expression (35). PPAR␣ is poorly expressed in adipocytes; however, PPAR␣ agonists have been reported to modulate adipocyte gene expression (36).…”

Section: Resultsmentioning

confidence: 99%

Divergent Effects of Peroxisome Proliferator-activated Receptor γ Agonists and Tumor Necrosis Factor α on Adipocyte ApoE Expression

Yue

Rasouli

Ranganathan

et al. 2004

Journal of Biological Chemistry

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ApoE is expressed in multiple mammalian cell types in which it supports cellular differentiated function. In this report we demonstrate that apoE expression in adipocytes is regulated by factors involved in modulating systemic insulin sensitivity. Systemic treatment with pioglitazone increased systemic insulin sensitivity and increased apoE mRNA levels in adipose tissue by 2-3-fold. Treatment of cultured 3T3-L1 adipocytes with ciglitazone increased apoE mRNA levels by 2-4-fold in a dose-dependent manner and increased apoE secretion from cells. Conversely, treatment of adipocytes with tumor necrosis factor (TNF) ␣ reduced apoE mRNA levels and apoE secretion by 60%. Neither insulin nor a peroxisome proliferator-activated receptor (PPAR) ␣ agonist regulated adipocyte apoE gene expression. In addition, treatment of human monocyte-derived macrophages with ciglitazone did not regulate expression of apoE. Additional analyses using reporter genes indicated that the effect of TNF␣ and PPAR␥ agonists on the apoE gene was mediated via distinct gene control elements. The TNF␣ effect was mediated by elements within the proximal promoter, whereas the PPAR␥ effect was mediated by elements within a downstream enhancer. However, the addition of TNF␣ substantially reduced the absolute levels of apoE reporter gene response even in the presence of ciglitazone. These results indicate for the first time that adipose tissue expression of apoE is modulated by physiologic regulators of insulin sensitivity.

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Section: Resultsmentioning

confidence: 99%

Divergent Effects of Peroxisome Proliferator-activated Receptor γ Agonists and Tumor Necrosis Factor α on Adipocyte ApoE Expression

Yue

Rasouli

Ranganathan

et al. 2004

Journal of Biological Chemistry

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“…Many groups have established that insulin upregulates SREBP1c mRNA and mature SREBP1 protein and is accompanied by increases in FA biosynthetic gene expression. [33][34][35] As the product of the ACC-catalysed reaction, there is also an increase in the levels of malonyl-CoA, leading to the inhibition of CPT1 and mitochondrial FA oxidation (Figure 3). Work in our lab has shown that in human WAT, the majority of SREBP1 expressed is in the SREBP1c isoform.…”

Section: Srebp1c a Gatekeeper For Lipotoxicitymentioning

confidence: 99%

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

2004

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Obesity and type 2 diabetes mellitus are the major noncommunicable public health problem of the 21st century. The best strategy to tackle this problem is to develop strategies to prevent/treat obesity. However, it is becoming clear that despite successful research identifying weight regulatory pathways, the development of the obesity epidemic is outpacing scientific progress. The lack of success controlling the obesity epidemic in an aging population will result in another subsequent uncontrolled epidemic of complications. Our research focuses on the mechanisms causing lipotoxicity aiming to identify suitable strategies to prevent or at least retard the development of the metabolic syndrome. Previous work using transgenic and knockout mouse models has shown an interplay between white adipose tissue and skeletal muscle linking fatty acid (FA) synthesis with reciprocal effects on FA oxidation. Work from our lab and others suggests that defective adipose tissue is a key link between obesity, insulin resistance and type 2 diabetes mellitus by promoting the development of lipotoxicity in peripheral tissues. We propose a series of models to describe the process by which the adipose tissue could react to an energy-rich environment and responds depending on genetic and physiological factors, impacting on the functions of other peripheral tissues. We suggest that by examining hypotheses that encompass multiple organs and the partitioning of energy between these organs, a suitable strategy can be devised for the treatment of chronic obesity.

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“…We next assessed the expression of fatty acid synthase and stearoyl-CoA desaturase 1, because insulin regulates fatty acid synthesis by regulating the expression of these genes, via sterol regulatory element binding protein-1C (32,33). With the exception of fatty acid synthase in the TNF model and stearoyl-CoA desaturase 1 in the DEX and TNF models, the levels of these proteins were unaffected by insulin resistance (Fig.…”

Section: Insulin Resistance Is Confined To Glucose Metabolism Inmentioning

confidence: 99%

Selective Insulin Resistance in Adipocytes

Tan

Fisher‐Wellman

Fazakerley³

et al. 2015

Journal of Biological Chemistry

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Background: Insulin resistance is an early risk factor for metabolic disease. Results: Using various insulin resistance models, insulin regulation of glucose metabolism was universally blunted, whereas other actions (protein synthesis and anti-lipolysis) were unimpaired. Conclusion: Insulin resistance is selective for glucose metabolism in adipocytes. Significance: Chronic hyperactivation of unaffected insulin action pathways in the context of the metabolic syndrome likely contributes to disease progression.

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Insulin and Sterol-regulatory Element-binding Protein-1c (SREBP-1C) Regulation of Gene Expression in 3T3-L1 Adipocytes

Cited by 150 publications

References 57 publications

Divergent Effects of Peroxisome Proliferator-activated Receptor γ Agonists and Tumor Necrosis Factor α on Adipocyte ApoE Expression

Divergent Effects of Peroxisome Proliferator-activated Receptor γ Agonists and Tumor Necrosis Factor α on Adipocyte ApoE Expression

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

Selective Insulin Resistance in Adipocytes

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