The Extracellular Signal–Regulated Kinase Isoform ERK1 Is Specifically Required for In Vitro and In Vivo Adipogenesis

Bost, Fréd́eric; Aouadi, Myriam; Caron, Leslie; Even, Patrick C.; Belmonte, Nathalie; Prot, Matthieu; Dani, Christian; Hofman, Paul; Pagès, Gilles; Pouysségur, Jacques; Marchand-Brustel, Y. Le; Binétruy, Bernard

doi:10.2337/diabetes.54.2.402

Cited by 292 publications

(243 citation statements)

References 35 publications

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“…ERK1-null mice are viable and fertile; however, thymocyte maturation is impaired in these mice (Pages et al, 1999). Other studies also show that ERK1-null mice have increased locomotor activity (Mazzucchelli et al, 2002) and impaired adipocyte differentiation (Bost et al, 2005). In contrast, ERK2-null mice show completely different phenotypes; these mice die at embryonic day 6.5-8.5 due to impaired mesoderm differentiation and placental development (Hatano et al, 2003;Saba-El-Leil et al, 2003;Yao et al, 2003).…”

Section: Mapk Signaling Erk1/2mentioning

confidence: 99%

MAPK signaling in inflammation-associated cancer development

2010

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Mitogen-activated protein (MAP) kinases comprise a family of protein-serine/threonine kinases, which are highly conserved in protein structures from unicellular eukaryotic organisms to multicellular organisms, including mammals. These kinases, including ERKs, JNKs and p38s, are regulated by a phosphorelay cascade, with a prototype of three protein kinases that sequentially phosphorylate one another. MAPKs transduce extracellular signals into a variety of cellular processes, such as cell proliferation, survival, death, and differentiation. Consistent with their essential cellular functions, MAPKs have been shown to play critical roles in embryonic development, adult tissue homeostasis and various pathologies. In this review, we discuss recent findings that reveal the profound impact of these pathways on chronic inflammation and, particularly, inflammation-associated cancer development.

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Section: Mapk Signaling Erk1/2mentioning

confidence: 99%

MAPK signaling in inflammation-associated cancer development

2010

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“…However, unlike Erk1 −/− mice, Erk2 −/− mice are not viable, suggesting that these kinases have non-redundant functions [15][16][17]. We have previously reported that ERK1 rather than ERK2 was involved in adipocyte differentiation and in adipogenesis in vivo [18,19]. Indeed, Erk1 −/− mice have reduced fat content and remain lean when exposed to a high-fat diet.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, Erk1 −/− mice have reduced fat content and remain lean when exposed to a high-fat diet. The leanness of the mice on a high-fat diet could be explained, at least in part, by the reduced adipogenesis, but these mice also have an increase in their postprandial metabolic rate that could contribute to the observed phenotype [18]. Erk1 −/− mice are also protected against insulin resistance when exposed to a high-fat diet [18].…”

Section: Introductionmentioning

confidence: 99%

Deficiency in the extracellular signal-regulated kinase 1 (ERK1) protects leptin-deficient mice from insulin resistance without affecting obesity

et al. 2010

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Aims/hypothesis Extracellular signal-regulated kinase (ERK) activity is increased in adipose tissue in obesity and type 2 diabetes mellitus and strong evidences suggests that it is implicated in the downregulation of insulin signalling and action in the insulin-resistant state. To determine the role of ERK1 in obesity-associated insulin resistance in vivo, we inactivated Erk1 (also known as Mapk3) in obese leptindeficient mice (ob/ob).Methods Mice of genotype ob/ob-Erk1 −/− were obtained by crossing Erk1 −/− mice with ob/ob mice. Glucose tolerance and insulin sensitivity were studied in 12-week-old mice. Tissue-specific insulin sensitivity, insulin signalling, liver steatosis and adipose tissue inflammation were determined. Results While ob/ob-Erk1 −/− and ob/ob mice exhibited comparable body weight and adiposity, ob/ob-Erk1 −/− mice did not develop hyperglycaemia and their glucose tolerance was improved. Hyperinsulinaemic-euglycaemic clamp studies demonstrated an increase in whole-body insulin sensitivity in the ob/ob-Erk1 −/− mice associated with an increase in both insulin-stimulated glucose disposal in skeletal muscles and adipose tissue insulin sensitivity. This occurred in parallel with improved insulin signalling in both tissues. The ob/ob-Erk1 −/− mice were also partially protected against hepatic steatosis with a strong reduction in acetyl-CoA carboxylase level. These metabolic improvements were associated with reduced expression of mRNA encoding inflammatory cytokine and T lymphocyte markers in the adipose tissue. Conclusions/interpretation Our results demonstrate that the targeting of ERK1 could partially protect obese mice against insulin resistance and liver steatosis by decreasing adipose tissue inflammation and by increasing muscle glucose uptake. Our results indicate that deregulation of the ERK1 pathway could be an important component in obesity-associated metabolic disorders.

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“…Upon activation, mTORC1 promotes protein translation and cell growth via regulation of the downstream eukaryotic translation initiation factor 4E (eIF4E) and the eIF4E-binding protein 1 (4E-BP1) [10]. Upstream regulators of mTORC1 includes AKT [11], AMPK [12] and MAP-kinase-extracellular regulated kinase (ERK) [13].…”

Section: Introductionmentioning

confidence: 99%

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)

Hagland

Nilsson

Burri

et al. 2013

Biochemical and Biophysical Research Communications

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Word count: 4587 2 ABSTRACTThe hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins.Transcription analysis further confirmed activation of PPARα-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR targets eIF4G and 4E-BP1 were induced. In summary, TTA increases hepatocyte respiration by inducing hypertrophy and mitochondrial biogenesis in rat, via adaptive regulation of PPARs as well as mTOR.

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The Extracellular Signal–Regulated Kinase Isoform ERK1 Is Specifically Required for In Vitro and In Vivo Adipogenesis

Cited by 292 publications

References 35 publications

MAPK signaling in inflammation-associated cancer development

MAPK signaling in inflammation-associated cancer development

Deficiency in the extracellular signal-regulated kinase 1 (ERK1) protects leptin-deficient mice from insulin resistance without affecting obesity

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)

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