PPARβ/δ ameliorates fructose-induced insulin resistance in adipocytes by preventing Nrf2 activation

We studied whether PPARβ/δ deficiency modifies the effects of high fructose intake (30% fructose in drinking water) on glucose tolerance and adipose tissue dysfunction, focusing on the CD36-dependent pathway that enhances adipose tissue inflammation and impairs insulin signaling. Fructose intake for 8weeks significantly increased body and liver weight, and hepatic triglyceride accumulation in PPARβ/δ-deficient mice but not in wild-type mice. Feeding PPARβ/δ-deficient mice with fructose exacerbated glucose intolerance and led to macrophage infiltration, inflammation, enhanced mRNA and protein levels of CD36, and activation of the JNK pathway in white adipose tissue compared to those of water-fed PPARβ/δ-deficient mice. Cultured adipocytes exposed to fructose also exhibited increased CD36 protein levels and this increase was prevented by the PPARβ/δ activator GW501516. Interestingly, the levels of the nuclear factor E2-related factor 2 (Nrf2), a transcription factor reported to up-regulate Cd36 expression and to impair insulin signaling, were increased in fructose-exposed adipocytes whereas co-incubation with GW501516 abolished this increase. In agreement with Nrf2 playing a role in the fructose-induced CD36 protein level increases, the Nrf2 inhibitor trigonelline prevented the increase and the reduction in insulin-stimulated AKT phosphorylation caused by fructose in adipocytes. Protein levels of the well-known Nrf2 target gene NAD(P)H: quinone oxidoreductase 1 (Nqo1) were increased in water-fed PPARβ/δ-null mice, suggesting that PPARβ/δ deficiency increases Nrf2 activity; and this increase was exacerbated in fructose-fed PPARβ/δ-deficient mice. These findings indicate that the combination of high fructose intake and PPARβ/δ deficiency increases CD36 protein levels via Nrf2, a process that promotes chronic inflammation and insulin resistance in adipose tissue.

The merchant

L'objectiu d'aquest document és descriure el joc The Merchant, tant des del punt de vista tècnic com funcional, així com proporcionar el seu manual d'usuari. Es tracta d'un joc multi jugador, ambientat a l'espai, que té com a objectiu comerciar amb productes entre planetes.

Décrire une activité verbale et proposer une norme pour enseigner un savoir-faire : l'exemple d'un manuel de storytelling

This paper describes and analyses language norms in a storytelling manual published in the Frenchspeaking part of Switzerland. In the manual, storytelling is conceived as a means of persuasion and thus it appears that an appropriate storytelling should lead to believe or to act. What exactly is "appropriateness" in this specific case? In order to examine this issue, this paper addresses three questions: how storytelling is promoted as an efficient communicative technique; which methods are used to propose and support language norms (by showing "what the storyteller should do" and by saying "how he should do so"); and which are the criteria which define an appropriate story (semantic/formal and functional criteria) and an appropriate telling of the story (communicative and linguistic criteria).

The Interplay between NF-kappaB and E2F1 Coordinately Regulates Inflammation and Metabolism in Human Cardiac Cells

Pyruvate dehydrogenase kinase 4 (PDK4) inhibition by nuclear factor-κB (NF-κB) is related to a shift towards increased glycolysis during cardiac pathological processes such as cardiac hypertrophy and heart failure. The transcription factors estrogen-related receptor-α (ERRα) and peroxisome proliferator-activated receptor (PPAR) regulate PDK4 expression through the potent transcriptional coactivator PPARγ coactivator-1α (PGC-1α). NF-κB activation in AC16 cardiac cells inhibit ERRα and PPARβ/δ transcriptional activity, resulting in reduced PGC-1α and PDK4 expression, and an enhanced glucose oxidation rate. However, addition of the NF-κB inhibitor parthenolide to these cells prevents the downregulation of PDK4 expression but not ERRα and PPARβ/δ DNA binding activity, thus suggesting that additional transcription factors are regulating PDK4. Interestingly, a recent study has demonstrated that the transcription factor E2F1, which is crucial for cell cycle control, may regulate PDK4 expression. Given that NF-κB may antagonize the transcriptional activity of E2F1 in cardiac myocytes, we sought to study whether inflammatory processes driven by NF-κB can downregulate PDK4 expression in human cardiac AC16 cells through E2F1 inhibition. Protein coimmunoprecipitation indicated that PDK4 downregulation entailed enhanced physical interaction between the p65 subunit of NF-κB and E2F1. Chromatin immunoprecipitation analyses demonstrated that p65 translocation into the nucleus prevented the recruitment of E2F1 to the PDK4 promoter and its subsequent E2F1-dependent gene transcription. Interestingly, the NF-κB inhibitor parthenolide prevented the inhibition of E2F1, while E2F1 overexpression reduced interleukin expression in stimulated cardiac cells. Based on these findings, we propose that NF-κB acts as a molecular switch that regulates E2F1-dependent PDK4 gene transcription.

Annuaire des postes, ou Manuel du service de la poste aux lettres : à l'usage du commerce et des voyageurs / publié par ordre de l'administration

1843.

Annuaire des postes, ou Manuel du service de la poste aux lettres : à l'usage du commerce et des voyageurs / publié par ordre de l'administration

1901.

Annuaire du Cosmos : manuel de la science

1870 (A12).

Annuaire du Cosmos : manuel de la science

1864 (A6).

Annuaire du Cosmos : manuel de la science

1867 (A9).

Annuaire du Cosmos : manuel de la science

1862 (A4).

Annuaire du Cosmos : manuel de la science

1866 (A8).

Annuaire du Cosmos : manuel de la science

1869 (A11).