The Epoxygenases CYP2J2 Activates the Nuclear Receptor PPARα In Vitro and In Vivo

Peroxisome proliferator-activated receptors (PPARs) are a family of three (PPARalpha, -beta/delta, and -gamma) nuclear receptors. In particular, PPARalpha is involved in regulation of fatty acid metabolism, cell growth and inflammation. PPARalpha mediates the cardiac fasting response, increasing fatty acid metabolism, decreasing glucose utilisation, and is the target for the fibrate lipid-lowering class of drugs. However, little is known regarding the endogenous generation of PPAR ligands. CYP2J2 is a lipid metabolising cytochrome P450, which produces anti-inflammatory mediators, and is considered the major epoxygenase in the human heart.Expression of CYP2J2 in vitro results in an activation of PPAR responses with a particular preference for PPARalpha. The CYP2J2 products 8,9- and 11-12-EET also activate PPARalpha. In vitro, PPARalpha activation by its selective ligand induces the PPARalpha target gene pyruvate dehydrogenase kinase (PDK)4 in cardiac tissue. In vivo, in cardiac-specific CYP2J2 transgenic mice, fasting selectively augments the expression of PDK4.Our results establish that CYP2J2 produces PPARalpha ligands in vitro and in vivo, and suggests that lipid metabolising CYPs are prime candidates for the integration of global lipid changes to transcriptional signalling events

Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease

This work was funded by the Diabetes Research and Wellness Fund. WA is in receipt of an MRC New Investigator Award

Effects of Ghrelin in the Heart

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Characteristics of patients recruited in prospective (London) cohort with periodontitis or no periodontitis.

<p>Characteristics of patients recruited in prospective (London) cohort with periodontitis or no periodontitis.</p

Spearman correlation of periodontitis with patient characteristics.

<p>Spearman correlation of periodontitis with patient characteristics.</p

Models for the association between indicators of periodontitis and steatosis (n = 8172).

<p>Models for the association between indicators of periodontitis and steatosis (n = 8172).</p

Characteristics of respondents in NHANES III with steatosis on ultrasound and low risk versus indeterminate / high risk scores by NAFLD fibrosis score (NFS, n = 2835).

<p>Characteristics of respondents in NHANES III with steatosis on ultrasound and low risk versus indeterminate / high risk scores by NAFLD fibrosis score (NFS, n = 2835).</p

Characteristics of patients recruited in prospective (London) cohort with periodontitis or no periodontitis.

<p>Characteristics of patients recruited in prospective (London) cohort with periodontitis or no periodontitis.</p

Development of an academic disease registry for spinal muscular atrophy

We report the development of a new disease registry on SMA as the result of a collaboration among three national networks in United States, Italy, and United Kingdom in partnership with a biotechnology company and with the support of advocacy groups.The aim of establishing a large collaborative registry within academic centers was to establish a structured but flexible system for collection of prospective, highly curated data that will deeply phenotype all patients with SMA and follow them longitudinally over several years.This paper describes the process leading to the development of the registry including the identification of the relevant data elements, the design of an electronic CRF with a shared data dictionary, the piloting of the first version and the definition of the final version.The registry will provide a central structure for conducting academic studies based on a much larger cohort of patients than those available in the individual networks. Due to the quality control of the data collected the registry can also be used for postmarketing purposes, allowing to share, in a transparent and controlled way, real-world data with pharmaceutical partners, drug regulatory agencies, and advocacy groups for better understanding of safety and effectiveness of new treatments. (C) 2019 Published by Elsevier B.V