AM-879, a PPARy non-agonist and Ser273 phosphorylation blocker, promotes insulin sensitivity without adverse effects in mice

Obesity is one of the main risk factors for type 2 diabetes, and peroxisome proliferator-activated receptor γ (PPARγ) is considered a promising pathway on insulin sensitivity and adipose tissue metabolism. The search for molecules acting as insulin sensitizers have increased, especially for molecules that block PPARγ-Ser273 phosphorylation, without reaching full agonism. We evaluated the in vivo effects of AM-879, a PPARγ non-agonist, and found that AM-879 exerts different effects in mice depending on the dose. At lower doses, this ligand decreased BAT, increased leptin and Crh expression. However, at a higher dose, it promoted improvement on insulin sensitivity, ameliorates expression of metabolism-related genes, decreased the expression of genes related to liver toxicity, maintaining body weight and adipocyte size. These results present a new lead molecule to ameliorates insulin resistance and confirm AM-879 as a PPARγ non-agonist which blocks Ser273 phosphorylation as a good strategy to modulate insulin sensitivity without developing the adverse effects promoted by PPARγ full agonists

Euclid. I. Overview of the Euclid mission

The current standard model of cosmology successfully describes a variety of measurements, but the nature of its main ingredients, dark matter and dark energy, remains unknown. Euclid is a medium-class mission in the Cosmic Vision 2015-2025 programme of the European Space Agency (ESA) that will provide high-resolution optical imaging, as well as near-infrared imaging and spectroscopy, over about 14,000 deg^2 of extragalactic sky. In addition to accurate weak lensing and clustering measurements that probe structure formation over half of the age of the Universe, its primary probes for cosmology, these exquisite data will enable a wide range of science. This paper provides a high-level overview of the mission, summarising the survey characteristics, the various data-processing steps, and data products. We also highlight the main science objectives and expected performance

Euclid. I. Overview of the Euclid mission

International audienceThe current standard model of cosmology successfully describes a variety of measurements, but the nature of its main ingredients, dark matter and dark energy, remains unknown. Euclid is a medium-class mission in the Cosmic Vision 2015-2025 programme of the European Space Agency (ESA) that will provide high-resolution optical imaging, as well as near-infrared imaging and spectroscopy, over about 14,000 deg^2 of extragalactic sky. In addition to accurate weak lensing and clustering measurements that probe structure formation over half of the age of the Universe, its primary probes for cosmology, these exquisite data will enable a wide range of science. This paper provides a high-level overview of the mission, summarising the survey characteristics, the various data-processing steps, and data products. We also highlight the main science objectives and expected performance