Networking activity of nuclear receptors during development and in adult metabolic homeostasis

My group is interested in exploring metabolic homeostasis. For the last decade, we focus our questions and models on the nuclear receptor family of transcription factors, more particularly on PPARs which play a major role in metabolic homeostasis. We used genetically modified mice models and applied state of the art molecular and cellular approaches to address the mechanism of homeostasis perturbations.

The recent works made use of a newly developed model of PPARγ full deletion in mice. These mice are totally deprived of adipocytes, allowing to explore the systemic metabolic consequences. We have thus gained insights into the mechanisms underlying the pathogenesis of different metabolic disorders that accompanied type 2 diabetes, such as metabolic inflexibility, diabetic nephropathy and steato-hepatitis, for which few «in vivo» models are satisfactory.

This model also unravelled the important paracrine activities of the adipose tissue, particularly in the skin development and homeostasis, but also on bone homeostasis (see video) and haematopoiesis.

We now are moving towards the evaluation of the homeostasis at an integrated level, i.e. at system levels, rather than organ or single factor levels. One main project presently developed in the laboratory aims at identifying the very early events occurring in the adipose tissue, including epigenetic modifications, metabolic activity, and tissular inflammatory response that contribute to the systemic metabolic perturbations observed upon high fat diet exposure, as well as during aging. The combination of «omics», their co-analyses and integration, with the possibility of modelling, requires competences in and development of bioinformatic tools.

3D microCT reconstruction of the femurs, in 12 month-old females. These images highlight a dramatic trabecularization of the bone architecture in Pparg ^Δ/Δ mice, which extends along the shaft almost reaching the mid-diaphysis. Interestingly, cortical bone was found to be extremely porous at both the epiphysis and diaphysis.