Dr Nicolas Bonnet

Hjelt grant holder 2016, University of Geneva

PPARγ signaling in bone cells controls glucose homeostasis implications in diabetes and osteoporosis

Type 2 diabetes mellitus (T2DM) and osteoporosis are two major disorders which prevalence increases with aging and is predicted to worsen in the coming years. Preclinical investigations suggest common mechanisms implicated in the pathogenesis of both disorders. Recent evidence has established that there is a clear link between glucose and bone metabolism. The emergence of bone as an endocrine regulator has led to the re-evaluation of the role of bone cells in the development of metabolic diseases such as T2DM.

The grant generously provided by the Hjelt Foundation will be used to clarify how bone cell can contribute in the regulation of glucose homeostasis. We already provide evidence that in mice that lack the gene encoding the transcription factor PPARγ in specific bone cells (osteocytes, Ocy-Pparγ-/-) exhibit an increase in energy expenditure and an improvement in glucose homeostasis, in addition to a better bone strength.

This project aims to further elucidate the mechanisms by which PPARγ expression in bone cells regulates energy metabolism. First, we will investigate if under high fat diet Ocy-Pparγ-/- mice are protected against bone fragility, fat accumulation, steatotic livers and the development of insulin resistance all associated with obesity. Second, we will elucidate which insulin sensitizing bone derived hormone exerts these metabolic effects.

In the future, the group of Pr Ferrari, in which Dr Nicolas Bonnet is conducting this research, will try to identify other bone-derived factors able to regulate glycemia. As a proof of concept this research can be quickly validated in humans by investigating GERICO cohort currently composed of 1000 retired workers who have been followed up for more than 6 years with assessments of risk of incident diabetes according to insulin sensitizing bone derived hormone.

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