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Final Report - PHD-OB-T2D (Study the role of oxygen sensors Prolyl Hydroxylase Domain (PHD) protein in obesity and type II diabetes)

Project ID: 221684
Funded under: FP7-PEOPLE


Obesity is one of the most serious and fast-growing health problem in the European Union, and a leading cause of diabetes. In spite of the commercial and medical interest, there is a clear lack of new effective pharmaceutical treatments approved, and a limited clinical pipeline. The main barrier for approval of an anti-obesity drug is the safety requirements given the huge number of patients.

The central aim of the proposed project was to elucidate the potential of prolyl hydroxylases domain (PHD) protein inhibition as a means to interfere with the development of obesity and type 2 diabetes (T2D). To this end, the project induced obesity via high fat diet (HFD) feeding in PHD-deficient mice and monitored whether PHD deficiency would have consequences on weight gain and obesity-associated medical complications such as insulin resistance (IR) and glucose intolerance (GI), which would ultimately lead to the development of T2D.

In their report, the project partners conclude that inhibition of PHD1 might aggravate obesity associated disorders, such as T2D. Consequently, PHD inhibition might not serve as a potential means to treat these diseases, but clearly further studies are needed to provide a distinct answer to this question. Notably, hypoxia, leading to inactive PHDs, is also a hallmark of several diabetic complications, such as vascular dysfunction. The report includes three figures.

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