PHD-OB-T2D · STUDY THE ROLE OF OXYGEN SENSORS PROLYL HYDROXYLASE DOMAIN (PHD) PROTEIN IN OBESITY AND TYPE II DIABETES
FP7 — People (Marie Curie Actions)
- Duration
- 2008-03-01 → 2010-02-28
- EU contribution
- €164,887
- Participants
- 1
- Scheme
- MC-IEF
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Results in brief
Study the role of oxygen sensors Prolyl Hydroxylase Domain (PHD) protein in obesity and type II diabetes
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 we 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. We also aimed on determination of how loss of PHD function would alter pancreatic ß-cell physiology and whether alterations in glucose and lipid homeostasis would reveal a potentially beneficial effect to utilise PHD inhibition as a pharmaceutical intervention to treat obesity and T2D.
Data: CORDIS, © European Union
Project objective
Various alterations of metabolism are a central characteristic of physiological disorders and diseases, including cancer, obesity, type 2 diabetes (T2D) and the metabolic syndrome (MS) and are as such a major burden on national budgets. Thus, there is an urgent need to further understand the various processes that determine the occurence of metabolic alterations, predominantly obesity and T2D and to develop strategies to provide therapeutic aid. Several intrinsic factors either predetermine or correlate with the occurence of obesity and the development of T2D and MS. Our laboratory has recently reported a yet unidentified role of the mammalian oxygen sensor PHD1 in the control of glucose homeostasis by phenotyping PHD1 knockout mice. In detail, loss of PHD1 lowers oxygen consumption in skeletal muscle by shifting glucose metabolism from oxidative to more anaerobic ATP production which impairs oxidative muscle performance in healthy conditions, but induces hypoxia tolerance and protects myofibers against lethal ischemia. In addition, novel findings suggest a correlation between PHD1 and intrinsic obesity and T2D related factors. To extend our studies on PHD specific metabolic alterations we will utilize several in the lab made transgenic PHD mice to address the followong issues (i) assess obesity and T2D related changes in lipid and glucose homeostasis in mice lacking each of the PHDs either constitutively or specifically in key metabolic tissues by comparing various metabolic parameters before and after administration of a high fat diet (ii) determine the consequences of loss of PHD function in pancreatic ß-cell physiology, insulin signalling and glucose tolerance using a mouse model of dietary induced diabetes and (iii) determine whether loss of PHD function might have any potential for pharmaceutical intervention by intercrossing our PHD deficient mouse strains with well established mouse models to study obesity and obesity related disorders such as T2D and MS.
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
Data: CORDIS, © European Union