ReprObesity · Overweight-induced Hypogonadism as major factor for the generation and/or perpetuation of Metabolic Co-morbidities of Obesity: Contribution of Epigenetic Regulatory Mechanisms
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-10-01 → 2018-09-30
- EU contribution
- €158,122
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
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Results in brief
Overweight-induced Hypogonadism as major factor for the generation and/or perpetuation of Metabolic Co-morbidities of Obesity: Contribution of Epigenetic Regulatory Mechanisms
Obesity has become one of the major health issues in the EU and worldwide. This complex medical condition is frequently linked to serious metabolic complications and deregulation of hormonal axes. Interestingly, different studies have suggested a potential link between obesity and hypogonadism, a reproductive disorder that might also promote metabolic alterations, thus setting a vicious circle in the generation and perpetuation of obesity co-morbidities. While the targets and molecular mechanisms underlying this phenomenon are still unknown, emerging evidence suggests the potential role of (i) the hypothalamic Kiss1/NKB neurons, which are deregulated in experimental models of metabolic stress linked to reproductive dysfunction, and (ii) epigenetic regulatory mechanisms, which have been shown to modulate the hypothalamic expression of Kiss1 under physiological conditions. In the above context, this project aimed to elucidate the pathophysiological relevance of epigenetic regulatory mechanisms in obesity-induced hypogonadism and its impact on the control of hypothalamic Kiss1/NKB neurons and the generation and maintenance of the metabolic complications of overweight. To this end, we have characterized the time-course of alterations of key hormonal and epigenetic factors in preclinical models of obesity and we have evaluated the contribution of epigenetic modifications in deregulation of hypothalamic Kiss1/NKB neurons in conditions of overweight. This project has allowed identifying specific molecular targets and epigenetic mechanisms responsible for the metabolic perturbations linked to obesity-induced hypogonadism, which will aid to define better tools for the treatment of these complications.
Data: CORDIS, © European Union
Project objective
Obesity is a global health problem whose prevalence is increasing substantially due to lifestyle changes. This complex medical condition is frequently linked to serious metabolic complications and deregulation of hormonal axes, which lead to perturbed homeostasis in conditions of overweight. Different studies have suggested that obesity is often associated to hypogonadism, a reproductive disorder that might also promote metabolic alterations, thus setting a vicious circle in the generation/perpetuation of obesity co-morbidities. While the targets and molecular mechanisms underlying this phenomenon are still unknown, emerging evidence from experimental models of metabolic stress linked to hypogonadism strongly suggests the potential role of perturbations of hypothalamic Kiss1/NKB neurons. Likewise, the recently identified involvement of epigenetics in the control of Kiss1 expression at puberty, a crucial stage in sexual development that is metabolically gated, suggests also the contribution of these regulatory mechanisms to this phenomenon. In this context, this project aims to elucidate the pathophysiological relevance of epigenetic regulatory mechanisms in obesity-induced hypogonadism and their influence in the generation/ maintenance of the metabolic complications of overweight. To this end, we will characterize the time-course of alterations of key hormonal and epigenetic factors in preclinical models of obesity and will evaluate the contribution of epigenetic modifications in deregulation of hypothalamic Kiss1/NKB neurons in conditions of overweight. In addition, we will analyse the potential role of gonadal steroids in this phenomenon. This project will help to identify the molecular targets and epigenetic mechanisms responsible for the metabolic perturbations linked to obesity-induced hypogonadism, and will aid to define better tools for the treatment of these complications.
Original text from CORDIS.
Participants
- UNIVERSIDAD DE CORDOBA · CORDOBACoordinatorSpain
Links
Data: CORDIS, © European Union