Project description
Can obesity affect puberty?
Accumulating evidence suggests that obesity is linked to disturbed puberty. Obesity is largely a hypothalamic disease, while neuronal networks in the hypothalamus also regulate puberty. Funded by the European Research Council, the DOPA-Kiss project aims to uncover the impact of obesity on puberty by integrating omics data and studying metabolic sensing in Kiss1 neurons in the hypothalamus. Project objectives include the investigation of the metabolic control of puberty alongside the identification of pathophysiological processes related to obesity. Given the high prevalence of obesity in adolescence, project findings will pave the way for novel interventions against obesity-induced puberty changes.
Objective
Child obesity is a worrying condition, affecting 20% adolescents. Among its comorbidities, early obesity is linked to disturbed puberty, which is more evident in girls, but bound to adverse health outcomes in both sexes. Yet, how our brain decodes nutritional info to finely control puberty remains unsolved. Genetic data suggest obesity is largely an hypothalamic disease. Puberty is also hypothalamic-driven and governed by complex neuronal circuits. Among them, Kiss1 neurons have emerged as key elements in the brain control of puberty and its metabolic regulation, likely in cooperation with other central signaling systems, as POMC/melanocortins. Yet, the mechanisms whereby early obesity impacts on different Kiss1 neuronal populations and pubertal timing are ill-defined. The global aim of DOPA-Kiss is to unveil the brain basis of obesity-induced pubertal alterations in both sexes, with a major focus on Kiss1 neurons. An integral research plan will be implemented based on (i) Multidimensional integration of omics data, including hypothalamic global and spatial metabolomics, as well as transcriptomic and epigenomic profiling of Kiss1 neuronal subpopulations during pubertal maturation in conditions of obesity; (ii) Analysis of the molecular mechanisms for nutrient & metabolic sensing at the hypothalamus, and particularly in Kiss1 neurons; and (iii) Functional genomic dissection of key metabolic pathways in Kiss1 neurons using Cre/LoxP- & CRISPR-based genome editing in vivo. Sex differences in the impact of early obesity on subsets of Kiss1 neurons and puberty, and, when relevant, parallel changes in POMC neurons, will be explored. Putative human correlates of our experimental data will be scrutinized using public databases. DOPA-Kiss will not only surface unsolved aspects of the metabolic control of puberty, but will reveal also groundbreaking info on pathophysiological mechanisms and putative targets of intervention in conditions of altered puberty due to early obesity.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
14005 CORDOBA
Spain
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