Role of Inhibitor of Kappa B Kinase Epsilon in Sex-dependent Differences in Metaflammation (360G-Wellcome-206453_Z_17_Z)

£589,119

With the failure in curbing the global obesity epidemic, there is an urgent need to develop therapies to treat obesity-associated metabolic diseases. This requires a better understanding of the molecular mechanisms that not only promote, but also prevent metabolic disease development. Although, chronic low-grade inflammation ("metaflammation") is an important causative factor in metabolic diseases, the anti-inflammatory effects of estrogens may provide important insights into disease prevention. Indeed, pre-menopausal women are protected from obesity-linked metabolic diseases. Previously, I have identified immunometabolic proteins, e.g. IKBKE, that limit metabolic stress-induced inflammation and these are influenced by sex. However, it remains unclear whether, and how, estrogens alter innate immune sensitivity to metabolic stress. This project will address this and test the hypothesis that both estrogen- and IKBKE-dependent pathways function in a common signalling network to regulate energy balance and metaflammation. I will investigate, invitro and invivo, the synergies that exist between estrogen- and IKBKE-depended actions in metaflammation. Ultimately, the knowledge gained may support the notion that estrogens and IKBKE are key in raising the threshold for metabolic stress-induced inflammation. This may identify novel therapeutic targets to treat obesity-linked metabolic diseases and shed light on the immunometabolic changes that accompany menopause in all ageing women.

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Grant Details

Amount Awarded 589119
Applicant Surname Sethi
Approval Committee Basic Science Interview Committee
Award Date 2017-04-19T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Career Re-Entry Fellowship
Internal ID 206453/Z/17/Z
Lead Applicant Prof Jaswinder Sethi
Partnership Value 589119
Planned Dates: End Date 2023-03-09T00:00:00+00:00
Planned Dates: Start Date 2017-09-10T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
Sponsor(s) Prof Isabel Temple