Details

Autor(en) / Beteiligte

• Molaei, Maral

Titel

Nf-ĸB/Relish and the Control of Cellular Triglyceride Metabolism in Drosophila Melanogaster

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2019

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Metabolic and innate immune signaling pathways have co-evolved to elicit coordinated responses. However, dissecting the integration of these ancient signaling mechanisms remains a challenge. Using Drosophila, we uncovered a role for the innate immune transcription factor NFκB/Relish in governing lipid metabolism during metabolic adaptation to fasting. We found that Relish is required to restrain fasting-induced lipolysis, and thus conserve cellular triglyceride levels during metabolic adaptation, through specific repression of ATGL/Brummer lipase gene expression in adipose (fat body). Fasting-induced changes in Brummer expression and, consequently, triglyceride metabolism are adjusted by Relish-dependent attenuation of FoxO transcriptional activation function, a critical metabolic transcription factor. Relish limits FoxO function by influencing fasting-dependent histone deacetylation and subsequent chromatin modifications within the Bmm locus. These results highlight that the antagonism of Relish and FoxO functions are crucial in the regulation of lipid metabolism during metabolic adaptation, which may further influence the coordination of innate immune-metabolic responses.