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 nuclear factor kB (NF-kB)/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.
Highlights d Midgut NF-kB/Relish function modulates dietary adaptation of microbiota d NF-kB/Relish limits the diet inducibility of 4E-BP/Thor d 4E-BP/Thor dictates diet-dependent changes in microbiota composition d Cap-dependent translation is required for dietary adaptation of microbiota
A hands-on activity appropriate for first-semester general chemistry students is presented that combines traditional VSEPR methods of predicting molecular geometries with introductory use of molecular modeling. Students analyze a series of previously calculated output files consisting of several molecules each in various geometries. Each structure is analyzed with respect to the calculated relative energies and bond angles and then compared to the predicted geometry obtained using VSEPR theory. Therefore, students gain exposure to and an introductory experience in computational chemistry, while reinforcing the connection between VSEPR theory and "pseudoexperimental" results obtained from the calculations. This exercise can be completed by first-semester general chemistry students in a 3-h time period and without the need for students to learn how to actually perform the calculation themselves. The benefits of the exercise as well as the impact of such visualization activities on spatial orientation, particularly with respect to gender, are discussed.
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