Selective Phosphorylation of Akt/Protein-Kinase B Isoforms in Response to Dietary Cues

Abstract

A calorie-rich diet is one reason for the continuous spread of metabolic syndromes in western societies. Smart food design is one powerful tool to prevent metabolic stress, and the search for suitable bioactive additives is a continuous task. The nutrient-sensing insulin pathway is an evolutionary conserved mechanism that plays an important role in metabolism, growth and development. Recently, lipid cues capable to stimulate insulin signaling were identified. However, the mechanistic base of their activity remains obscure to date. We show that specific Akt/Protein-kinase B isoforms are responsive to different calorie-rich diets, and potentiate the activity of the cellular insulin cascade. Our data add a new dimension to existing models and position Drosophila as a powerful tool to study the relation between dietary lipid cues and the insulin-induced cellular signal pathway.

DIlp7-Producing Neurons Regulate Insulin-Producing Cells in Drosophila

“…In adult head samples, two AKT isoforms are detectable, and the phosphorylation state of the isoform AKT 85 is instructive for sugar uptake into cells (Trautenberg et al, 2019). Moreover, AKT possesses multiple phosphorylation sites and antibodies are in exsitance to detect phosphorylation at AKT Thr−342 and AKT Ser−505 (Trautenberg et al, 2019). We could not detect differences in the AKT 85−Thr342 phosphorylation state for any of the tested genotypes kept on CF (Supplementary Figure 3A).…”

“…To investigate if dIlp7 is involved in the regulation of the cellular IS cascade activity on yeast free diet, we quantified the phosphorylation state of AKT in different mutant backgrounds. In adult head samples, two AKT isoforms are detectable, and the phosphorylation state of the isoform AKT 85 is instructive for sugar uptake into cells (Trautenberg et al, 2019). Moreover, AKT possesses multiple phosphorylation sites and antibodies are in exsitance to detect phosphorylation at AKT Thr−342 and AKT Ser−505 (Trautenberg et al, 2019).…”

“…Sample preparation, western-blotting and quantification were performed as published by Trautenberg et al (2019). In brief, flies were raised on normal food and 5 days-old adults were transferred onto respective experimental foods for 7 days at 20 • C. Thereafter, flies were snap-frozen in liquid nitrogen and frozen heads from females collected for processing.…”

Diet and heat - one neuronal subset two responses

“…CF is rich in calories, its protein:sugar ratio is optimized and contains about 10% lipids ((39) and Table 1). Nevertheless, on CF, systemic Insulin levels are low and wild-type larvae struggle to complete their development (39,48). Astonishingly, we found that the absence of both dIlp2 and dIlp7 improved larval survival on CF up to numbers shown by controls.…”

“…AKT detection in yeast and corn-food fed adult heads Sample preparation, western-blotting and quantification were performed as published by (48). In brief, flies were raised on normal food and 5d old adults transferred onto respective experimental foods for 7d at 20°C.…”