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. 2024 Aug 20;14(8):1037.
doi: 10.3390/biom14081037.

Glut1 Functions in Insulin-Producing Neurons to Regulate Lipid and Carbohydrate Storage in Drosophila

Matthew R Kauffman  1 , Justin R DiAngelo  1
Affiliations

Glut1 Functions in Insulin-Producing Neurons to Regulate Lipid and Carbohydrate Storage in Drosophila

Matthew R Kauffman et al. Biomolecules. .

Abstract

Obesity remains one of the largest health problems in the world, arising from the excess storage of triglycerides (TAGs). However, the full complement of genes that are important for regulating TAG storage is not known. The Glut1 gene encodes a Drosophila glucose transporter that has been identified as a potential obesity gene through genetic screening. Yet, the tissue-specific metabolic functions of Glut1 are not fully understood. Here, we characterized the role of Glut1 in the fly brain by decreasing neuronal Glut1 levels with RNAi and measuring glycogen and TAGs. Glut1RNAi flies had decreased TAG and glycogen levels, suggesting a nonautonomous role of Glut1 in the fly brain to regulate nutrient storage. A group of hormones that regulate metabolism and are expressed in the fly brain are Drosophila insulin-like peptides (Ilps) 2, 3, and 5. Interestingly, we observed blunted Ilp3 and Ilp5 expression in neuronal Glut1RNAi flies, suggesting Glut1 functions in insulin-producing neurons (IPCs) to regulate whole-organism TAG and glycogen storage. Consistent with this hypothesis, we also saw fewer TAGs and glycogens and decreased expression of Ilp3 and Ilp5 in flies with IPC-specific Glut1RNAi. Together, these data suggest Glut1 functions as a nutrient sensor in IPCs, controlling TAG and glycogen storage and regulating systemic energy homeostasis.

Keywords: Drosophila; Glut1; Ilp3; Ilp5; TAG; glycogen; neurons.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Inducing RNAi to the Glut1 gene in all neurons in Drosophila decreases whole-organism TAG and glycogen storage. (A) TAG and (B) glycogen normalized by protein content were measured in whole nSyb-Gal4>Glut1RNAi-TRiP (n = 34) and nSyb-Gal4>Glut1RNAi-VDRC (n = 30) flies and compared to nSyb-Gal4>LucRNAi (n = 29) and nSyb-Gal4>GFPRNAi (n = 30) controls, respectively. Box-and-whisker plots are shown with the x indicating the mean and circles indicating individual data points. Note: * indicates p < 0.05, as determined by Student’s t-test.
Figure 2
Figure 2
Inducing Glut1RNAi in Drosophila neurons does not affect food consumption. Relative feeding was measured in nSyb-Gal4>Glut1RNAi-TRiP (n = 50) and nSyb-Gal4>Glut1RNAi-VDRC (n = 25) flies and compared to nSyb-Gal4>LucRNAi (n = 50) and nSyb-Gal4>GFPRNAi (n = 27) controls, respectively. Box-and-whisker plots are shown with the x indicating the mean and circles indicating individual data points. ns indicates no statistical significance as determined by Student’s t-test.
Figure 3
Figure 3
Inducing RNAi to the Glut1 gene in all Drosophila neurons decreases Ilp3 and Ilp5 expression. Relative expression of (A) Ilp2, (B) Ilp3, and (C) llp5 normalized by relative expression of rp49 was measured in RNA isolated from whole nSyb-Gal4>Glut1RNAi-TRiP (n = 6) and nSyb-Gal4>Glut1RNAi-VDRC (n = 10) flies and compared to nSyb-Gal4>LucRNAi (n = 8) and nSyb-Gal4>GFPRNAi (n = 10) controls, respectively. Box-and-whisker plots are shown with the x indicating the mean and circles indicating individual data points. Note: * indicates p < 0.05 and ns indicates no statistical difference, as determined by Student’s t-test.
Figure 4
Figure 4
Inducing RNAi in the Glut1 gene in Drosophila insulin-producing neurons decreases whole-organism TAG and glycogen storage. (A) TAG and (B) glycogen normalized by protein content were measured in whole Ilp2-Gal4>Glut1RNAi-TRiP (n = 37) and Ilp2-Gal4>Glut1RNAi-VDRC (n = 24) flies and compared to Ilp2-Gal4>LucRNAi (n = 33) and Ilp2-Gal4>GFPRNAi (n = 24) controls, respectively. Box-and-whisker plots are shown with the x indicating the mean and circles indicating individual data points. Note: * indicates p < 0.05, as determined by Student’s t-test.
Figure 5
Figure 5
Inducing RNAi in the Glut1 gene in Drosophila insulin-producing neurons decreases Ilp3 and Ilp5 expression. Relative expression of (A) Ilp2, (B) Ilp3, and (C) Ilp5 normalized by relative expression of rp49 were measured in RNA isolated from whole Ilp2-Gal4>Glut1RNAi-TRiP (n = 22) and Ilp2-Gal4>Glut1RNAi-VDRC (n = 7) flies and compared to Ilp2-Gal4>LucRNAi (n = 25) and Ilp2-Gal4>GFPRNAi (n = 9) controls, respectively. Box-and-whisker plots are shown with the x indicating the mean. Note: * indicates p < 0.05 and ns indicates no statistical significance, as determined by Student’s t-test.
Figure 6
Figure 6
Ilp3 mutants have blunted TAG storage. TAG normalized by protein content was measured in Ilp3 mutants (n = 48) and Ilp5 mutants (n = 41) and compared to w1118 control flies (n = 100). Box-and-whisker plots are shown with the x indicating the mean and circles indicating individual data points. Note: * indicates a p < 0.05 and ns indicates no statistical significance, as determined by one-way ANOVA with post hoc Tukey test.
Figure 7
Figure 7
Ilp3 mutants and Ilp5 mutants have blunted glycogen storage. Glycogen normalized by protein content was measured in Ilp3 mutants (n = 48) and Ilp5 mutants (n = 41) and compared to w1118 control flies (n = 100). Box-and-whisker plots are shown with the x indicating the mean and circles indicating individual data points. Note: * indicates a p < 0.05, as determined by one-way ANOVA with post hoc Tukey test.
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