Insulin-Like Peptides Regulate Feeding Preference and Metabolism in Drosophila

Abstract

Fruit flies have eight identified Drosophila insulin-like peptides (DILPs) that are involved in the regulation of carbohydrate concentrations in hemolymph as well as in accumulation of storage metabolites. In the present study, we investigated diet-dependent roles of DILPs encoded by the genes dilp1–5, and dilp7 in the regulation of insect appetite, food choice, accumulation of triglycerides, glycogen, glucose, and trehalose in fruit fly bodies and carbohydrates in hemolymph. We have found that the wild type and the mutant lines demonstrate compensatory feeding for carbohydrates. However, mutants on dilp2,3, dilp3, dilp5, and dilp7 showed higher consumption of proteins on high yeast diets. To evaluate metabolic differences between studied lines on different diets we applied response surface methodology. High nutrient diets led to a moderate increase in concentration of glucose in hemolymph of the wild type flies. Mutations on dilp genes changed this pattern. We have revealed that the dilp2 mutation led to a drop in glycogen levels independently on diet, lack of dilp3 led to dramatic increase in circulating trehalose and glycogen levels, especially at low protein consumption. Lack of dilp5 led to decreased levels of glycogen and triglycerides on all diets, whereas knockout on dilp7 caused increase in glycogen levels and simultaneous decrease in triglyceride levels at low protein consumption. Fruit fly appetite was influenced by dilp3 and dilp7 genes. Our data contribute to the understanding of Drosophila as a model for further studies of metabolic diseases and may serve as a guide for uncovering the evolution of metabolic regulatory pathways.

Glucose Availability Alters Gene and Protein Expression of Several Newly Classified and Putative Solute Carriers in Mice Cortex Cell Culture and D. melanogaster

“…Not all putative SLCs included in the study were conserved in flies, however, a few of them had a clear orthologue to the human and mouse sequences: Mfsd1 ( mrva and CG12194 ), Mfsd6 ( jef ), Mfsd8 ( Cln7 ), Slc22a32 ( rtet ), Mfsd11 ( CG18549 ), Mfsd14a ( CG11537 ), and Unc93a ( CG4928 ). General markers known to be involved in metabolism and sugar pathways were also studied; Akh , AkhR ( Galikova et al, 2015 ), Gapdh1 , Gapdh2 ( Sun et al, 1988 ; Wojtas et al, 1992 ), Ilp5 ( Semaniuk et al, 2018 ), Ilp6 ( Bai et al, 2012 ) and InR ( Chen et al, 1996 ; Li et al, 2014 ), Figures 7A,B and Supplementary Figure 7 . Adult male flies were subjected to 0 h (controls), 3 h and 12 h of starvation as well as refeeding after 3 h and 12 h of starvation.…”

Genetic manipulation of insulin/insulin-like growth factor signaling pathway activity has sex-biased effects onDrosophilabody size

“…While Dilp1, Dilp2, Dilp3 and Dilp5 are all produced by the IPCs, previous studies have uncovered significant differences in regulation, secretion, and phenotypic effects of these IPC-derived Dilps (Brogiolo et al, 2001;Zhang et al, 2009;Okamoto et al, 2009;Grönke et al, 2010;Cognigni et al, 2011;Stafford et al, 2012;Bai et al, 2012;Linneweber et al, 2014;Cong et al, 2015;Liu et al, 2016;Nässel & Vanden Broeck, 2016;Post et al, 2018Post et al, , 2019Semaniuk et al, 2018;Ugrankar et al, 2018;Brown et al, 2020). We therefore wanted to determine the individual contributions of IPC-derived Dilps to body size in each sex.…”

Insulin Receptor Substrate Gene Knockdown Accelerates Behavioural Maturation and Shortens Lifespan in Honeybee Workers

“…Similar effects are observed with molecular and pharmacological interventions that suppress the conserved, nutrient sensing insulin/insulin-like signalling (IIS) and target of rapamycin (TOR) pathways [5,6,7]. Signalling through IIS/TOR pathways is upregulated in response to food intake and high nutrient stores [8,9], and can lead to further changes in food-related behaviours [10,11,12]. Dietary restrictions and IIS/TOR suppression may involve the same mechanisms to extend lifespan, with nutrient sensing mediating the effects of dietary restriction on aging and longevity [13,14].…”