Dataset Information

AKH Signaling in D. melanogaster Alters Larval Development in a Nutrient-Dependent Manner That Influences Adult Metabolism.

ABSTRACT: Metabolism, growth, and development are intrinsically linked, and their coordination is dependent upon inter-organ communication mediated by anabolic, catabolic, and steroid hormones. In Drosophila melanogaster, the corpora cardiaca (CC) influences metabolic homeostasis through adipokinetic hormone (AKH) signaling. AKH has glucagon-like properties and is evolutionarily conserved in mammals as the gonadotropin-releasing hormone, but its role in insect development is unknown. Here we report that AKH signaling alters larval development in a nutrient stress-dependent manner. This activity is regulated by the locus dg2, which encodes a cGMP-dependent protein kinase (PKG). CC-specific downregulation of dg2 expression delayed the developmental transition from larval to pupal life, and altered adult metabolism and behavior. These developmental effects were AKH-dependent, and were observed only in flies that experienced low nutrient stress during larval development. Calcium-mediated vesicle exocytosis regulates ecdysteroid secretion from the prothoracic gland (PG), and we found that AKH signaling increased cytosolic free calcium levels in the PG. We identified a novel pathway through which PKG acts in the CC to communicate metabolic information to the PG via AKH signaling. AKH signaling provides a means whereby larval nutrient stress can alter developmental trajectories into adulthood.

SUBMITTER: Hughson BN

PROVIDER: S-EPMC7940354 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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AKH Signaling in <i>D. melanogaster</i> Alters Larval Development in a Nutrient-Dependent Manner That Influences Adult Metabolism.

Hughson Bryon N BN Shimell MaryJane M O'Connor Michael B MB

Frontiers in physiology 20210223

Metabolism, growth, and development are intrinsically linked, and their coordination is dependent upon inter-organ communication mediated by anabolic, catabolic, and steroid hormones. In <i>Drosophila melanogaster</i>, the corpora cardiaca (CC) influences metabolic homeostasis through adipokinetic hormone (AKH) signaling. AKH has glucagon-like properties and is evolutionarily conserved in mammals as the gonadotropin-releasing hormone, but its role in insect development is unknown. Here we report ...[more]

PMID: 33708137

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Project description:Folic acid, an oxidized synthetic pro-vitamin B9, is widely used in vitamin supplement formulations and food fortification to maintain optimal folate status in humans. Studies on folic acid (FA) efficiency in improving folate status and correcting folate deficiency pathologies are abundant, but precise knowledge of FA effects on human and animal tissues is not available. In our recent study, 10-week-old wild-type and CerS6 knockout (KO) mice were placed on FA-deficient, control, or FA over-supplemented diet for 4 weeks. Untargeted metabolomics characterization of mouse liver, brain, and testes tissues after the dietary treatment revealed profound effects of FA on the liver metabolome. Here, we present the analysis of dietary FA effects on tissue concentrations of other vitamins in mice. Despite the expectation that identical dietary supply of the vitamins (excluding FA) to each group should support similar tissue vitamins concentrations, metabolomics data demonstrate significant alterations of tissue concentrations of multiple vitamins by different levels of FA supplementation that were sex- and genotype-dependent. Moreover, we found significant differences in the liver concentration of retinol, thiamin diphosphate, pantetheine, pyridoxal, and pyridoxamine between males and females. While the liver had more changes in vitamins and vitamin derivative levels, the brain tissue and testes also showed changes linked to FA supplementation. Over-supplementation with FA had negative effects on concentrations of vitamins A, B1, B2, and B6, or their metabolites in the liver, but increased intermediates in coenzyme A (CoA) biosynthesis, as well as gamma/beta-tocopherol and phosphorylated forms of B6 in the CerS6 KO brain. Overall, our data demonstrate that dietary FA supplementation significantly affects the metabolism of other vitamins, and that these effects depend on the CerS6 status and sex of the animal. Further research is required to determine whether the observed effects are specific to FA, and the mechanisms that are involved.

Dataset Information

AKH Signaling in D. melanogaster Alters Larval Development in a Nutrient-Dependent Manner That Influences Adult Metabolism.

Publications

AKH Signaling in <i>D. melanogaster</i> Alters Larval Development in a Nutrient-Dependent Manner That Influences Adult Metabolism.

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