GO:0097003 adipokinetic hormone receptor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0097003 (adipokinetic hormone receptor activity) is a molecular function defined as binding to an adipokinetic hormone (AKH) to initiate a change in cell activity.
• AKH receptors are G protein-coupled receptors that mobilize sugar and lipids from the insect fat body during energy-requiring activities such as flight and locomotion.
• The receptor is essential for trehalose homeostasis, vitellogenin uptake by oocytes, and larval food intake and development in multiple insect species [2,4].
• AKH receptor signaling regulates triacylglycerol mobilization and sexual behavior in the oriental fruit fly Bactrocera dorsalis.
• The receptor has been functionally characterized in diverse insects including Plutella xylostella, Ostrinia furnacalis, Sarcophaga crassipalpis, and the gastropod Aplysia californica [1,2,3,6].
• Molecular modelling of the Carausius morosus AKH receptor provides structural insights into agonist binding and receptor activation.
Description
Adipokinetic hormone receptor activity (GO:0097003) is a molecular function that mediates the cellular response to adipokinetic hormones (AKHs), a family of peptide hormones central to energy homeostasis in metazoa. In insects, AKHs are released into the hemolymph and act on the fat body to mobilize carbohydrates and lipids during energy-demanding activities such as flight and locomotion. The receptor itself is a G protein-coupled receptor (GPCR) that binds AKH and initiates intracellular signaling cascades, thereby linking hormonal signals to metabolic reprogramming [1,5]. This function is critical for maintaining hemolymph sugar homeostasis and for coordinating energy supply with behavioral and developmental demands [4,8]. Researchers study GO:0097003 to understand how organisms balance energy storage and expenditure, how hormonal signals are transduced across cell membranes, and how these processes can be targeted for pest control or metabolic disease intervention [2,3,6]. The receptor has been identified and functionally characterized in a wide range of insects, including the diamondback moth Plutella xylostella, the Asian corn borer Ostrinia furnacalis, the flesh fly Sarcophaga crassipalpis, and the brown planthopper Nilaparvata lugens [2,3,4,6]. More recently, an AKH receptor ortholog was authenticated in the gastropod Aplysia californica, extending the evolutionary reach of this signaling system beyond insects. Because AKH receptor activity sits at the interface of nutrient sensing, metabolism, and reproduction, it represents a powerful experimental node for dissecting GPCR pharmacology, endocrine regulation, and organismal physiology [5,7]. This article synthesizes authoritative QuickGO annotation data and verified PubMed literature to provide a research-grade overview of the term, its mechanism, key genes, disease relevance, and modern methods for its study.
adipokinetic hormone receptor activity At A Glance
| GO ID | GO:0097003 |
|---|---|
| GO term | adipokinetic hormone receptor activity |
| Ontology | molecular_function |
| Synonym | AKH receptor activity |
| Major function | Binding to adipokinetic hormones to initiate intracellular signaling that mobilizes sugar and lipids |
| Organismal context | Metazoa, with best-characterized roles in insects and emerging evidence in gastropods |
| Physiological roles | Trehalose homeostasis, lipid mobilization, vitellogenin uptake, larval development, sexual behavior |
| Receptor class | G protein-coupled receptor (GPCR) |
| Agonist | Adipokinetic hormone (AKH) peptide |
What Is GO:0097003?
Adipokinetic hormone receptor activity (GO:0097003) is the molecular function of combining with an adipokinetic hormone (AKH) to initiate a change in cell activity. AKHs are protein or peptide hormones that regulate sugar and fat homeostasis in metazoa. In insects, AKH receptor activation mobilizes trehalose and lipids from the fat body during energy-requiring activities such as flight and locomotion, and it contributes to hemolymph sugar homeostasis [4,8]. The term is synonymous with AKH receptor activity and is classified under molecular_function in the Gene Ontology.
Why Is adipokinetic hormone receptor activity Important in Cell Biology?
GO:0097003 is important because it defines the molecular entry point for a hormonal system that governs energy balance in metazoa. In insects, AKH receptor signaling is required for mobilizing trehalose and lipids during flight and locomotion, and it directly influences hemolymph sugar homeostasis [4,5]. Disruption of this receptor impairs larval food intake and development, as shown in Plutella xylostella, and affects triacylglycerol mobilization and sexual behavior in Bactrocera dorsalis. The receptor also mediates vitellogenin uptake by oocytes in Nilaparvata lugens, linking energy metabolism to reproduction. Because AKH receptors are GPCRs, they are tractable pharmacological targets, and understanding their activity informs both basic endocrinology and applied pest management [3,6,7].
• Controls hemolymph sugar homeostasis by mobilizing trehalose from the fat body.
• Regulates lipid mobilization, including triacylglycerol breakdown, during energy-requiring activities.
• Is required for larval food intake and normal development in lepidopteran pests.
• Mediates vitellogenin uptake by oocytes, connecting metabolism to reproduction.
• Modulates sexual behavior in the oriental fruit fly Bactrocera dorsalis.
• Functions as a GPCR, making it a druggable target for pharmacological intervention [1,5].
• Has been characterized in diverse insect orders, enabling comparative endocrinology [3,6].
• Emerging evidence extends AKH receptor function to gastropods, broadening evolutionary relevance.
• Molecular models of the receptor provide a basis for structure-guided agonist design.
• Serves as a model for studying nutrient-sensing and stress-responsive endocrine circuits.
What Happens During adipokinetic hormone receptor activity?
Hormone binding and receptor activation
In simple terms: The AKH hormone docks onto its receptor on the cell surface, switching the receptor on.
Adipokinetic hormone receptor activity begins when an AKH peptide binds to the extracellular domain of the receptor, a G protein-coupled receptor [1,5]. This binding event induces a conformational change that activates the receptor and promotes interaction with heterotrimeric G proteins. In insects, AKH is released into the hemolymph from intrinsic nutrient-sensing cells and travels to target tissues such as the fat body. The activated receptor then initiates intracellular signaling cascades that lead to metabolic changes [1,5].
Intracellular signaling and second messenger generation
In simple terms: Once switched on, the receptor triggers a relay of signals inside the cell.
Activated AKH receptors couple to G proteins and stimulate downstream effectors, typically leading to the production of second messengers such as cyclic AMP and calcium ions [1,5]. These second messengers activate protein kinases and other signaling enzymes that propagate the hormonal signal. The specific signaling pathways can vary by species and tissue, but the core outcome is a rapid change in cellular activity that supports energy mobilization [1,4].
Mobilization of trehalose and lipids
In simple terms: The cell breaks down stored sugar and fat to release energy.
A major physiological outcome of AKH receptor activity is the mobilization of trehalose, the main circulating sugar in insects, and lipids such as triacylglycerols [4,8]. In Nilaparvata lugens, AKH receptor signaling mediates trehalose homeostasis to promote vitellogenin uptake by oocytes. In Bactrocera dorsalis, the receptor regulates triacylglycerol mobilization, providing energy for activities including sexual behavior. These metabolic effects ensure that energy substrates are available during demanding periods such as flight and reproduction [5,8].
Regulation of feeding and development
In simple terms: The receptor helps decide when to eat and how fast to grow.
AKH receptor activity is required for normal larval food intake and development, as demonstrated in Plutella xylostella. Knockdown or mutation of the receptor reduces feeding and impairs growth, indicating that the receptor couples nutrient sensing to developmental progression. In Ostrinia furnacalis larvae parasitized by Macrocentrus cingulum, the receptor is functionally linked to parasitism-induced metabolic changes. These findings highlight the receptor as a key regulator of organismal energy balance and life-history transitions [2,3].
Key Genes Involved in GO:0097003 adipokinetic hormone receptor activity
The following genes and proteins are central to adipokinetic hormone receptor activity and its downstream physiological effects, based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| AKHR (Plutella xylostella) | Receptor for AKH; required for larval food intake and development | Target for pest control; model for feeding regulation |
| AKHR (Ostrinia furnacalis) | AKH receptor in larvae parasitized by Macrocentrus cingulum | Study of host-parasitoid metabolic interactions |
| AKHR (Nilaparvata lugens) | Mediates trehalose homeostasis and vitellogenin uptake by oocytes | Link between metabolism and reproduction |
| AKHR (Bactrocera dorsalis) | Regulates triacylglycerol mobilization and sexual behavior | Model for lipid mobilization and behavior |
| AKHR (Sarcophaga crassipalpis) | Characterized AKH receptor in anautogenous flesh fly | Comparative endocrinology of reproduction and diapause |
| AKHR (Carausius morosus) | Molecular model of AKH receptor and endogenous agonist | Structure-function studies of GPCR activation |
| AKHR (Aplysia californica) | Authenticated lophotrochozoan AKH receptor | Evolutionary expansion of AKH signaling |
| AKH (adipokinetic hormone) | Peptide hormone ligand for AKHR | Agonist design and hormone-receptor interaction |
| G protein subunits | Mediate signal transduction from activated AKHR | GPCR signaling mechanisms [1,5] |
| Adenylyl cyclase | Produces cAMP second messenger downstream of AKHR | Second messenger studies |
| Protein kinase A | Phosphorylates targets to mobilize energy stores | Metabolic signaling |
| Trehalose synthesis enzymes | Produce trehalose in response to AKHR signaling | Sugar homeostasis |
| Triacylglycerol lipases | Break down stored fat upon AKHR activation | Lipid mobilization |
| Vitellogenin | Yolk protein taken up by oocytes; regulated by AKHR | Reproduction and nutrient allocation |
| Nutrient-sensing cells | Produce and release AKH | Endocrine regulation of metabolism |
| Fat body | Major target tissue for AKH receptor signaling | Energy mobilization [5,8] |
How Is adipokinetic hormone receptor activity Regulated?
Adipokinetic hormone receptor activity is regulated at multiple levels. Hormone availability is controlled by the intrinsic nutrient-sensing AKH-producing cells, which modulate metabolism, activity, and stress responses. Receptor expression levels can vary with developmental stage and nutritional state, as seen in Plutella xylostella where the receptor is required for larval food intake. In parasitized Ostrinia furnacalis larvae, the receptor is functionally modulated by the presence of the parasitoid Macrocentrus cingulum. Additionally, receptor activity is influenced by the availability of downstream G proteins and second messenger systems, which can be tuned by cellular metabolic status [1,5]. These layers of regulation ensure that energy mobilization is matched to organismal demand.
adipokinetic hormone receptor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| AKHR (Nilaparvata lugens) | Reproductive impairment due to defective vitellogenin uptake | Knockout in N. lugens to assess fecundity |
| AKHR (Bactrocera dorsalis) | Metabolic dysregulation and altered sexual behavior | Knockdown or knockout in B. dorsalis |
| AKHR (Plutella xylostella) | Larval feeding and developmental failure | CRISPR knockout in P. xylostella |
| AKHR (Ostrinia furnacalis) | Parasitism-induced metabolic changes | Knockout in parasitized larvae |
| AKHR (Aplysia californica) | Evolutionary conservation of AKH signaling | Heterologous expression and functional assays |
Metabolic disorders and energy imbalance
While AKH receptor activity is best characterized in insects, its core function in mobilizing sugar and lipids parallels pathways relevant to human metabolic disorders. Disruption of AKH receptor signaling in insects leads to impaired trehalose homeostasis and lipid mobilization, phenotypes that resemble aspects of dyslipidemia and impaired glucose regulation in humans [4,8]. Studying this receptor provides a comparative framework for understanding how hormonal control of energy stores can go awry.
Reproductive dysfunction
AKH receptor activity is linked to reproduction through its role in vitellogenin uptake by oocytes in Nilaparvata lugens. When receptor function is compromised, nutrient allocation to developing oocytes is impaired, which can reduce fecundity. This connection between metabolism and reproduction has parallels in human reproductive disorders where energy balance affects fertility [4,5].
Pest management and vector control
Because AKH receptor activity is essential for larval development and feeding in pests such as Plutella xylostella and Bactrocera dorsalis, it represents a potential target for insect control strategies [2,8]. Small molecules or peptides that modulate receptor activity could disrupt energy homeostasis and reduce pest populations [2,3,6]. This applied dimension makes the receptor a focus for agrochemical and vector-control research [2,8].
From adipokinetic hormone receptor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does AKHR loss impair larval feeding and development? | CRISPR knockout in Plutella xylostella |
| Does AKHR regulate trehalose homeostasis and vitellogenin uptake? | RNAi knockdown in Nilaparvata lugens |
| Does AKHR control triacylglycerol mobilization and sexual behavior? | Knockout or knockdown in Bactrocera dorsalis |
| How does AKHR structure determine agonist binding? | Point mutations in Carausius morosus AKHR followed by molecular modelling |
| Is AKHR function conserved in non-insect metazoa? | Knock-in or overexpression of Aplysia californica AKHR in heterologous cells |
| Does AKHR mediate host-parasitoid metabolic crosstalk? | Knockout in Ostrinia furnacalis larvae parasitized by Macrocentrus cingulum |
How to Study the adipokinetic hormone receptor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNAi knockdown | Reduction of AKHR mRNA and protein | Loss-of-function studies in insects |
| CRISPR knockout | Complete loss of AKHR function | Heritable knockout lines for developmental studies |
| Heterologous expression | Receptor activation and second messenger production | Pharmacological characterization of AKHR |
| Molecular modelling | Predicted ligand-receptor interactions | Structure-function analysis |
| Metabolic assays | Trehalose and triacylglycerol levels | Energy homeostasis studies [4,8] |
| Behavioral assays | Feeding, locomotion, sexual behavior | Linking receptor activity to behavior [2,8] |
| Quantitative PCR | AKHR gene expression levels | Tissue and stage-specific expression profiling [3,6] |
| Western blotting | AKHR protein abundance | Validation of knockdown or overexpression |
RNA interference and CRISPR knockout
RNA interference (RNAi) and CRISPR-based knockout are widely used to reduce or eliminate AKH receptor expression and assess loss-of-function phenotypes. In Nilaparvata lugens, RNAi knockdown of AKHR revealed its role in trehalose homeostasis and vitellogenin uptake. In Plutella xylostella, CRISPR knockout demonstrated the receptor's requirement for larval food intake and development. These approaches are essential for establishing causality between receptor activity and organismal phenotypes [2,4].
Heterologous expression and signaling assays
Heterologous expression of AKH receptors in cell lines allows direct measurement of receptor activation and downstream signaling. For example, the Aplysia californica AKH receptor was authenticated by expressing it in a heterologous system and testing its response to AKH peptides. Such assays typically monitor second messenger production, such as cAMP or calcium mobilization, to quantify receptor activity [1,5]. These methods are critical for pharmacological profiling of agonists and antagonists.
Molecular modelling and structural analysis
Molecular modelling and docking studies provide structural insights into how AKH receptors bind their ligands and undergo activation. The Carausius morosus AKH receptor was modelled together with its endogenous agonist to predict key interaction residues. These computational approaches complement experimental mutagenesis and can guide the design of novel receptor modulators.
Metabolic and behavioral phenotyping
Measuring trehalose, triacylglycerol, and other energy substrates, combined with behavioral assays, reveals the physiological consequences of altered AKH receptor activity. In Bactrocera dorsalis, receptor knockdown affected triacylglycerol mobilization and sexual behavior. In Nilaparvata lugens, trehalose levels and vitellogenin uptake were quantified to link receptor function to reproduction. Such phenotyping is essential for translating molecular findings into organismal outcomes [4,8].
How CRISPR Can Be Used to Study GO:0097003 adipokinetic hormone receptor activity
Knockout
CRISPR knockout of the AKH receptor gene is used to create null mutants that lack receptor activity. In Plutella xylostella, knockout of AKHR resulted in impaired larval food intake and developmental defects, establishing the receptor as essential for normal growth. Such knockout lines are valuable for studying the full range of physiological processes controlled by AKH signaling, including metabolism, feeding, and reproduction [2,4].
Point Mutation
Point mutations can be introduced into the AKH receptor gene to dissect structure-function relationships. For example, mutations in residues predicted to contact the ligand can test their role in agonist binding and receptor activation, as suggested by molecular modelling of the Carausius morosus receptor. These targeted mutations allow precise interrogation of the receptor's signaling mechanism without abolishing protein expression.
Knock-in
Knock-in strategies can be used to tag the endogenous AKH receptor with fluorescent or affinity markers, enabling real-time visualization and biochemical purification. Alternatively, species-specific orthologs can be knocked into a model organism to test functional conservation, as demonstrated by the authentication of the Aplysia californica AKH receptor in a heterologous context. Knock-in models facilitate studies of receptor localization, trafficking, and interaction partners.
Overexpression
Overexpression of the AKH receptor in cell lines or transgenic organisms can amplify signaling output and facilitate biochemical assays. Heterologous overexpression was key to characterizing the Aplysia californica receptor and confirming its responsiveness to AKH peptides. Overexpression systems are also useful for screening small-molecule modulators of receptor activity [1,5].
How EDITGENE Supports adipokinetic hormone receptor activity Research
Researchers studying adipokinetic hormone receptor activity-related genes often need to determine whether a candidate gene is causally involved in receptor signaling, metabolism, or development. Establishing causality requires precise genetic tools that can knock out, mutate, tag, or overexpress the gene of interest in relevant cell and animal models. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for adipokinetic hormone receptor activity research.
Frequently Asked Questions About adipokinetic hormone receptor activity
What is adipokinetic hormone receptor activity?
Adipokinetic hormone receptor activity (GO:0097003) is the molecular function of binding to an adipokinetic hormone to initiate a change in cell activity, typically mobilizing sugar and lipids in insects [1,5].
What genes are involved in adipokinetic hormone receptor activity?
The primary gene is the AKH receptor (AKHR), which encodes a G protein-coupled receptor. Downstream genes include G protein subunits, adenylyl cyclase, protein kinase A, and metabolic enzymes for trehalose and lipid mobilization [1,4,5].
What is the GO ID for adipokinetic hormone receptor activity?
The Gene Ontology ID is GO:0097003, classified under molecular_function.
How does the adipokinetic hormone receptor work?
It binds AKH peptides, activates G protein signaling, and triggers second messenger cascades that mobilize trehalose and lipids from the fat body during energy-demanding activities [1,5].
Which insects have been used to study AKH receptor activity?
The receptor has been studied in Plutella xylostella, Ostrinia furnacalis, Nilaparvata lugens, Bactrocera dorsalis, Sarcophaga crassipalpis, and Carausius morosus, among others [2,3,4,6,7,8].
Is the AKH receptor found outside insects?
Yes, an AKH receptor ortholog has been authenticated in the gastropod Aplysia californica, indicating that this signaling system extends beyond insects.
What happens when AKH receptor activity is lost?
Loss of receptor activity impairs larval food intake and development, disrupts trehalose homeostasis, reduces vitellogenin uptake, and affects lipid mobilization and sexual behavior [2,4,8].
How can I study adipokinetic hormone receptor activity in the lab?
Common methods include RNAi knockdown, CRISPR knockout, heterologous expression with signaling assays, molecular modelling, and metabolic phenotyping [1,2,4,7].
What diseases are linked to adipokinetic hormone receptor activity?
While primarily studied in insects, the receptor's role in energy balance has parallels to human metabolic disorders such as dyslipidemia and impaired glucose regulation [4,5,8].
Can CRISPR be used to study AKH receptor function?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools for dissecting AKH receptor function in vivo and in vitro [2,7].
Conclusion
Adipokinetic hormone receptor activity (GO:0097003) is a fundamental molecular function that links hormonal signals to energy mobilization in metazoa. Through its role as a GPCR, the AKH receptor controls trehalose and lipid homeostasis, feeding, development, and reproduction, as demonstrated across multiple insect species and an emerging gastropod model [1,2,4,8]. Understanding this receptor provides insights into metabolic regulation, GPCR pharmacology, and potential applications in pest control [3,6,7]. Researchers can leverage CRISPR-based knockout, point mutation, knock-in, and overexpression models to dissect the precise roles of AKH receptors and their signaling partners. EDITGENE offers comprehensive services to accelerate these studies and support publication-ready discoveries.
References
- 1. Tsai PS et al.. 2024. Authentication of a lophotrochozoan adipokinetic hormone receptor in a Gastropod, Aplysia californica.. Gen Comp Endocrinol 345:114393 PMID: 37865149
- 2. Hou QL et al.. 2025. Adipokinetic hormone receptor is required for larval food intake and development of Plutella xylostella.. J Insect Physiol 167:104913 PMID: 41317840
- 3. Wang L et al.. 2024. Identification and Functional Analysis of Adipokinetic Hormone Receptor in Ostrinia furnacalis Guenée Larvae Parasitized by Macrocentrus cingulum.. Arch Insect Biochem Physiol 116(4):e22147 PMID: 39190556
- 4. Lu K et al.. 2018. Adipokinetic Hormone Receptor Mediates Trehalose Homeostasis to Promote Vitellogenin Uptake by Oocytes in Nilaparvata lugens.. Front Physiol 9:1904 PMID: 30687120
- 5. Nelson JM et al.. 2021. The Intrinsic Nutrient Sensing Adipokinetic Hormone Producing Cells Function in Modulation of Metabolism, Activity, and Stress.. Int J Mol Sci 22(14) PMID: 34299134
- 6. Bil M et al.. 2016. Characterization of the adipokinetic hormone receptor of the anautogenous flesh fly, Sarcophaga crassipalpis.. J Insect Physiol 89:52-9 PMID: 27063262
- 7. Jackson GE et al.. 2026. Molecular modelling of the adipokinetic hormone receptor from the stick insect Carausius morosus, and its endogenous agonist.. Sci Rep 16(1) PMID: 42332141
- 8. Hou QL et al.. 2017. Adipokinetic hormone receptor gene identification and its role in triacylglycerol mobilization and sexual behavior in the oriental fruit fly (Bactrocera dorsalis).. Insect Biochem Mol Biol 90:1-13 PMID: 28919559
