Metformin-induced AMPK activation suppresses larval growth and molting probably by disrupting 20E synthesis and glycometabolism in fall webworm, Hyphantria cunea Drury

Zou, Haifeng; Zou, Hang; Li, Xingpeng; Qiu, Qian; Geng, Nannan; Zhang, Bi-Han; Yan, Gai-Ge; Zhang, Zhidong; Zhang, Sheng‐Yu; Yao, Bin; Zhang, Guocai; Zou, Chuanshan

doi:10.1016/j.pestbp.2022.105083

Cited by 7 publications

(3 citation statements)

References 60 publications

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“…The key role of AMPK genes in the regulation of various key parameters has been previously reported. For instance, the ecdysteroids signaling plays a major role in insect molting and metamorphosis, which is triggered by the binding of 20E to a heterodimer composed of EcR and ultra spiracle (USP) [24]. The present study revealed the AMPK role in inducing the physiological parameters of A. lucorum by dominant expression in all developmental stages with peaks correlating with the ecdysteroids pulse.…”

Section: Ampk Fine-tune a Lucorum Physiologymentioning

confidence: 55%

“…AMPK, in addition, also plays an important role in insect development, tissue growth, molting, and autophagy [23]. In recent decades the AMPK gene has been functionally characterized in numerous organisms such as Hyphantria cunea [24], B. mori [25], Drosophila melanogaster [26], Homo sapiens [27], and so on; however, the 20E-induced AMPK phosphorylation drives developmental programming, ecdysis, and metamorphosis in A. lucorum have not been properly understood.…”

Section: Discussionmentioning

confidence: 99%

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Adenosine Monophosphate-Activated Protein Kinase (AMPK) Phosphorylation Is Required for 20-Hydroxyecdysone Regulates Ecdysis in Apolygus lucorum

Tan

Xiao

Zhao

et al. 2023

IJMS

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The plant mirid bug Apolygus lucorum is an omnivorous pest that can cause considerable economic damage. The steroid hormone 20-hydroxyecdysone (20E) is mainly responsible for molting and metamorphosis. The adenosine monophosphate-activated protein kinase (AMPK) is an intracellular energy sensor regulated by 20E, and its activity is regulated allosterically through phosphorylation. It is unknown whether the 20E-regulated insect’s molting and gene expression depends on the AMPK phosphorylation. Herein, we cloned the full-length cDNA of the AlAMPK gene in A. lucorum. AlAMPK mRNA was detected at all developmental stages, whereas the dominant expression was in the midgut and, to a lesser extent, in the epidermis and fat body. Treatment with 20E and AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AlCAR) or only AlCAR resulted in activation of AlAMPK phosphorylation levels in the fat body, probed with an antibody directed against AMPK phosphorylated at Thr172, enhancing AlAMPK expression, whereas no phosphorylation occurred with compound C. Compared to compound C, 20E and/or AlCAR increased the molting rate, the fifth instar nymphal weight and shortened the development time of A. lucorum in vitro by inducing the expression of EcR-A, EcR-B, USP, and E75-A. Similarly, the knockdown of AlAMPK by RNAi reduced the molting rate of nymphs, the weight of fifth-instar nymphs and blocked the developmental time and the expression of 20E-related genes. Moreover, as observed by TEM, the thickness of the epidermis of the mirid was significantly increased in 20E and/or AlCAR treatments, molting spaces began to form between the cuticle and epidermal cells, and the molting progress of the mirid was significantly improved. These composite data indicated that AlAMPK, as a phosphorylated form in the 20E pathway, plays an important role in hormonal signaling and, in short, regulating insect molting and metamorphosis by switching its phosphorylation status.

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Section: Ampk Fine-tune a Lucorum Physiologymentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Adenosine Monophosphate-Activated Protein Kinase (AMPK) Phosphorylation Is Required for 20-Hydroxyecdysone Regulates Ecdysis in Apolygus lucorum

Tan

Xiao

Zhao

et al. 2023

IJMS

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“…For instance, AMPK could promote protein phosphatase 2A (PP2A) during Bombyx mori and D. melanogaster metamorphosis in response to high amounts of 20-hydroxyecdysone (20E), resulting in limiting growth speed and body weight [ 39 ]. When AMPK signaling is triggered, the synthesis of 20E in Hyphantria cunea larvae is blocked, which leads to the delay of larval metamorphosis [ 50 ]. Thus, to explore the involvement of AMPK in the metamorphosis of marine invertebrates, the inhibitor or activator of AMPK was used in the metamorphosis experiment of M. coruscus , and the AMPK genes were knocked down with siRNAs.…”

Section: Discussionmentioning

confidence: 99%

AMPK Promotes Larval Metamorphosis of Mytilus coruscus

Zhang

Wang

et al. 2022

Genes

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Metamorphosis is a critical process in the transition from planktonic life to benthic life for marine invertebrates, which is accompanied by a large amount of energy consumption. Previous studies have proved that AMP-activated protein kinase (AMPK), as a vital energy regulator, plays a prominent role in mediating the growth and development of terrestrial animals. However, its function in the growth and development of marine invertebrates, especially in metamorphosis, remains elusive. This study explored the function of AMPK in the larval metamorphosis of Mytilus coruscus. The full-length cDNA of AMPK genes in M. coruscus was cloned and characterized, which is composed of three subunits, McAMPKα, McAMPKβ, and McAMPKγ. Pharmacological tests demonstrated that through the application of an AMPK activator, AMP substantially enhanced the larval metamorphosis rate (p < 0.05). By contrast, the larval metamorphosis rate decreased significantly after being treated with the AMPK inhibitor Compound C (p < 0.05). McAMPK gene knock-down resulted in a reduction in McAMPK gene expression (p < 0.05), and the larval metamorphosis of M. coruscus was significantly restrained (p < 0.05). These results indicated that AMPK signaling is vital in the larval metamorphosis of M. coruscus, which advances further understanding in exploring the molecular mechanisms in the metamorphosis of marine invertebrate larvae.

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Chlorbenzuron downregulated HcLCP‐17 expression by depressing two 20E‐responsive transcription factors Br‐C and βFTZ‐F1 in Hyphantria cunea (Lepidoptera: Erebidae) larvae

Zhao,

Zhang,

Zou

et al. 2024

Pest Management Science

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BACKGROUNDCuticular proteins (CPs) play essential roles in forming cuticular structures in insects. However, the specific functions and regulatory mechanisms of CPs remain largely unexplored. In this study, the Larval cuticular protein 17 (HcLCP‐17) gene was identified from Hyphantria cunea, a highly destructive and polyphagous forest pest. To investigate the role of HcLCP‐17 in cuticular function and transcriptional regulation mediated by 20E‐responsive transcription factors (ERTFs), we employed RNA interference (RNAi) and yeast one‐hybrid assay techniques. Additionally, we examined the molecular mechanism by which chlorbenzuron, a type of benzoylphenylurea (BPU) that functions as a chitin synthesis inhibitor (CSI), affects the 20E signaling pathway and ultimately regulates HcLCP‐17 expression.RESULTSHcLCP‐17 encodes a polypeptide consisting of 393 amino acids, which includes a chitin‐binding domain. Silencing HcLCP‐17 resulted in a disturbance in the structural organization of the larval cuticle and a notable reduction in chitin levels. HcLCP‐17 expression was controlled by the interaction between Broad‐Complex (Br‐C) and beta Fushi Tarazu Factor‐1 (βFTZ‐F1) with its promoter fragment. Furthermore, the inhibitory effect of chlorbenzuron on HcLCP‐17 expression was found to be potentially mediated by Br‐C and βFTZ‐F1.CONCLUSIONThe study presents a novel mode of action for the 20E signaling pathway in regulating the expression of CPs and reveals the potential mode‐of‐action of BPUs in insect cuticles. These findings provide a theoretical basis for future utilization of LCP‐17 as a pesticide target making a significant contribution to the development of effective pest management strategies. © 2024 Society of Chemical Industry.

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Metformin-induced AMPK activation suppresses larval growth and molting probably by disrupting 20E synthesis and glycometabolism in fall webworm, Hyphantria cunea Drury

Cited by 7 publications

References 60 publications

Adenosine Monophosphate-Activated Protein Kinase (AMPK) Phosphorylation Is Required for 20-Hydroxyecdysone Regulates Ecdysis in Apolygus lucorum

Adenosine Monophosphate-Activated Protein Kinase (AMPK) Phosphorylation Is Required for 20-Hydroxyecdysone Regulates Ecdysis in Apolygus lucorum

AMPK Promotes Larval Metamorphosis of Mytilus coruscus

Chlorbenzuron downregulated HcLCP‐17 expression by depressing two 20E‐responsive transcription factors Br‐C and βFTZ‐F1 in Hyphantria cunea (Lepidoptera: Erebidae) larvae

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