Increased Akt signaling in the mosquito fat body increases adult survivorship

Arik, Anam J.; Hun, Lewis V.; Quicke, Kendra M.; Piatt, Michael; Ziegler, Rolf; Scaraffia, Patricia Y.; Badgandi, Hemant B.; Riehle, Michael A.

doi:10.1096/fj.14-261479

Cited by 28 publications

(21 citation statements)

References 48 publications

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“…Curiously, introduction of exogenous insulin into the mosquito diet reduced Anopheles sp. lifespan [ 57 ], while overexpression of Akt in the mosquito fat body enhanced vector lifespan [ 58 ]. These results indicate that polyphenol extension of average lifespan may rely on the downregulation of insulin pathway which classically relies on AMPK activation.…”

Section: Discussionmentioning

confidence: 99%

Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan

et al. 2016

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BackgroundMosquitoes feed on plant-derived fluids such as nectar and sap and are exposed to bioactive molecules found in this dietary source. However, the role of such molecules on mosquito vectorial capacity is unknown. Weather has been recognized as a major determinant of the spread of dengue, and plants under abiotic stress increase their production of polyphenols.ResultsHere, we show that including polyphenols in mosquito meals promoted the activation of AMP-dependent protein kinase (AMPK). AMPK positively regulated midgut autophagy leading to a decrease in bacterial proliferation and an increase in vector lifespan. Suppression of AMPK activity resulted in a 6-fold increase in midgut microbiota. Similarly, inhibition of polyphenol-induced autophagy induced an 8-fold increase in bacterial proliferation. Mosquitoes maintained on the polyphenol diet were readily infected by dengue virus.ConclusionThe present findings uncover a new direct route by which exacerbation of autophagy through activation of the AMPK pathway leads to a more efficient control of mosquito midgut microbiota and increases the average mosquito lifespan. Our results suggest for the first time that the polyphenol content and availability of the surrounding vegetation may increase the population of mosquitoes prone to infection with arboviruses.

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Section: Discussionmentioning

confidence: 99%

Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan

et al. 2016

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“…Survivorship differences compared to controls were only observed when mosquitoes were fed blood and were abrogated when mosquitoes were fed only sugar. Interestingly, transgenic mosquitoes also showed increased expression of the fat body vitellogenin, which is a precursor protein to egg yolk (Arik et al, ). The lack of a trade‐off between reproduction and longevity as well as the enhancement of a reproductive protein tied to prolonged life is noteworthy.…”

Section: Lifespan Extension Via Lipid‐related Interventionsmentioning

confidence: 99%

The role of lipid metabolism in aging, lifespan regulation, and age‐related disease

2019

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An emerging body of data suggests that lipid metabolism has an important role to play in the aging process. Indeed, a plethora of dietary, pharmacological, genetic, and surgical lipid‐related interventions extend lifespan in nematodes, fruit flies, mice, and rats. For example, the impairment of genes involved in ceramide and sphingolipid synthesis extends lifespan in both worms and flies. The overexpression of fatty acid amide hydrolase or lysosomal lipase prolongs life in Caenorhabditis elegans, while the overexpression of diacylglycerol lipase enhances longevity in both C. elegans and Drosophila melanogaster. The surgical removal of adipose tissue extends lifespan in rats, and increased expression of apolipoprotein D enhances survival in both flies and mice. Mouse lifespan can be additionally extended by the genetic deletion of diacylglycerol acyltransferase 1, treatment with the steroid 17‐α‐estradiol, or a ketogenic diet. Moreover, deletion of the phospholipase A2 receptor improves various healthspan parameters in a progeria mouse model. Genome‐wide association studies have found several lipid‐related variants to be associated with human aging. For example, the epsilon 2 and epsilon 4 alleles of apolipoprotein E are associated with extreme longevity and late‐onset neurodegenerative disease, respectively. In humans, blood triglyceride levels tend to increase, while blood lysophosphatidylcholine levels tend to decrease with age. Specific sphingolipid and phospholipid blood profiles have also been shown to change with age and are associated with exceptional human longevity. These data suggest that lipid‐related interventions may improve human healthspan and that blood lipids likely represent a rich source of human aging biomarkers.

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“…To confirm the specificity of the assay, a no‐virus control was included where the membrane was not overlaid with CHIKV cell culture supernatant. Additionally, the membrane fractions used were subjected western blotting using antibodies to GAPDH (catalogue number PA1‐987; ThermoFisher Scientific), which is abundant in eukaryotic tissue fractions and has been used as a loading control in previously reported studies (Arik et al , ).…”

Section: Methodsmentioning

confidence: 99%

Understanding the mechanism of Chikungunya virus vector competence in three species of mosquitoes

Ghosh

Mullapudi

Bomanna

et al. 2019

Medical Vet Entomology

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Chikungunya virus (CHIKV) is primarily transmitted by Aedes spp. mosquitoes. The present study investigated vector competence for CHIKV in Aedes aegypti and Aedes albopictus mosquitoes found in Madurai, South India. The role of receptor proteins on midguts contributing to permissiveness of CHIKV to Aedes spp. mosquitoes was also undertaken. Mosquitoes were orally infected with CHIKV DRDE‐06. Infection of midguts and dissemination to heads was confirmed by immunofluorescence assay at different time points. A plaque assay was performed from mosquito homogenates at different time points to study CHIKV replication. Presence of putative CHIKV receptor proteins on mosquito midgut epithelial cells was detected by virus overlay protein binding assay (VOPBA). The identity of these proteins was established using mass spectrometry. CHIKV infection of Ae. aegypti and Ae. albopictus midguts and dissemination to heads was observed to be similar. A plaque assay performed with infected mosquito homogenates revealed that CHIKV replication dynamics was similar in Aedes sp. mosquitoes until 28 days post infection. VOPBA performed with mosquito midgut membrane proteins revealed that prohibitin could serve as a putative CHIKV receptor on Aedes mosquito midguts, whereas an absence of CHIKV binding protein/s on Culex quinquefasciatus midguts can partially explain the non‐permissiveness of these mosquitoes to infection.

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Increased Akt signaling in the mosquito fat body increases adult survivorship

Cited by 28 publications

References 48 publications

Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan

Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan

The role of lipid metabolism in aging, lifespan regulation, and age‐related disease

Understanding the mechanism of Chikungunya virus vector competence in three species of mosquitoes

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