TY - JOUR
T1 - Increased Akt signaling in the fat body of Anopheles stephensi extends lifespan and increases lifetime fecundity through modulation of insulin-like peptides
AU - Hun, Lewis V.
AU - Luckhart, Shirley
AU - Riehle, Michael A.
N1 - Funding Information: This work was supported by the National Institutes of Health (Grant numbers R21AI1225823 , R56AI118926 and R56AI129420 ). Publisher Copyright: © 2019 Elsevier Ltd
PY - 2019/10
Y1 - 2019/10
N2 - Insulin-like peptides (ILPs) and the insulin/insulin-like growth factor 1 signaling (IIS) cascade regulate numerous physiological functions, including lifespan, reproduction, immunity, and metabolism, in diverse eukaryotes. We previously demonstrated that in female Anopheles stephensi and Aedes aegypti mosquitoes, activation of the IIS cascade in the fat body led to a significant increase in lifespan. In this work, we elucidated two putative mechanisms in A. stephensi behind the observed lifespan extension and assessed whether this lifespan extension confers an overall fitness advantage to the mosquito. Specifically, we demonstrated that increased Akt signaling in the mosquito fat body following a blood meal significantly suppressed the expression of ILP2 in the head. Moreover, overexpression of active Akt in the fat body altered the expression of a putative insulin binding protein ortholog, Imaginal morphogenesis protein-Late 2 (Imp-L2), in response to transgene expression. Combined, these two factors may act to reduce overall levels of circulating ILP2 or other ILPs in the mosquito, in turn conferring increased survival. We also examined the impact increased fat body IIS had on lifetime fecundity and demonstrated that transgenic female mosquito populations had higher lifetime fecundity relative to non-transgenic sibling controls. These studies provide new insights into the complex hormonal and molecular mechanisms regulating the interplay between IIS, aging, and reproduction in this important vector of human malaria parasites.
AB - Insulin-like peptides (ILPs) and the insulin/insulin-like growth factor 1 signaling (IIS) cascade regulate numerous physiological functions, including lifespan, reproduction, immunity, and metabolism, in diverse eukaryotes. We previously demonstrated that in female Anopheles stephensi and Aedes aegypti mosquitoes, activation of the IIS cascade in the fat body led to a significant increase in lifespan. In this work, we elucidated two putative mechanisms in A. stephensi behind the observed lifespan extension and assessed whether this lifespan extension confers an overall fitness advantage to the mosquito. Specifically, we demonstrated that increased Akt signaling in the mosquito fat body following a blood meal significantly suppressed the expression of ILP2 in the head. Moreover, overexpression of active Akt in the fat body altered the expression of a putative insulin binding protein ortholog, Imaginal morphogenesis protein-Late 2 (Imp-L2), in response to transgene expression. Combined, these two factors may act to reduce overall levels of circulating ILP2 or other ILPs in the mosquito, in turn conferring increased survival. We also examined the impact increased fat body IIS had on lifetime fecundity and demonstrated that transgenic female mosquito populations had higher lifetime fecundity relative to non-transgenic sibling controls. These studies provide new insights into the complex hormonal and molecular mechanisms regulating the interplay between IIS, aging, and reproduction in this important vector of human malaria parasites.
KW - Imaginal morphogenesis protein-Late 2
KW - Imp-L2
KW - Insulin binding protein
KW - Insulin signaling
KW - Insulin-like peptide
KW - Mosquito
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U2 - 10.1016/j.jinsphys.2019.103932
DO - 10.1016/j.jinsphys.2019.103932
M3 - Article
C2 - 31445957
SN - 0022-1910
VL - 118
JO - Journal of insect physiology
JF - Journal of insect physiology
M1 - 103932
ER -