Western diet consumption by host vertebrate promotes altered gene expression on Aedes aegypti reducing its lifespan and increasing fertility following blood feeding

Abstract

Background: The high prevalence of metabolic syndrome in low- and middle-income countries is linked to an increase in Western diet consumption, characterized by a high intake of processed foods, which impacts the levels of blood sugar and lipids, hormones, and cytokines. Hematophagous insect vectors, such as the yellow fever mosquito Aedes aegypti, rely on blood meals for reproduction and development and are therefore exposed to the components of blood plasma. However, the impact of the alteration of blood composition due to malnutrition and metabolic conditions on mosquito biology remains understudied.

Methods: In this study, we investigated the impact of whole-blood alterations resulting from a Western-type diet on the biology of Ae. aegypti. We kept C57Bl6/J mice on a high-fat, high-sucrose (HFHS) diet for 20 weeks and followed biological parameters, including plasma insulin and lipid levels, insulin tolerance, and weight gain, to validate the development of metabolic syndrome. We further allowed Ae. aegypti mosquitoes to feed on mice and tracked how altered host blood composition modulated parameters of vector capacity.

Results: Our findings identified that HFHS-fed mice resulted in reduced mosquito longevity and increased fecundity upon mosquito feeding, which correlated with alteration in the gene expression profile of nutrient sensing and physiological and metabolic markers as studied up to several days after blood ingestion.

Conclusions: Our study provides new insights into the overall effect of alterations of blood components on mosquito biology and its implications for the transmission of infectious diseases in conditions where the frequency of Western diet-induced metabolic syndromes is becoming more frequent. These findings highlight the importance of addressing metabolic health to further understand the spread of mosquito-borne illnesses in endemic areas.

Keywords: Aedes aegypti; Blood feeding; Immunometabolism; Malnutrition; Metabolic syndrome; Vector capacity; Vector competence; Western diet.

Fig. 1

A 20-week HSHF dietary intervention induced metabolic syndrome symptoms in C57 mice. Mice were fed with either a CHOW or an HSHF diet for 20 weeks. Over the course of the experiment, A weight gain was monitored weekly, while B insulin and C glucose tolerance were evaluated in the 19th and 20th weeks, respectively. By the end of the dietary intervention, blood was collected, and D insulin, E glucose, F triglycerides, G total cholesterol, and H AST/ALT levels were measured. At least six mice were used in each experiment (A–H). Unpaired t-test was performed. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001

Fig. 2

Mosquitoes fed on an HFHS mouse had a reduced survival rate. Mice were fed with either a CHOW or an HSHF diet for 20 weeks. Over the course of the experiment, metabolic syndrome was followed by tracking weight gain, glucose, and insulin sensitivity. Then, Aedes mosquitoes were allowed to feed on anesthetized mice, and A daily survival was measured over the course of 30 days. Alternatively, whole-body relative expression levels of B TOR, C insulin receptor, and D FoxO was measured by qRT-PCR 1 and 4 days pbm. Four biological replicates were prepared using independent mosquito hatches and dietary protocols. Sugar-fed (SF) mosquitoes were used as a baseline for survival and gene expression. A Mantel-Cox test and B–D one-way ANOVA followed by Tukey’s multiple comparison tests were performed. ns: non-significant, *P < 0.05, ***P < 0.001

Fig. 3

Mosquitoes fed on an HFHS mouse had an increased oviposition and lipid uptake. Mice were fed with either a CHOW or an HSHF diet for 20 weeks. Over the course of the experiment, metabolic syndrome was followed by tracking weight gain, glucose, and insulin sensitivity. Aedes aegypti mosquitoes were allowed to feed on anesthetized mice, and A egg layering was measured at 5 days pbm. Following a blood meal, mosquitoes were dissected, and TAG content was measured in the B fat body and C ovaries at 2 and 3 days pbm, respectively. Whole-body relative expression levels of D lipophorin and E vitellogenin were measured by qRT-PCR 1 and 4 days pbm. Sugar-fed (SF) mosquitoes were used as a baseline for gene expression. Four biological replicates were prepared using independent mosquito hatches and dietary protocols. A–C Unpaired t-test was performed and D–E one-way ANOVA followed by Tukey’s multiple comparison tests were performed. ns: non-significant, *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 4

Mosquitoes fed on an HFHS mouse display a discrete regulation of metabolic markers and nutrient-sensing regulators. Mice were fed with either a CHOW or an HFHS diet for 20 weeks. Over the course of the experiment, metabolic syndrome was followed by tracking weight gain, glucose, and insulin sensitivity. Then, mosquitoes were allowed to feed on anesthetized mice, and whole-body relative expression levels of A Keren, B Vein, C STAT, D Domeless, E PIAS, F JNK-AAEL008622, G JNK-AAEL008634, H Kayak, and I caspase 16 were measured by qRT-PCR 1 and 4 days pbm. Sugar-fed (SF) mosquitoes were used as a baseline for gene expression. Four biological replicates were prepared using independent mosquito hatches and dietary protocols. A–I One-way ANOVA followed by Tukey’s multiple comparison tests was performed. ns: non-significant, P < 0.05, **P < 0.01, ***P < 0.001