Prenatal viral exposure followed by adult stress produces glucose intolerance in a mouse model

Abstract

Aims/hypothesis It has been suggested that the uterine environment may influence metabolic disease occurring later in adult life, and that adult stress may promote disease outcome. Using a mouse model, we tested whether in utero exposure to Ljungan virus (LV) followed by adult exposure to stress produces diabetes. The influence of the timing of viral exposure over the course of pregnancy was also tested. Materials and methods Pregnant CD-1 mice were exposed i.p. to LV on pregnancy days 4, 8, 12 or 17. Adult male mice from these pregnancies were stressed by being kept in shared cages. Stress only, LV exposure in utero only, and no-stress/no virus exposure groups were also followed.Outcome variables included bodyweight, epididymal fat weight, baseline glucose, glucose tolerance tests (60 and 120 min) and serum insulin. Results We demonstrated that male mice developed a type 2-like diabetes, including obesity, as adults if infected during pregnancy with LV. Diabetes at the age of 11 weeks was more severe in mice whose mothers were infected earlier than in those whose mothers were infected later in pregnancy. Only animals infected in utero and kept under stress developed diabetes; infection or stress alone did not cause disease. Conclusions/interpretation This work demonstrates that a type 2 diabetes-like disease can be virus-induced in a mouse model. Early in utero viral insults can set the stage for disease occurring during adult life, but the final manifestation of diabetes is dependent on the combination of early viral exposure and stress in adult life.

Long-term pathological consequences of prenatal infection: beyond brain disorders

“…Similar results were obtained in a mouse model, in which pregnant mice were infected with Ljungan virus (LV), a virus that belongs to the Picornavirus family and is virulent for laboratory rodents (126). Maternal LV exposure in mice has been shown to predispose the offspring to signs of Type 2 diabetes and obesity (110). These effects, however, were particularly manifest in LV-exposed mice that experienced additional stress during adolescence, suggesting that the severity of metabolic abnormalities following prenatal immune activation can be exacerbated by exposure to other environmental adversities, such as adolescent stress (110).…”

“…Maternal LV exposure in mice has been shown to predispose the offspring to signs of Type 2 diabetes and obesity (110). These effects, however, were particularly manifest in LV-exposed mice that experienced additional stress during adolescence, suggesting that the severity of metabolic abnormalities following prenatal immune activation can be exacerbated by exposure to other environmental adversities, such as adolescent stress (110). These findings are particularly relevant for the multifactorial etiology of obesity and Type 2 diabetes, which are likely caused by a combination of environmental (and genetic) factors (38,81).…”

Pancreatic islets of bank vole show signs of dysfunction after prolonged exposure to high glucose concentrations in vitro

“…However, its possible role in the development of diabetes in the bank voles remains to be proven. It has been shown in CD-1 mice that when the mother is inoculated with the Ljungan virus during gestation the offspring develops diabetes (Niklasson et al 2006).…”

Suppression of bank vole pancreatic islet function by proinflammatory cytokines

“…Its possible role in the development of diabetes in the bank voles remain to be proven. It has been shown that the CD1 mouse offspring develop diabetes when the mother is inoculated with the Ljungan virus during gestation (Niklasson et al, 2006).…”