In utero exposure to gestational diabetes mellitus conditions TLR4 and TLR2 activated IL-1beta responses in spleen cells from rat offspring

• How gestational diabetes affects the insulin sensitivity of the offspring are poorly understood.
• We show gestational diabetes mellitus increased interleukin-1β and -10 production by offspring spleen cells.
• Effects of gestational diabetes mellitus on interleukin-1β and -10 production were independent of postnatal diet.
• Our findings show that spleen cells from the offspring of gestational diabetes mellitus dams are highly immune reactive.

Fetal exposure to gestational diabetes mellitus (GDM) is associated with a higher risk of youth-onset insulin resistance and type 2 diabetes. We have previously shown that the rat offspring of GDM dams are insulin resistant when compared to the offspring of lean dams. Since inflammation influences insulin sensitivity, we examined the impact of fetal exposure to GDM on inflammatory responses in the offspring. In rats, we compared inflammatory activity in newborn pups as well as 16 week-old young-adult offspring from lean control dams with offspring from high fat and sucrose diet (HFS)-induced GDM dams. To determine whether there are additive effects of exposure to GDM and post-weaning diets, offspring of lean and GDM dams were fed either low fat or HFS diets until 16 weeks of age. Plasma levels of interleukin(IL)-1β were elevated in the offspring of GDM dams. To determine whether this was related to immune reactivity, spleen cells from both the newborn and 16 week-old offspring were isolated and reactivity to the toll-like receptor activators, pam3CSK4 and lipopolysaccharides were measured over a 72 h timeframe. Spleen cells of GDM dams exhibited sustained stimulation of interleukin(IL)-1β and IL-10 production, whereas IL-1β and IL-10 synthesis diminished over time in spleen cells from the offspring of lean dams. Additive effects of GDM exposure and post-weaning HFS diet were not observed, suggesting the effects of GDM on cytokine production are independent of the post-weaning diet. Thus, we conclude that exposure to GDM in utero may condition the immune reactivity of spleen cells.