Effects of pregnancy on obesity-induced inflammation in a mouse model of fetal programming

Objective Maternal obesity is associated with increased risk of metabolic dysfunction in the offspring. It is not clear whether it is the metabolic changes or chronic low-grade inflammation in the obese state that causes this metabolic programming. We therefore investigated whether low-grade inflammation was present in obese dams compared to controls dams at gestation day 18.

Methods Female mice were fed either a standard chow diet or a highly palatable obesogenic diet for 6 weeks prior to conception. Mice were either euthanized before mating (n=12 in each group), or euthanized on gestation day 18 (n=8 in each group). Blood and tissues were collected for analysis. Results The obesogenic diet increased body weight and decreased insulin sensitivity prior to conception, while there was no difference between the groups at gestation day 18.

Local inflammation was assayed by macrophage count in adipose tissue and liver. Macrophage count in the adipose tissue was increased significantly by the obesogenic diet, and the hepatic count also showed a tendency to increased macrophage infiltration prior to gestation. This was further supported by a decreased population of monocytes in the blood of the obese animals, which suggested that monocytes are being recruited from the blood to the liver and adipose tissue in the obese animals.

Gestation reversed macrophage infiltration, such that obese dams showed a lower adipose tissue macrophage count at the end of gestation compared to pre-pregnancy obese mice, and there were no longer a tendency towards increased hepatic macrophage count. Placental macrophage count was also similar in the two groups.

Conclusion At gestation day 18, obese dams were found to have similar macrophage infiltration in placenta, adipose tissue and liver as lean dams, despite an incipient infiltration before gestation. Thus, the obesity-induced inflammation was reversed during gestation.