Premium
Mid‐gestation low‐dose LPS administration results in excessive weight gain upon a Western Style Diet in female mouse offspring
Author(s) -
Plösch Torsten,
Dijkstra Dorieke J.,
Verkaik-Schakel Rikst Nynke,
Stojanovska Violeta,
Scherjon Sicco A.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03887
Subject(s) - offspring , endocrinology , medicine , leptin , gestation , in utero , weaning , adipose tissue , pregnancy , insulin , obesity , fetus , physiology , biology , genetics
Exposure to gestational complications can have a life‐long influence on the offspring’s health. Inflammation is observed in many complications, including preeclampsia and gestational diabetes mellitus, and is likely mediating the long‐term consequences for the offspring. Here we use a mouse model of LPS‐induced maternal inflammation to examine the consequences of gestational inflammation on offspring’s metabolic health. 25μg/kg LPS was administered to pregnant C57Bl6/J mice on gestational day 10. After weaning, all offspring was fed a semi‐synthetic control diet. At 12 weeks of age, half of the animals were switched to a Western‐Style Diet (WSD). Body composition (MRI) and glucose‐ and insulin tolerance were measured at 12 and 24 weeks of age. At 24 weeks of age, blood pressure was measured, and plasma, fat pads, liver and brain were collected and analyzed at the molecular level. Males and females were analyzed separately. LPS‐exposed female offspring showed an increase in body fat mass at 12 weeks of age, and the combination of LPS‐exposure and WSD markedly increased food intake, body weight and body fat mass in the females at 24 weeks of age. Observed changes in glucose‐and insulin tolerance, leptin and insulin levels and gene expression in liver, adipose tissue and hypothalamus were associated with body weight, not with in utero LPS exposure. In utero LPS exposure leads to increased intake of WSD in female offspring, which is likely causative of the observed increased body weight and fat mass and metabolic and molecular changes. A metabolic driver for increased food intake was not identified. Thus, in this model, gestational inflammation might lead to increased food intake through programmed behavioral traits rather that fetal programming of metabolism. Support or Funding Information This work was supported by ZonMw (91211053).