Mid-gestation low-dose LPS administration results in female-specific excessive weight gain upon a western style diet...

Area of Science:

• Reproductive biology
• Developmental biology
• Metabolic health

Background:

• Gestational complications like preeclampsia and gestational diabetes are linked to long-term adverse health outcomes in offspring.
• A low-grade systemic inflammatory response is a potential mediator of these long-term effects.
• Understanding the impact of gestational inflammation on offspring's adult health is crucial.

Purpose of the Study:

• To investigate the long-term consequences of lipopolysaccharide (LPS)-induced gestational inflammation on offspring's metabolic and cardiovascular health in adulthood.
• To explore the role of maternal oxidative stress in mediating these effects.
• To examine the combined impact of prenatal inflammation and postnatal diet on offspring's health.

Main Methods:

• Pregnant C57Bl/6J mice were administered LPS on gestational day 10.5.
• Maternal plasma metabolomics was used to assess oxidative stress.
• Offspring were fed a control or Western-style diet (WSD) from 12 to 24 weeks of age.
• Offspring's body weight, body fat mass, glucose tolerance, and hormonal levels (leptin, insulin) were measured.
• Gene expression in the liver, adipose tissue, and hypothalamus was analyzed.

Main Results:

• LPS administration induced maternal oxidative stress, persisting for at least 5 days.
• Female offspring exposed to both LPS and WSD exhibited hyperphagia, increased body weight, and elevated body fat mass.
• Significant alterations in glucose tolerance, leptin, and insulin levels were observed in these offspring.
• Changes in gene expression related to metabolic regulation in the liver and adipose tissue were noted.
• Hypothalamic gene expression involved in food intake regulation showed subtle alterations.

Conclusions:

• Gestational inflammation, mediated by oxidative stress, can program offspring for long-term metabolic dysfunction.
• The combination of prenatal inflammatory insults and a Western diet exacerbates adverse metabolic outcomes in female offspring.
• Dysregulation of hypothalamic signaling may contribute to altered feeding behavior and obesity in affected offspring.
• These findings highlight the critical role of the maternal inflammatory environment in shaping offspring's lifelong health trajectory.