510 - Maternal Diet-Induced Obesity Causes Increased Adiposity and Altered Metabolic Phenotype in C57Bl/6 Offspring Exposed to Early Postnatal LPS

Poster Number: 510
Publication Number: 510.238

Lauren Buckley, University of Minnesota Medical School, Minneapolis, MN, United States; Debra Kulhanek, University of Minnesota Medical School, minneapolis, MN, United States; Garima Singh, University of Minnesota Medical School, Minneapolis, MN, United States; Tate A. Gisslen, University of Minnesota, Edina, MN, United States; Megan E. Paulsen, University of Minnesota Medical School, Minneapolis, MN, United States

Background: Inflammatory stress during development is associated with long term metabolic health. Maternal diet-induced obesity (DIO) and neonatal sepsis are common inflammatory stressors occurring during perinatal development. The role of these combined stressors on the development of metabolic phenotype is poorly defined.

Objective:
Describe the metabolic phenotype in adult offspring exposed to inflammatory stress derived from maternal diet and neonatal sepsis.

Design/Methods: C57B1/6 dams (n=20) were randomized to high-fat, high-sugar (DIO) or control (CON) diet. Offspring (n=36, F:50%) were injected with lipopolysaccharide (LPS, 1 µg/g) or saline on postnatal day 7 to create 4 groups of offspring (CON-SAL, CON-LPS, DIO-SAL, DIO-LPS). Offspring body composition, meal pattern analysis, energy expenditure, and activity were measured at 4 months by metabolic chambers. Dam hormone/lipid analysis was measured by ELISA. Group differences were analyzed by two-way ANOVA. Pearson correlation coefficient (r) was used to measure linear correlation. P-values < 0.05 were significant.

Results: Exposure to maternal DIO or early postnatal LPS alone did not affect adult offspring weight or body composition. There was a significant interaction between the effect of maternal diet and early LPS on adult offspring adiposity (p=0.02, F(1,30)=6.530). Offspring exposed to maternal CON diet and LPS (CON-LPS) had 30% lower %fat mass compared to CON-SAL. Offspring exposed to maternal DIO and LPS (DIO-LPS) had 29% higher fat mass compared to DIO-SAL. There was no difference in energy intake or expenditure between offspring groups. In secondary analyses, there were no differences between male offspring groups in meal pattern. Maternal diet accounted for 46% and 54% of the total variance of female offspring meal frequency and size, respectively (F(1,14)=12.45, p< 0.01; F(1,14)=18.48, p< 0.01)) with 19% higher meal frequency and 22% lower meal size in offspring exposed to maternal obesity. In offspring exposed to LPS, maternal cholesterol (r=0.50, p=0.048), insulin (r=0.70, p< 0.01), and total energy consumption (r=0.62, p< 0.01) were positively correlated with offspring %fat mass.Conclusion(s): Early postnatal LPS triggers increased adiposity in offspring exposed to maternal DIO. Type of inflammatory stress, timing of exposure during development and biologic sex are important variables in understanding the role of inflammatory stress in the developmental origins of obesity.