The Effects of Maternal High Fat Diet on Behavioral Measures in C57BL/6J and BTBR T+ Itpr3tf/J Offspring.

Background:  The etiology for most cases of autism spectrum disorder (ASD) is unknown at this time. There is strong evidence for the genetic role in ASD but environmental factors also have a modifying role. One potential environmental factor is the maternal diet during pregnancy. Obesity before and during prenatal development increases the vulnerability of affective disorders including schizophrenia and ASD. Prenatal maternal obesity has been shown to be a risk factor for ASD and other developmental disabilities (Krakowiak et al. Pediatrics 2012;129;e1121),

Objectives: The objective of these experiments was to determine if a maternal high fat diet increases autistic-like behaviors in the offspring. A commonly used inbred mouse strain, C57BL/6J and a mouse model of ASD, the BTBR T⁺ Itpr3^tf/J (BTBR) were used.

Methods: Female mice were placed on either a high fat diet (60 kcal% fat D12492, Research Diets Inc, NJ) or a control diet (45 kcal% fat D12451, Research Diets Inc, NJ) for 2 weeks and then mated. The dams remained on the diet through weaning and then were placed on regular mouse chow. Both male and female offspring were behaviorally phenotyped as adults. One female and male per litter were used in up to four tests, each test at least 2 days apart.

Results: Preliminary data suggests that the prenatal high fat diet lowered the sociability in male C57BL/6J mice and to a lesser extent in the female C57BL/6J mice as well. The trend was the opposite in the BTBR mice where the controls were less social than the mice prenatally exposed to the high fat diet. The high fat diet did not have affect anxiety-like behavior the BTBR mice and the C57BL/6J male mice, but increased anxiety-like behavior in the C57BL/6J female mice. The high fat diet did not affect anxiety-like behavior, motor behavior, or exploratory behavior in the offspring.

Conclusions: Maternal obesity is a risk factor for ASD and the preliminary data demonstrated changes in social behavior and anxiety-like behavior that was both strain and sex dependent.