Mice born to mothers fed a diet high in omega-6 fatty acids and low in omega-3 fatty acids during pregnancy exhibit various behavioral changes including impaired social behaviors and enhanced recognition memory

Nobuyuki Sakayori; Kazuki Fujii; Masanori Katakura; Mayumi Adachi; Yumie Koshidaka; Keizo Takao; Makoto Sugita

doi:10.1016/j.tjnut.2024.12.031

Mice born to mothers fed a diet high in omega-6 fatty acids and low in omega-3 fatty acids during pregnancy exhibit various behavioral changes including impaired social behaviors and enhanced recognition memory

J Nutr. 2025 Jan 2:S0022-3166(24)01258-6. doi: 10.1016/j.tjnut.2024.12.031. Online ahead of print.

Authors

Nobuyuki Sakayori¹, Kazuki Fujii², Masanori Katakura³, Mayumi Adachi⁴, Yumie Koshidaka⁴, Keizo Takao², Makoto Sugita⁵

Affiliations

¹ Department of Physiology and Oral Physiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan. Electronic address: [email protected].
² Department of Behavioral Physiology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan; Life Science Research Center, University of Toyama, Toyama 930-0194, Japan; Research Center for Idling Brain Science, University of Toyama, Toyama 930-0194, Japan.
³ Laboratory of Nutritional Physiology, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
⁴ Life Science Research Center, University of Toyama, Toyama 930-0194, Japan.
⁵ Department of Physiology and Oral Physiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.

PMID: 39755239
DOI: 10.1016/j.tjnut.2024.12.031

Abstract

Background: Modern dietary trends have led to an increase in foods that are relatively high in n-6 polyunsaturated fatty acids (PUFAs) and low in n-3 PUFAs. We previously reported that the offspring of mother mice that consumed a diet high in n-6 linoleic acid (LA) and low in n-3 α-linolenic acid (ALA), hereinafter called the LA^high/ALA^low diet, exhibit behavioral abnormalities related to anxiety and feeding.

Objective: We currently lack a comprehensive overview of the behavioral abnormalities in these offspring, which was investigated in this study.

Methods: C57BL/6J virgin female mice at 11 weeks of age were fed either a control diet or the LA^high/ALA^low diet, mated at 13 weeks of age, and maintained on their respective diet throughout gestation. At birth, the lactating mothers' diet was replaced with standard lab chow. After weaning, the offspring continued to receive standard lab chow, and both male and female offspring at 1-63 weeks of age were analyzed using a comprehensive behavioral test battery (n = 6-14 offspring/group and offspring in each group were derived from at least 3 independent litters).

Results: Both male and female offspring exposed in utero to the LA^high/ALA^low diet exhibited impaired social behaviors including the lower number of contacts with novel mice in the social interaction test (diet, F_(1,15) = 9.807, P = 0.007, two-way analysis of variance (ANOVA)) and also showed enhanced recognition memory in the object location test (diet, F_(1,36) = 6.779, P = 0.013, two-way ANOVA) compared to offspring exposed in utero to the control diet. In addition, compared to sex-matched controls, female offspring displayed hyperactivity in the open field test (F_(1,36) = 6.097, P = 0.018, simple main effect analysis).

Conclusions: The maternal balance between dietary n-6 and n-3 PUFAs during pregnancy can have significant effects on the offspring's behaviors, lasting well into adulthood.

Keywords: arachidonic acid; brain; development; docosahexaenoic acid; docosapentaenoic acid; essential fatty acids; fear memory; motor coordination; prenatal; preterm.