THE IMPACT AND MECHANISM OF N-3 PUFAS DEFICIENCY ON COGNITIVE FUNCTION IN DIABETIC MICE

LI Xiao-huan; MENG Hua-li; HUANG Xiao-li; WU Hao

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Acta Nutrimenta Sinica ›› 2025, Vol. 47 ›› Issue (2) : 149-156.

ORIGINAL ARTICLES

THE IMPACT AND MECHANISM OF N-3 PUFAS DEFICIENCY ON COGNITIVE FUNCTION IN DIABETIC MICE

LI Xiao-huan¹, MENG Hua-li¹, HUANG Xiao-li², WU Hao¹

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Abstract

Objective To investigate the impact of dietary n-3 PUFAs deficiency on diabetic cognitive function in mice and its underlying mechanisms. Methods 3-week-old male spontaneous diabetic KKay mice were randomly divided into two groups: the n-3 PUFAs normal group (normal n-3 PUFAs content diet, ND) and the n-3 PUFAs deficient group (n-3 PUFAs deficient diet, DD). Body weight and food intake were monitored weekly. One week before the end of this experiment, the fasting blood glucose detection and glucose tolerance tests were performed. Meanwhile, the cognitive function was assessed using the Y-maze and novel object recognition tests. After an 18-week intervention, all mice were euthanized to collect red blood cells, colonic contents and brain tissues. The relative contents of n-3 PUFAs in red blood cell membranes and brain tissues were determined by gas chromatography. The expression levels of oxidative stress-related proteins in the hippocampus were analyzed by Western blotting. Metagenomics and untargeted metabolomics were used to examine the gut microbiota and metabolites in the colonic contents. Results There were no significant differences in body weight and food intake between the ND and DD groups. Compared with the ND group, the DD group developed increased fasting blood glucose level and exacerbated glucose intolerance. The functional studies showed that n-3 PUFAs deficiency reduced the entries into the new arm, recognition index, discrimination ratio and discrimination score. n-3 PUFAs deficiency increased oxidative stress in the hippocampus. Interestingly, n-3 PUFAs deficiency did not lead to a decrease in the brain n-3 PUFAs level, despite the significant reduction in red blood cell membrane n-3 PUFAs level. Metagenomic and untargeted metabolomicanalyses showed significant alterations in the intestinal metabolic composition in the DD group compared to the ND group, with a decreased ratio of Firmicutes to Bacteroidetes. Significant alterations in the pathways of nutrition metabolism were demonstrated. Conclusion Dietary deficiency of n-3 PUFAs exacerbates cognitive dysfunction in diabetic mice possibly by disrupting gut microbiota homeostasis and altering the composition of metabolites.

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n-3 polyunsaturated fatty acids / diabetes / cognitive function / gut microbiota / mice

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LI Xiao-huan, MENG Hua-li, HUANG Xiao-li, WU Hao. THE IMPACT AND MECHANISM OF N-3 PUFAS DEFICIENCY ON COGNITIVE FUNCTION IN DIABETIC MICE[J]. Acta Nutrimenta Sinica. 2025, 47(2): 149-156

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