Docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high-fat diet
Introduction: Diminished brain insulin sensitivity is associated with reduced cognitive function. Docosahexaenoic acid (DHA) is known to maintain normal brain function. Objectives: This study aimed to determine whether DHA impacts hippocampal insulin sensitivity and cognitive function in aged rats f...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
|
| Series: | Journal of Advanced Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123222001114 |
| _version_ | 1797894427976400896 |
|---|---|
| author | Jiqu Xu Ben Ni Congcong Ma Shuang Rong Hui Gao Li Zhang Xia Xiang Qingde Huang Qianchun Deng Fenghong Huang |
| author_facet | Jiqu Xu Ben Ni Congcong Ma Shuang Rong Hui Gao Li Zhang Xia Xiang Qingde Huang Qianchun Deng Fenghong Huang |
| author_sort | Jiqu Xu |
| collection | DOAJ |
| description | Introduction: Diminished brain insulin sensitivity is associated with reduced cognitive function. Docosahexaenoic acid (DHA) is known to maintain normal brain function. Objectives: This study aimed to determine whether DHA impacts hippocampal insulin sensitivity and cognitive function in aged rats fed a high-fat diet (HFD). Methods: Eight-month-old female Sprague-Dawley rats were randomly divided into three groups (n = 50 each). Rats in the aged group, HFD group, and DHA treatment group received standard diet (10 kcal% fat), HFD (45 kcal% fat), and DHA-enriched HFD (45 kcal% fat, 1% DHA, W/W) for 10 months, respectively. Four-month-old female rats (n = 40) that received a standard diet served as young controls. Neuroinflammation, oxidative stress, amyloid formation, and tau phosphorylation in the hippocampus, as well as systemic glucose homeostasis and cognitive function, were tested. Results: DHA treatment relieved a block in the insulin signaling pathway and consequently protected aged rats against HFD-induced hippocampal insulin resistance. The beneficial effects were explained by a DHA-induced decrease in systemic glucose homeostasis dysregulation, hippocampal neuroinflammation and oxidative stress. In addition, DHA treatment broke the reciprocal cycle of hippocampal insulin resistance, Aβ burden, and tau hyperphosphorylation. Importantly, treatment of model rats with DHA significantly increased their cognitive capacity, as evidenced by their increased hippocampal-dependent learning and memory, restored neuron morphology, enhanced cholinergic activity, and activated cyclic AMP-response element-binding protein. Conclusion: DHA improves cognitive function by enhancing hippocampal insulin sensitivity. |
| first_indexed | 2024-04-10T07:08:53Z |
| format | Article |
| id | doaj.art-e008f3ecdfe84a20b676f753b855cfd0 |
| institution | Directory Open Access Journal |
| issn | 2090-1232 |
| language | English |
| last_indexed | 2024-04-10T07:08:53Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj.art-e008f3ecdfe84a20b676f753b855cfd02023-02-27T04:07:03ZengElsevierJournal of Advanced Research2090-12322023-03-01453142Docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high-fat dietJiqu Xu0Ben Ni1Congcong Ma2Shuang Rong3Hui Gao4Li Zhang5Xia Xiang6Qingde Huang7Qianchun Deng8Fenghong Huang9Department of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. China; Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. ChinaDepartment of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. China; Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. ChinaDepartment of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. China; Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. ChinaDepartment of Nutrition and Food Hygiene, School of Public Health, Wuhan University of Science and Technology, Wuhan 430065, P.R. ChinaDepartment of Clinical Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, P.R. ChinaDepartment of Neurology, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, No. 11, Lingjiaohu Road, Wuhan 430015, P.R. ChinaDepartment of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. China; Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. ChinaDepartment of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. China; Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. ChinaDepartment of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. China; Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. ChinaDepartment of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. China; Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. China; Corresponding author at: Department of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, 2 Xudong Second Road, Wuhan 430062, P.R. China..Introduction: Diminished brain insulin sensitivity is associated with reduced cognitive function. Docosahexaenoic acid (DHA) is known to maintain normal brain function. Objectives: This study aimed to determine whether DHA impacts hippocampal insulin sensitivity and cognitive function in aged rats fed a high-fat diet (HFD). Methods: Eight-month-old female Sprague-Dawley rats were randomly divided into three groups (n = 50 each). Rats in the aged group, HFD group, and DHA treatment group received standard diet (10 kcal% fat), HFD (45 kcal% fat), and DHA-enriched HFD (45 kcal% fat, 1% DHA, W/W) for 10 months, respectively. Four-month-old female rats (n = 40) that received a standard diet served as young controls. Neuroinflammation, oxidative stress, amyloid formation, and tau phosphorylation in the hippocampus, as well as systemic glucose homeostasis and cognitive function, were tested. Results: DHA treatment relieved a block in the insulin signaling pathway and consequently protected aged rats against HFD-induced hippocampal insulin resistance. The beneficial effects were explained by a DHA-induced decrease in systemic glucose homeostasis dysregulation, hippocampal neuroinflammation and oxidative stress. In addition, DHA treatment broke the reciprocal cycle of hippocampal insulin resistance, Aβ burden, and tau hyperphosphorylation. Importantly, treatment of model rats with DHA significantly increased their cognitive capacity, as evidenced by their increased hippocampal-dependent learning and memory, restored neuron morphology, enhanced cholinergic activity, and activated cyclic AMP-response element-binding protein. Conclusion: DHA improves cognitive function by enhancing hippocampal insulin sensitivity.http://www.sciencedirect.com/science/article/pii/S2090123222001114Docosahexaenoic acidHippocampusInsulin resistanceCognitive functionHigh-fat dietAging |
| spellingShingle | Jiqu Xu Ben Ni Congcong Ma Shuang Rong Hui Gao Li Zhang Xia Xiang Qingde Huang Qianchun Deng Fenghong Huang Docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high-fat diet Journal of Advanced Research Docosahexaenoic acid Hippocampus Insulin resistance Cognitive function High-fat diet Aging |
| title | Docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high-fat diet |
| title_full | Docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high-fat diet |
| title_fullStr | Docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high-fat diet |
| title_full_unstemmed | Docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high-fat diet |
| title_short | Docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high-fat diet |
| title_sort | docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high fat diet |
| topic | Docosahexaenoic acid Hippocampus Insulin resistance Cognitive function High-fat diet Aging |
| url | http://www.sciencedirect.com/science/article/pii/S2090123222001114 |
| work_keys_str_mv | AT jiquxu docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet AT benni docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet AT congcongma docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet AT shuangrong docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet AT huigao docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet AT lizhang docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet AT xiaxiang docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet AT qingdehuang docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet AT qianchundeng docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet AT fenghonghuang docosahexaenoicacidenhanceshippocampalinsulinsensitivitytopromotecognitivefunctionofagedratsonahighfatdiet |