18F-Fluorodeoxyglucose positron emission tomography/computed tomography imaging reveals the protective effect of docosahexaenoic acid on glucose metabolism by reducing brain 27-hydroxycholesterol

• Published in: Experimental gerontology Vol. 196; p. 112577
• Main Authors: Zhang, Dalong, Wang, Zehao, Guo, Shuangshuang, Sun, Yue, Zhou, Dezheng, Li, Wen, Yan, Jing, Chen, Yongjie, Luo, Suhui, Huang, Guowei, Qian, Zhiyong, Li, Zhenshu
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 15.10.2024; Elsevier
• Subjects: 18F-FDG-PET-CT; 27-hydroxycholesterol; Cholesterol; Docosahexaenoic acid; Glucose metabolism; SAMP8 mouse; GC–MS; LDL-C; SAMP8 mouse; HMG-CoA; 18F-FDG; Docosahexaenoic acid; 27-OHC; CMRglc; Cholesterol; TC; HDL-C; Glucose metabolism; SUVglc; 18F-FDG-PET-CT; DHA; 27-hydroxycholesterol; ELISA
• ISSN: 0531-5565; 1873-6815; 1873-6815
• DOI: 10.1016/j.exger.2024.112577

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice. •Supplementation of docosahexaenoic acid can improve brain glucose metabolism.•Supplementation of docosahexaenoic acid can optimize the structure of cholesterol.•27-Hydroxycholesterol is negatively correlated with glucose metabolism in brain.