A high-sucrose diet aggravates Alzheimer's disease pathology, attenuates hypothalamic leptin signaling, and impairs food-anticipatory activity in APPswe/PS1dE9 mice

• Published in: Neurobiology of aging Vol. 90; pp. 60 - 74
• Main Authors: Yeh, Skye Hsin-Hsien, Shie, Feng-Shiun, Liu, Hui-Kang, Yao, Heng-Hsiang, Kao, Pei-Chen, Lee, Yi-Heng, Chen, Li-Min, Hsu, Shu-Meng, Chao, Li-Jung, Wu, Kuan-Wei, Shiao, Young-Ji, Tsay, Huey-Jen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2020
• Subjects: Alzheimer's disease; amyloid-β; High-sucrose diet; Hypothalamus; Leptin; Signal transducer and activator of transcription 3, STAT3; amyloid-β; Hypothalamus; Signal transducer and activator of transcription 3, STAT3; Alzheimer's disease; Leptin; High-sucrose diet
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2019.11.018

High-fat and high-sugar diets contribute to the prevalence of type 2 diabetes and Alzheimer's disease (AD). Although the impact of high-fat diets on AD pathogenesis has been established, the effect of high-sucrose diets (HSDs) on AD pathogenesis remains unclear. This study sought to determine the impact of HSDs on AD-related pathologies. Male APPswe/PS1dE9 (APP/PS1) transgenic and wild-type mice were provided with HSD and their cognitive and hypothalamus-related noncognitive parameters, including feeding behaviors and glycemic regulation, were compared. HSD-fed APP/PS1 mice showed increased neuroinflammation, as well as increased cortical and serum levels of amyloid-β. HSD-fed APP/PS1 mice showed aggravated obesity, hyperinsulinemia, insulin resistance, and leptin resistance, but there was no induction of hyperphagia or hyperleptinemia. Leptin-induced phosphorylation of signal transducer and activator of transcription 3 in the dorsomedial and ventromedial hypothalamus was reduced in HSD-fed APP/PS1 mice, which might be associated with attenuated food-anticipatory activity, glycemic dysregulation, and AD-related noncognitive symptoms. Our study demonstrates that HSD aggravates metabolic stresses, increases AD-related pathologies, and attenuates hypothalamic leptin signaling in APP/PS1 mice. [Display omitted] •HSD increased neuroinflammation and Aβ in APP/PS1 mice.•HSD aggravated insulin resistance in APP/PS1 mice without hyperphagia.•HSD increased weight gain and fat mass in WT and APP/PS1 mice.•HSD reduced leptin signaling in 2 hypothalamic nuclei of APP/PS1 mice.•HSD attenuated food-anticipatory activity in APP/PS1 mice.