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

Skye Hsin Hsien Yeh; Feng Shiun Shie; Hui Kang Liu; Heng Hsiang Yao; Pei Chen Kao; Yi Heng Lee; Li Min Chen; Shu Meng Hsu; Li Jung Chao; Kuan Wei Wu; Young Ji Shiao; Huey Jen Tsay

doi:10.1016/j.neurobiolaging.2019.11.018

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

Skye Hsin Hsien Yeh, Feng Shiun Shie, Hui Kang Liu, Heng Hsiang Yao, Pei Chen Kao, Yi Heng Lee, Li Min Chen, Shu Meng Hsu, Li Jung Chao, Kuan Wei Wu, Young Ji Shiao^*, Huey Jen Tsay

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	60-74
Number of pages	15
Journal	Neurobiology of Aging
Volume	90
DOIs	https://doi.org/10.1016/j.neurobiolaging.2019.11.018
State	Published - Jun 2020

Keywords

Alzheimer's disease
amyloid-β
High-sucrose diet
Hypothalamus
Leptin
Signal transducer and activator of transcription 3, STAT3

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.neurobiolaging.2019.11.018

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Yeh, S. H. H., Shie, F. S., Liu, H. K., Yao, H. H., Kao, P. C., Lee, Y. H., Chen, L. M., Hsu, S. M., Chao, L. J., Wu, K. W., Shiao, Y. J., & Tsay, H. J. (2020). A high-sucrose diet aggravates Alzheimer's disease pathology, attenuates hypothalamic leptin signaling, and impairs food-anticipatory activity in APPswe/PS1dE9 mice. Neurobiology of Aging, 90, 60-74. https://doi.org/10.1016/j.neurobiolaging.2019.11.018

@article{85239887c2b14a9a8334b946dabd9abc,

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

abstract = "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.",

keywords = "Alzheimer's disease, amyloid-β, High-sucrose diet, Hypothalamus, Leptin, Signal transducer and activator of transcription 3, STAT3",

author = "Yeh, {Skye Hsin Hsien} and Shie, {Feng Shiun} and Liu, {Hui Kang} and Yao, {Heng Hsiang} and Kao, {Pei Chen} and Lee, {Yi Heng} and Chen, {Li Min} and Hsu, {Shu Meng} and Chao, {Li Jung} and Wu, {Kuan Wei} and Shiao, {Young Ji} and Tsay, {Huey Jen}",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2020",

month = jun,

doi = "10.1016/j.neurobiolaging.2019.11.018",

language = "English",

volume = "90",

pages = "60--74",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

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Yeh, SHH, Shie, FS, Liu, HK, Yao, HH, Kao, PC, Lee, YH, Chen, LM, Hsu, SM, Chao, LJ, Wu, KW, Shiao, YJ & Tsay, HJ 2020, 'A high-sucrose diet aggravates Alzheimer's disease pathology, attenuates hypothalamic leptin signaling, and impairs food-anticipatory activity in APPswe/PS1dE9 mice', Neurobiology of Aging, vol. 90, pp. 60-74. https://doi.org/10.1016/j.neurobiolaging.2019.11.018

TY - JOUR

T1 - A high-sucrose diet aggravates Alzheimer's disease pathology, attenuates hypothalamic leptin signaling, and impairs food-anticipatory activity in APPswe/PS1dE9 mice

AU - Yeh, Skye Hsin Hsien

AU - Shie, Feng Shiun

AU - Liu, Hui Kang

AU - Yao, Heng Hsiang

AU - Kao, Pei Chen

AU - Lee, Yi Heng

AU - Chen, Li Min

AU - Hsu, Shu Meng

AU - Chao, Li Jung

AU - Wu, Kuan Wei

AU - Shiao, Young Ji

AU - Tsay, Huey Jen

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - amyloid-β

KW - High-sucrose diet

KW - Hypothalamus

KW - Leptin

KW - Signal transducer and activator of transcription 3, STAT3

UR - http://www.scopus.com/inward/record.url?scp=85076853405&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2019.11.018

DO - 10.1016/j.neurobiolaging.2019.11.018

M3 - Article

C2 - 31879131

AN - SCOPUS:85076853405

SN - 0197-4580

VL - 90

SP - 60

EP - 74

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

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

Abstract

Keywords

UN SDGs

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