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

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; Li, Chao; Wu, Kuan Wei; Shiao, Young‐Ji; Tsay, Huey Jen

doi:10.1016/j.neurobiolaging.2019.11.018

Cited by 37 publications

(19 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although APP23 mice do not model AD-related weight loss, their lower body weight at a pre-plaque stage corresponds to lower body weight of AD patients, which arises from early weight loss prior to the onset of clinical AD symptoms [ 16 , 22 ]. Consistent with literature, HSD induced a mild, but HFD a substantial body weight gain [ 19 , 23 – 25 ], in which APP23 mice gained less fat mass. Analysis of food intake as a potential mechanism for lower body weight revealed lower HFD consumption, contradicting a study in APP23 males reporting increased food intake [ 26 ].…”

Section: Discussionsupporting

confidence: 89%

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis

Schreyer

Berndt

Eckstein

et al. 2021

Aging

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife increases AD risk. Furthermore, AD is associated with diabetes-like alterations in glucose metabolism. Here, we investigated metabolic features of amyloid precursor protein overexpressing APP23 female mice modeling AD upon long-term challenge with high-sucrose (HSD) or high-fat diet (HFD). Compared to wild type littermates (WT), APP23 females were less prone to mild HSD-induced and considerable HFD-induced glucose tolerance deterioration, despite unaltered glucose tolerance during normal-control diet. Indirect calorimetry revealed increased energy expenditure and hyperactivity in APP23 females. Dietary interventions, especially HFD, had weaker effects on lean and fat mass gain, steatosis and adipocyte hypertrophy of APP23 than WT mice, as shown by 1 H-magnetic-resonance-spectroscopy, histological and biochemical analyses. Proteome analysis revealed differentially regulated expression of mitochondrial proteins in APP23 livers and brains. In conclusion, hyperactivity, increased metabolic rate, and global mitochondrial dysfunction potentially add up to the development of AD-related body weight changes in APP23 females, becoming especially evident during diet-induced metabolic challenge. These findings emphasize the importance of translating this metabolic phenotyping into human research to decode the metabolic component in AD pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 89%

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis

Schreyer

Berndt

Eckstein

et al. 2021

Aging

View full text Add to dashboard Cite

show abstract

“…We used a relevant model of glycemic index and demonstrated the expected significant differences in weight, cholesterol, glucose, and insulin levels consistent with what has been published previously for these experimental models [19,[63][64][65]. To our knowledge, the present study shows for the first time that the HGD has distinct differential effects on gene expression that are different from the LGD and characterized by up-regulation of differentially expressed protein-coding genes, transcription factors, as well as non-protein-coding genes (miRNAs, snoRNAs, and lncRNAs), that are involved in five major cellular pathways: neurodegenerative diseases (Alzheimer's disease), endothelial cell function (focal adhesion), cell signaling (PPAR signaling, PI3K-Akt signal- An additional finding of the two-factor analysis was that when the individual DEGs of the relevant pathways shown in Figure 10A (77 DEGs) were examined, it again became apparent that the sEHI reverted the gene expression profile of brain hippocampal microvascular endothelium of mice on the HGD to a profile similar to that of the LGD.…”

Section: Discussionsupporting

confidence: 78%

“…In rats, an HGD had detrimental effects on memory [15,16], disrupted hypothalamic redox homeostasis [17], and increased hippocampal endoplasmic reticulum stress [18]. In a mouse model of Alzheimer's disease, an HGD was found to increase neuroinflammation and cortical levels of Amyloid-β [19]. These studies suggest that an HGD is associated with cognitive impairment in animal models.…”

Section: Introductionmentioning

confidence: 91%

Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

et al. 2021

View full text Add to dashboard Cite

Diet is a modifiable risk factor for cardiovascular disease (CVD) and dementia, yet relatively little is known about the effect of a high glycemic diet (HGD) on the brain’s microvasculature. The objective of our study was to determine the molecular effects of an HGD on hippocampal microvessels and cognitive function and determine if a soluble epoxide hydrolase (sEH) inhibitor (sEHI), known to be vasculoprotective and anti-inflammatory, modulates these effects. Wild type male mice were fed a low glycemic diet (LGD, 12% sucrose/weight) or an HGD (34% sucrose/weight) with/without the sEHI, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), for 12 weeks. Brain hippocampal microvascular gene expression was assessed by microarray and data analyzed using a multi-omic approach for differential expression of protein and non-protein-coding genes, gene networks, functional pathways, and transcription factors. Global hippocampal microvascular gene expression was fundamentally different for mice fed the HGD vs. the LGD. The HGD response was characterized by differential expression of 608 genes involved in cell signaling, neurodegeneration, metabolism, and cell adhesion/inflammation/oxidation effects reversible by t-AUCB and hence sEH inhibitor correlated with protection against Alzheimer’s dementia. Ours is the first study to demonstrate that high dietary glycemia contributes to brain hippocampal microvascular inflammation through sEH.

show abstract

“…Consistent with these ideas, the administration of a high sugar diet in a mouse model of Alzheimer’s disease led to a significant increase in serum and brain amyloid levels (Yeh et al, 2019 ). More importantly, in a cross-sectional study in cognitively normal older adults, subjects on high glycemic carbohydrates and/or high sugar diets had higher cerebral amyloid deposition as measured by positron emission tomography (PET scan), and those subjects on a high sugar intake also performed worse on the Mini-Mental State Examination (Taylor et al, 2017 ).…”

Section: Fructose Metabolism and Alzheimer’s Diseasementioning

confidence: 89%

Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer’s Disease

Johnson

Gómez‐Pinilla

Nagel

et al. 2020

Front. Aging Neurosci.

View full text Add to dashboard Cite

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

Cited by 37 publications

References 62 publications

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis

Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer’s Disease

Contact Info

Product

Resources

About