The Protective Effects of Acer okamotoanum and Isoquercitrin on Obesity and Amyloidosis in a Mouse Model.

Ji Hyun Kim,Eun Ju Cho,Sanghyun Lee

doi:10.3390/nu12051353

Abstract

Obesity increases risk of Alzheimer’s Disease (AD). A high fat diet (HFD) can lead to amyloidosis and amyloid beta (Aβ) accumulation, which are hallmarks of AD. In this study, protective effects of the ethyl acetate fraction of Acer okamotoanum (EAO) and isoquercitrin were evaluated on obesity and amyloidosis in the HFD- and Aβ-induced mouse model. To induce obesity and AD by HFD and Aβ, mice were provided with HFD for 10 weeks and were intracerebroventricularly injected with Aβ25–35. For four weeks, 100 and 10 mg/kg/day of EAO and isoquercitrin, respectively, were administered orally. Administration of EAO and isoquercitrin significantly decreased body weight in HFD and Aβ-injected mice. Additionally, EAO- and isoquercitrin-administered groups attenuated abnormal adipokines release via a decrease in leptin and an increase in adiponectin levels compared with the control group. Furthermore, HFD and Aβ-injected mice had damaged liver tissues, but EAO- and isoquercitrin-administered groups attenuated liver damage. Moreover, administration of EAO and isoquercitrin groups down-regulated amyloidosis-related proteins in the brain such as β-secretase, presenilin (PS)-1 and PS-2 compared with HFD and Aβ-injected mice. This study indicated that EAO and isoquercitrin attenuated HFD and Aβ-induced obesity and amyloidosis, suggesting that they could be effective in preventing and treating both obesity and AD.

Highlights

For many years obesity has been a worldwide public health problem
Administration of ethyl acetate fraction of Acer okamotoanum (EAO), isoquercitrin, donepezil, and conjugated linoleic acid (CLA) decreased body weight gain during four weeks compared with the control group
Histological results revealed that the size of adipocytes in adipose tissue was significantly increased in the high fat diet (HFD) and Aβ-induced control group, compared with the normal diet (ND) and saline solution-induced normal group

Summary

Introduction

The imbalance of energy such as excessive intake of a high fat diet (HFD) is a major factor for obesity [1,2]. It leads to increased fat mass, changes in lipid profiles, and abnormalities in adipokine release in the body [3]. Obesity induced by HFD exacerbated cognitive and memory decline, whereas a low fat diet led to cognitive and memory improvement effects in mouse models in vivo [6]. Consumption of HFD increases amyloidosis-related factors such as beta-site amyloid beta precursor protein (APP) cleaving enzyme-1 (BACE-1), which elevates accumulation of Aβ plaques [8,9]. HFD induces oxidative stress, inflammation, brain insulin resistance, and synaptic dysfunction in cognitive function, and exacerbates cognitive dysfunction [9,10,11]

Results

Discussion

Conclusion