Obesity and hepatic steatosis are associated with elevated serum amyloid beta in metabolically stressed APPswe/PS1dE9 mice

Feng Shiun Shie, Young Ji Shiao, Chih Wen Yeh, Chien Hung Lin, Tsai Teng Tzeng, Hao Chieh Hsu, Fong Lee Huang, Huey Jen Tsay, Hui Kang Liu

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20 Scopus citations

Abstract

Diabesity-associated metabolic stresses modulate the development of Alzheimer's disease (AD). For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity. We characterized APPswe/PS1dE9 transgenic mice treated with a combination of high-fat diet with streptozotocin (HFSTZ) in the early stage of AD. HFSTZ-treated APPswe/PS1dE9 transgenic mice exhibited worse metabolic stresses related to diabesity, while serum β-amyloid levels were elevated and hepatic steatosis became apparent. Importantly, two-way analysis of variance shows a significant interaction between HFSTZ and genetic background of AD, indicating that APPswe/PS1dE9 transgenic mice are more vulnerable to HFSTZ treatment. In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson's correlation analysis. Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis. Alleviating metabolic stresses including dysglycemia, obesity, and hepatic steatosis could be critical to prevent peripheral β-amyloid accumulation at the early stage of AD.

Original languageEnglish
Article numbere0134531
JournalPLoS ONE
Volume10
Issue number8
DOIs
StatePublished - 5 Aug 2015

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