title: Obesity and Hepatic Steatosis Are Associated with Elevated Serum Amyloid Beta in Metabolically Stressed APPswe/PS1dE9 Mice.
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.
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan, ROC.
authors.forename: Feng-Shiun
authors.initials: FS
authors.lastname: Shie
authors.affiliation: Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC; Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Young-Ji
authors.initials: YJ
authors.lastname: Shiao
authors.affiliation: Institute of Neuroscience, Brain Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Yeh
authors.affiliation: Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Tsai-Teng
authors.initials: TT
authors.lastname: Tzeng
authors.affiliation: Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Hao-Chieh
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Fong-Lee
authors.initials: FL
authors.lastname: Huang
authors.affiliation: Institute of Neuroscience, Brain Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Huey-Jen
authors.initials: HJ
authors.lastname: Tsay
authors.affiliation: Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC; Ph.D. Program for Clinical Drug Discovery from Botanical Herbs, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: Hui-Kang
authors.initials: HK
authors.lastname: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000097:blood*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000097:blood*; D006801:Humans; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D008055:Lipids; D010446:Peptide Fragments; D053764:Presenilin-1; D014280:Triglycerides; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)