有哪些信誉好的足球投注网站amyloid precursor protein and proinflammatory changes are regulated in brain and adipose tissue in a murine model of high fat diet-induced obesity淀粉样前体蛋白和促炎的变化调节大脑和脂肪组织在一个高脂肪食源性肥胖小鼠模型.pdfVIP
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amyloid precursor protein and proinflammatory changes are regulated in brain and adipose tissue in a murine model of high fat diet-induced obesity淀粉样前体蛋白和促炎的变化调节大脑和脂肪组织在一个高脂肪食源性肥胖小鼠模型
Amyloid Precursor Protein and Proinflammatory
Changes Are Regulated in Brain and Adipose Tissue in a
Murine Model of High Fat Diet-Induced Obesity
Kendra L. Puig, Angela M. Floden, Ramchandra Adhikari, Mikhail Y. Golovko, Colin K. Combs*
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, United States
of America
Abstract
Background: Middle age obesity is recognized as a risk factor for Alzheimer’s disease (AD) although a mechanistic linkage
remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a
possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in
the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent
evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in
both disease conditions.
Methodology/Principal Findings: To determine whether diet-induced obesity produced proinflammatory changes and
altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet
for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation
were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent
changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes.
Conclusions/Significance: Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-a and
microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neur
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