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Vol. 90, No. 4, 2009
Issue release date: November 2009
Section title: Appetite, Energy Balance and Obesity
Neuroendocrinology 2009;90:383–390
(DOI:10.1159/000235555)

Plasma Amyloid-β Peptide Levels Correlate with Adipocyte Amyloid Precursor Protein Gene Expression in Obese Individuals

Lee Y.-H. · Martin J.M. · Maple R.L. · Tharp W.G. · Pratley R.E.
Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Burlington, Vt., USA

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Article / Publication Details

First-Page Preview
Abstract of Appetite, Energy Balance and Obesity

Received: 4/29/2008
Accepted: 4/17/2009
Published online: 8/12/2009

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 1

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN

Abstract

Background/Aims: Several studies have demonstrated that midlife obesity increases the risk for dementia and Alzheimer’s disease. Moreover, plasma 42-amino-acid amyloid-β (Aβ42) levels appear to correlate with BMI. We recently demonstrated that adipocyte amyloid precursor protein (APP) expression is upregulated in obesity and correlates with insulin resistance and adipose tissue inflammation. In this study, we aimed to investigate the relation between adipocyte APP expression and plasma Aβ peptide levels. Methods: We conducted a pilot study in which we measured adipocyte APP gene expression and the circulating plasma levels of Aβ40 in 10 obese individuals before and after a 6-month behaviorally based weight loss intervention. Subjects had an oral glucose tolerance test with measurement of insulin levels, Aβ40 levels measured by ELISA and transcript levels of APP in subcutaneous abdominal adipocytes measured by quantitative real-time PCR. Results: At baseline, adipocyte APP expression correlated significantly with plasma Aβ40 levels and with 2-hour insulin concentrations. Following the 6-month weight loss intervention, body weight and BMI decreased significantly. Fasting plasma concentrations of glucose and insulin were improved. Adipocyte APP expression was significantly decreased (p < 0.001) after weight loss. Changes in adipocyte APP expression correlated with changes in plasma Aβ40 levels (R = 0.74, p = 0.01) and changes in 2-hour insulin (R = 0.75, p = 0.01). Conclusion: The results of this pilot study suggest that increased circulating plasma levels of Aβ peptides in obesity may be due to increased adipocyte APP gene expression. While these results suggest a possible mechanism linking midlife obesity with the later development of Alzheimer’s disease, further research is necessary to elucidate the regulation and functional significance of APP in adipocytes.


Article / Publication Details

First-Page Preview
Abstract of Appetite, Energy Balance and Obesity

Received: 4/29/2008
Accepted: 4/17/2009
Published online: 8/12/2009

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 1

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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