Mutant amyloid precursor protein differentially alters adipose biology under obesogenic and non-obesogenic conditions.
Mutations in amyloid precursor protein (APP) have been most intensely studied in brain tissue for their link to Alzheimer's disease (AD) pathology. However, APP is highly expressed in a variety of tissues including adipose tissue, where APP is also known to exhibit increased expression in response to obesity. In our current study, we analyzed the effects of mutant APP (E693Q, D694N, K670N/M671L) expression toward multiple aspects of adipose tissue homeostasis. These data reveal significant hypoleptinemia, decreased adiposity, and reduced adipocyte size in response to mutant APP, and this was fully reversed upon high fat diet administration. Additionally, mutant APP was observed to significantly exacerbate insulin resistance, triglyceride elevations, and macrophage infiltration of adipose tissue in response to a high fat diet. Taken together, these data have significant implications for linking mutant APP expression to adipose tissue dysfunction and global changes in endocrine and metabolic function under both obesogenic and non-obesogenic conditions.
Pennington Biomedical Research Center/LSU System, Baton Rouge, Louisiana, United States of America.
Linnea R
LR
Freeman
Le
L
Zhang
Kalavathi
K
Dasuri
Sun-Ok
SO
Fernandez-Kim
Annadora J
AJ
Bruce-Keller
Jeffrey N
JN
Keller
D017667:Adipocytes / Q000502:physiology; D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D059305:Diet, High-Fat; D004797:Enzyme-Linked Immunosorbent Assay; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D020738:Leptin / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D020125:Mutation, Missense / Q000235:genetics*; D009765:Obesity / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054392:Adipokines; D016564:Amyloid beta-Protein Precursor; D017931:DNA Primers; D020738:Leptin