title: Amyloid precursor protein modulates macrophage phenotype and diet-dependent weight gain.
abstract: It is well known that mutations in the gene coding for amyloid precursor protein are responsible for autosomal dominant forms of Alzheimer's disease. Proteolytic processing of the protein leads to a number of metabolites including the amyloid beta peptide. Although brain amyloid precursor protein expression and amyloid beta production are associated with the pathophysiology of Alzheimer's disease, it is clear that amyloid precursor protein is expressed in numerous cell types and tissues. Here we demonstrate that amyloid precursor protein is involved in regulating the phenotype of both adipocytes and peripheral macrophages and is required for high fat diet-dependent weight gain in mice. These data suggest that functions of this protein include modulation of the peripheral immune system and lipid metabolism. This biology may have relevance not only to the pathophysiology of Alzheimer's disease but also diet-associated obesity.
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA.
authors.forename: Kendra L
authors.initials: KL
authors.lastname: Puig
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Brose
authors.affiliation: Department of Pathology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pathology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Sens
authors.affiliation: Grand Forks Human Nutrition Res. Center (GFHNRC), ARS-USDA, Grand Forks, ND 58201, USA.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Combs
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jensen
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA.
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Golovko
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA.
authors.forename: Colin K
authors.initials: CK
authors.lastname: Combs
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D004032:Diet; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D015430:Weight Gain / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D018836:Inflammation Mediators