title: Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.
abstract: Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.
authors.affiliation: Department of Pathology &Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Roel A
authors.initials: RA
authors.lastname: van der Heijden
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Bijzet
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Wouter C
authors.initials: WC
authors.lastname: Meijers
authors.affiliation: Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR) and Department of Medicine, National University of Singapore, Singapore.
authors.forename: Gopala K
authors.initials: GK
authors.lastname: Yakala
authors.affiliation: Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Tri Q
authors.initials: TQ
authors.lastname: Nguyen
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: Experimental Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Bouke P C
authors.initials: BP
authors.lastname: Hazenberg
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
authors.affiliation: Department of Pathology &Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
mesh_terms: D054392:Adipokines / Q000097:blood; D000367:Age Factors; D000686:Amyloidosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006706:Homeostasis; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013997:Time Factors
chemical_list: D054392:Adipokines; D016207:Cytokines; D007328:Insulin; D008055:Lipids; D000685:Serum Amyloid A Protein