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Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

van der Heijden, R. A., Bijzet, J., Meijers, W. C., Yakala, G. K., Kleemann, R., Nguyen, T. Q., de Boer, R. A., Schalkwijk, C. G., Hazenberg, B. P. C., Tietge, U. J. F. & Heeringa, P., 13-Nov-2015, In : Scientific Reports. 5, 15 p., 16474.

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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.

Original languageEnglish
Article number16474
Number of pages15
JournalScientific Reports
Volume5
Publication statusPublished - 13-Nov-2015

    Keywords

  • CHRONIC KIDNEY-DISEASE, ADIPOSE-TISSUE, CARDIOVASCULAR-DISEASE, DEVELOPING-COUNTRIES, AA AMYLOIDOSIS, NUTRITION, CONSEQUENCES, NOMENCLATURE, CHOLESTEROL, PREVALENCE

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