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Obesity-induced chronic inflammation in C57Bl6J mice, a novel risk factor in the progression of renal AA amyloidosis?

Van Der Heijden, R. A., Sheedfar, F., Bijzet, J., Hazenberg, B. P., Koonen, D. P. & Heeringa, P., 1-May-2015, In : Obesity Facts. 8, p. 175 1 p.

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Background: Compelling evidence links obesity induced systemic inflammation to the development of chronic kidney disease (CKD). This systemic inflammation may result from exacerbated adipose inflammation. Besides the known detrimental effects of typical pro-inflammatory factors secreted by the adipose tissue (TNF-α, MCP-1 and IL-6) on the kidney, we hypothesize the enhanced obesity-induced secretion of serum amyloid A (SAA), an acute inflammatory protein, to play a key role in aggravating obesity-induced CKD. Methods: Groups of male C57Bl/6J mice (n = 99 in total) were fed a low (10% lard) or high (45% lard) fat diet for a maximum of 52 weeks. Mice were sacrificed after 24, 40 and 52 weeks. Whole blood samples, kidneys and adipose tissues were collected. The development of adipose and renal tissue inflammation was assessed on gene expression and protein level. Adipocytokine levels were measured in plasma samples. Results: A distinct inflammatory phenotype was observed in the adipose tissue of HFD mice prior to renal inflammation, which was associated with an early systemic elevation of TNF-α, leptin and SAA (1A-C). With aging, sclerotic lesions appeared in the kidney, the extent of which was severely aggravated by HFD feeding. Lesions exhibited typical amyloid characteristics (2A) and pathological severity positively correlated with bodyweight (2B). Interestingly, more SAA protein was detected in lesions of HFD mice. Conclusion: Our data suggest a causal link between obesity induced chronic inflammation and AA amyloidosis in C57Bl/6J mice. Though future studies are necessary to prove this causal link and to determine its relevance for the human situation, obesity may hence be considered a risk factor for the development and progression of renal AA amyloidosis in the course of CKD. (Figure Presented).
Original languageEnglish
Pages (from-to)175
Number of pages1
JournalObesity Facts
Volume8
Publication statusPublished - 1-May-2015

    Keywords

  • protein, lard, leptin, amyloid, serum amyloid A, adipocytokine, interleukin 6, obesity, amyloidosis, risk factor, mouse, European, chronic inflammation, inflammation, kidney, adipose tissue, human, blood, lipid diet, male, feeding, aging, chronic kidney disease, blood sampling, nephritis, secretion (process), phenotype, plasma, gene expression, kidney parenchyma

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