75
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references33

          • Record: found
          • Abstract: found
          • Article: not found

          Renal fibrosis: new insights into the pathogenesis and therapeutics.

          Youhua Liu (2006)
          Renal fibrosis is the inevitable consequence of an excessive accumulation of extracellular matrix that occurs in virtually every type of chronic kidney disease. The pathogenesis of renal fibrosis is a progressive process that ultimately leads to end-stage renal failure, a devastating disorder that requires dialysis or kidney transplantation. In a simplistic view, renal fibrosis represents a failed wound-healing process of the kidney tissue after chronic, sustained injury. Several cellular pathways, including mesangial and fibroblast activation as well as tubular epithelial-mesenchymal transition, have been identified as the major avenues for the generation of the matrix-producing cells in diseased conditions. Among the many fibrogenic factors that regulate renal fibrotic process, transforming growth factor-beta (TGF-beta) is one that plays a central role. Although defective matrix degradation may contribute to tissue scarring, the exact action and mechanisms of the matrix-degrading enzymes in the injured kidney have become increasingly complicated. Recent discoveries on endogenous antifibrotic factors have evolved novel strategies aimed at antagonizing the fibrogenic action of TGF-beta/Smad signaling. Many therapeutic interventions appear effective in animal models; however, translation of these promising results into humans in the clinical setting remains a daunting task. This mini-review attempts to highlight the recent progress in our understanding of the cellular and molecular pathways leading to renal fibrosis, and discusses the challenges and opportunities in developing therapeutic strategies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The association between age and nephrosclerosis on renal biopsy among healthy adults.

            Chronic kidney disease is common with older age and is characterized on renal biopsy by global glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. To see whether the prevalence of these histologic abnormalities in the kidney increases with age in healthy adults and whether histologic findings are explained by age-related differences in kidney function or chronic kidney disease risk factors. Cross-sectional study. Mayo Clinic, Rochester, Minnesota, from 1999 to 2009. 1203 adult living kidney donors. Core-needle biopsy of the renal cortex obtained during surgical implantation of the kidney, and medical record data of kidney function and risk factors obtained before donation. The prevalence of nephrosclerosis (> or =2 chronic histologic abnormalities) was 2.7% (95% CI, 1.1% to 6.7%) for patients aged 18 to 29 years, 16% (CI, 12% to 20%) for patients aged 30 to 39 years, 28% (CI, 24% to 32%) for patients aged 40 to 49 years, 44% (CI, 38% to 50%) for patients aged 50 to 59 years, 58% (CI, 47% to 67%) for patients aged 60 to 69 years, and 73% (CI, 43% to 90%) for patients aged 70 to 77 years. Adjustment for kidney function and risk factor covariates did not explain the age-related increase in the prevalence of nephrosclerosis. Kidney donors are selected for health and lack the spectrum or severity of renal pathologic findings in the general population. Kidney function and chronic kidney disease risk factors do not explain the strong association between age and nephrosclerosis in healthy adults. National Institutes of Health, U.S. Public Health Service.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice

              Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the development of metabolic inflammation remains speculative. Thus, we aimed to elucidate the sequence of inflammatory events in adipose and hepatic tissues to determine their contribution to the development of metabolic inflammation and insulin resistance (IR) in diet-induced obesity. To confirm our hypothesis that adipose tissue (AT) inflammation is initiated prior to hepatic inflammation, C57BL/6J male mice were fed a low-fat diet (LFD; 10% kcal fat) or high-fat diet (HFD; 45% kcal fat) for either 24, 40 or 52 weeks. Lipid accumulation and inflammation was measured in AT and liver. Glucose tolerance was assessed and plasma levels of glucose, insulin, leptin and adiponectin were measured at various time points throughout the study. With HFD, C57BL/6j mice developed a progressive obese phenotype, accompanied by IR at 24 and 40 weeks of HFD, but IR was attenuated after 52 weeks of HFD. AT inflammation was present after 24 weeks of HFD, as indicated by the increased presence of crown-like structures and up-regulation of pro-inflammatory genes Tnf, Il1β, Mcp1 and F4/80. As hepatic inflammation was not detected until 40 weeks of HFD, we show that AT inflammation is established prior to the development of hepatic inflammation. Thus, AT inflammation is likely to have a greater contribution to the development of IR compared to hepatic inflammation.
                Bookmark

                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                13 November 2015
                2015
                : 5
                : 16474
                Affiliations
                [1 ]Department of Pathology & Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands
                [2 ]Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands
                [3 ]Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands
                [4 ]Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR) and Department of Medicine, National University of Singapore , Singapore
                [5 ]Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO) , Leiden, The Netherlands
                [6 ]Department of Pathology, University Medical Center Utrecht , Utrecht, The Netherlands
                [7 ]Experimental Medicine, Maastricht University Medical Centre , Maastricht, The Netherlands
                [8 ]Department of Pediatrics, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands
                [9 ]Top Institute Food and Nutrition , Wageningen, The Netherlands
                Author notes
                Article
                srep16474
                10.1038/srep16474
                4643235
                26563579
                5c2798e2-7fda-4d32-9e75-328049b5e397
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 12 August 2015
                : 13 October 2015
                Categories
                Article

                Uncategorized
                Uncategorized

                Comments

                Comment on this article