The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach
Introduction. The development of metabolic syndrome-associated renal dysfunction is exacerbated by a number of factors including dyslipidemia, ectopic deposition of lipids and their toxic metabolites, impairment of lipid metabolism, and insulin resistance. Renal dysfunction is also affected by the p...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2019/8712979 |
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| author | Irena Markova Denisa Miklankova Martina Hüttl Petr Kacer Jelena Skibova Jan Kucera Radislav Sedlacek Tereza Kacerova Ludmila Kazdova Hana Malinska |
| author_facet | Irena Markova Denisa Miklankova Martina Hüttl Petr Kacer Jelena Skibova Jan Kucera Radislav Sedlacek Tereza Kacerova Ludmila Kazdova Hana Malinska |
| author_sort | Irena Markova |
| collection | DOAJ |
| description | Introduction. The development of metabolic syndrome-associated renal dysfunction is exacerbated by a number of factors including dyslipidemia, ectopic deposition of lipids and their toxic metabolites, impairment of lipid metabolism, and insulin resistance. Renal dysfunction is also affected by the production of proinflammatory and profibrotic factors secreted from adipose tissue, which can in turn directly impair kidney cells and potentiate insulin resistance. In this study, we investigated the manifestation of renal lipid accumulation and its effect on renal dysfunction in a model of metabolic syndrome—the hereditary hypertriglyceridemic rat (HHTg)—by assessing microalbuminuria and targeted urinary proteomics. Male Wistar control rats and HHTg rats were fed a standard diet and observed over the course of ageing at 3, 12, and 20 months of age. Results. Chronically elevated levels of triglycerides in HHTg rats were associated with increased levels of NEFA during OGTT and over a period of 24 hours (+80%, P<0.01). HHTg animals exhibited qualitative changes in NEFA fatty acid composition, represented by an increased proportion of saturated fatty acids (P<0.05) and a decreased proportion of n-3 PUFA (P<0.01). Ectopic lipid deposition in the kidneys of HHTg rats—triglycerides (+30%) and cholesterol (+10%)—was associated with markedly elevated microalbuminuria as ageing increased, despite the absence of microalbuminuria at the young age of 3 months in these animals. According to targeted proteomic analysis, 3-month-old HHTg rats (in comparison to age-matched controls) exhibited increased urinary secretion of proinflammatory parameters (MCP-1, IL-6, IL-8, P<0.01) and decreased urinary secretion of epidermal growth factor (EGF, P<0.01) before manifestation of microalbuminuria. Elevation in the urinary secretion of inflammatory cytokines can be affected by increased relative expression of MCP-1 in the renal cortex (P<0.05). Conclusions. Our results confirm dyslipidemia and ectopic lipid accumulation to be key contributors in the development of metabolic syndrome-associated renal dysfunction. Assessing urinary secretion of proinflammatory cytokines and epidermal growth factor can help in detecting early development of metabolic syndrome-associated renal dysfunction. |
| format | Article |
| id | doaj-art-ab06606989474a81b1ad75c48b777697 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Journal of Diabetes Research |
| spelling | doaj-art-ab06606989474a81b1ad75c48b7776972025-02-03T01:11:02ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/87129798712979The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic ApproachIrena Markova0Denisa Miklankova1Martina Hüttl2Petr Kacer3Jelena Skibova4Jan Kucera5Radislav Sedlacek6Tereza Kacerova7Ludmila Kazdova8Hana Malinska9Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCzech University of Life Sciences, 16500 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, 25250 Vestec, Czech RepublicCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, 25250 Vestec, Czech RepublicDepartment of Chemistry, University College London, London WC1H 0AJ, UKCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicIntroduction. The development of metabolic syndrome-associated renal dysfunction is exacerbated by a number of factors including dyslipidemia, ectopic deposition of lipids and their toxic metabolites, impairment of lipid metabolism, and insulin resistance. Renal dysfunction is also affected by the production of proinflammatory and profibrotic factors secreted from adipose tissue, which can in turn directly impair kidney cells and potentiate insulin resistance. In this study, we investigated the manifestation of renal lipid accumulation and its effect on renal dysfunction in a model of metabolic syndrome—the hereditary hypertriglyceridemic rat (HHTg)—by assessing microalbuminuria and targeted urinary proteomics. Male Wistar control rats and HHTg rats were fed a standard diet and observed over the course of ageing at 3, 12, and 20 months of age. Results. Chronically elevated levels of triglycerides in HHTg rats were associated with increased levels of NEFA during OGTT and over a period of 24 hours (+80%, P<0.01). HHTg animals exhibited qualitative changes in NEFA fatty acid composition, represented by an increased proportion of saturated fatty acids (P<0.05) and a decreased proportion of n-3 PUFA (P<0.01). Ectopic lipid deposition in the kidneys of HHTg rats—triglycerides (+30%) and cholesterol (+10%)—was associated with markedly elevated microalbuminuria as ageing increased, despite the absence of microalbuminuria at the young age of 3 months in these animals. According to targeted proteomic analysis, 3-month-old HHTg rats (in comparison to age-matched controls) exhibited increased urinary secretion of proinflammatory parameters (MCP-1, IL-6, IL-8, P<0.01) and decreased urinary secretion of epidermal growth factor (EGF, P<0.01) before manifestation of microalbuminuria. Elevation in the urinary secretion of inflammatory cytokines can be affected by increased relative expression of MCP-1 in the renal cortex (P<0.05). Conclusions. Our results confirm dyslipidemia and ectopic lipid accumulation to be key contributors in the development of metabolic syndrome-associated renal dysfunction. Assessing urinary secretion of proinflammatory cytokines and epidermal growth factor can help in detecting early development of metabolic syndrome-associated renal dysfunction.http://dx.doi.org/10.1155/2019/8712979 |
| spellingShingle | Irena Markova Denisa Miklankova Martina Hüttl Petr Kacer Jelena Skibova Jan Kucera Radislav Sedlacek Tereza Kacerova Ludmila Kazdova Hana Malinska The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach Journal of Diabetes Research |
| title | The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach |
| title_full | The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach |
| title_fullStr | The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach |
| title_full_unstemmed | The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach |
| title_short | The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach |
| title_sort | effect of lipotoxicity on renal dysfunction in a nonobese rat model of metabolic syndrome a urinary proteomic approach |
| url | http://dx.doi.org/10.1155/2019/8712979 |
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