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The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach
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SYSNO ASEP 0522791 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach Author(s) Marková, I. (CZ)
Mildankova, D. (CZ)
Hüttl, M. (CZ)
Kačer, P. (CZ)
Skibová, J. (CZ)
Kučera, Jan (UMG-J)
Sedláček, Radislav (UMG-J) RID
Kačerová, T. (GB)
Kazdová, L. (CZ)
Malínská, H. (CZ)Number of authors 10 Article number 8712979 Source Title Journal of Diabetes Research. - : Hindawi - ISSN 2314-6745
Roč. 2019, December (2019)Number of pages 10 s. Publication form Online - E Language eng - English Country GB - United Kingdom Keywords epidermal-growth-factor ; perirenal fat thickness ; chronic kidney-disease ; insulin-resistance ; independent predictor ; diabetic-nephropathy ; inflammation ; microalbuminuria ; association ; biomarkers Subject RIV EB - Genetics ; Molecular Biology OECD category Endocrinology and metabolism (including diabetes, hormones) R&D Projects LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000503425300002 DOI 10.1155/2019/8712979 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2020 Electronic address https://www.hindawi.com/journals/jdr/2019/8712979/
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