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.

• MeSH
• albuminurie etiologie   moč   MeSH
• analýza moči MeSH
• biologické markery krev   moč   MeSH
• časná diagnóza MeSH
• časové faktory MeSH
• cytokiny moč   MeSH
• epidermální růstový faktor moč   MeSH
• hypertriglyceridemie krev   komplikace   genetika   moč   MeSH
• lipidy krev   MeSH
• mediátory zánětu moč   MeSH
• metabolický syndrom krev   komplikace   genetika   moč   MeSH
• modely nemocí na zvířatech MeSH
• nemoci ledvin krev   etiologie   moč   MeSH
• potkani transgenní MeSH
• potkani Wistar MeSH
• prediktivní hodnota testů MeSH
• proteomika * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• cyklosporin toxicita   MeSH
• hypertriglyceridemie krev   moč   MeSH
• krysa rodu rattus MeSH
• kyseliny mastné omega-3 farmakologie   MeSH
• ledviny fyziologie   patologie   účinky léků   MeSH
• rybí oleje MeSH
• vitamin E farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH