scholarly journals The Effect of Lipotoxicity on Renal Dysfunction in a Nonobese Rat Model of Metabolic Syndrome: A Urinary Proteomic Approach

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Irena Markova ◽  
Denisa Miklankova ◽  
Martina Hüttl ◽  
Petr Kacer ◽  
Jelena Skibova ◽  
...  

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.

2001 ◽  
Vol 16 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Koichi Nakanishi ◽  
Vincent H. Gattone II ◽  
William E. Sweeney ◽  
Ellis D. Avner

2020 ◽  
pp. 1085-1094
Author(s):  
I Lazúrová ◽  
I Jochmanová ◽  
Š Sotak ◽  
I Špaková ◽  
M Mareková

Adrenal incidentalomas (AI) are very common and mostly they are non-functioning adenomas (NFA). NFAs are often associated with insulin resistance and metabolic syndrome. Several biomarkers, including certain growth factors, may participate in the pathogenesis of metabolic changes in patients with adrenal adenomas. Patients with NFA and age-matched control subjects were enrolled in the study. Data on age, gender, presence of metabolic syndrome or its components were obtained for each subject. Blood samples were obtained and glycemia, insulinemia, lipid profile, and selected growth factor levels were measured. Forty-three patients with NFA and 40 controls were included in the study. Differences were not found in the metabolic syndrome and its components prevalence or in the biochemical profile between patients and the control group. Significant differences were noticed in the levels of IGF1, IGF2, and IGFBP3 (p=0.016, p=0.005, p=0.004, respectively), but there were no differences in VEGF or EGF concentrations. In NFA patients, an association between glycemia and EGF levels was present (p=0.026). No significant correlations between tumor size and insulin or growth factor concentrations were present in AI patients. Significantly higher serum IGF1, IGF2, and IGFBP3 concentrations in NFA patients may support the role of the IGF axis in the pathogenesis of adrenocortical lesions. No correlation between IGFs or IGFBP3 and parameters of glucose or lipid metabolism was found. Present results may support the role of the growth hormone axis rather than hyperinsulinemia and insulin resistance in the pathogenesis of adrenocortical adenomas.


2001 ◽  
Vol 120 (5) ◽  
pp. A11-A12 ◽  
Author(s):  
A SINHA ◽  
J NIGHTINGALE ◽  
K WEST ◽  
R PLAYFORD

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