Abstract
BackgroundThe obese Zücker diabetic fatty male rat (ZDF:Gmi™-fa) is an animal model of type II diabetes associated with obesity and related metabolic disturbances like dyslipidaemia and diabetic nephropathy. In addition, diabetic dyslipidaemia has been linked to vascular and glomerular damage too. Dietary fat restriction is a current strategy to tackle obesity and, telmisartan, as a renoprotective agent, may mediate cholesterol efflux by activating PPARγ. To test the hypothesis that both therapeutical alternatives may influence dyslipidaemia and nephropathy in the ZDF rat, we studied their effect on development of diabetes.MethodsMale Zücker Diabetic Fatty (ZDF) rats received a low-calorie diet, vehicle or telmisartan for 9 weeks. Blood samples were obtained for analyses of lipids and lipoproteins, LDL-oxidisability, HDL structural and functional properties. Urinalysis was carried out to estimate albumin loss. At the end of the experimental period, rats were sacrificed, liver extracted and APOA1 mRNA quantified.ResultsResults indicated that low-calorie diet and telmisartan can slower the onset of overt hyperglycaemia and renal damage assessed as albuminuria. Both interventions decreased the oxidative susceptibility of LDL and hepatic APOA1 mRNA expression but only dietary restriction lowered hyperlipidaemia.ConclusionEither a dietary or pharmacologic interventions with telmisartan have important beneficial effects in terms of LDL oxidative susceptibility and progression of albuminuria in obesity related type II diabetes.
Highlights
The obese Zücker diabetic fatty male rat (ZDF:GmiTM-fa) is an animal model of type II diabetes associated with obesity and related metabolic disturbances like dyslipidaemia and diabetic nephropathy
Apolipoprotein A1 (APOA1) plays a key role for cholesterol efflux, but there are other components of the High density lipoprotein (HDL) particle such as apolipoproteins, antioxidant enzymes or lipids besides cholesterol that confer HDL its beneficial properties [8]
In patients with certain diseases, the different proteins and lipids commonly found in HDL particles may undergo modifications such as amino acid oxidation, protein loss, proteolytic degradation, protein glycation, and many other harmful modifications that interfere with HDL function [9,10]
Summary
The obese Zücker diabetic fatty male rat (ZDF:GmiTM-fa) is an animal model of type II diabetes associated with obesity and related metabolic disturbances like dyslipidaemia and diabetic nephropathy. Incidence and prevalence of obesity and diabetes have increased considerably in recent years [1,2] They both represent a major public health concern in terms of morbidity and mortality, due to their association with cardiovascular disorders, resulting from metabolic disturbances (atherogenic dyslipidaemia and hyperglycaemia), inflammatory status and endothelial dysfunction that led to atherosclerosis [3,4]. Zücker obese and diabetic rat (ZDF/Gmi-fa) is an animal model frequently used to study obesity and related metabolic disturbances like dyslipidaemia and non-insulin dependent diabetes [5]. HDL particles inhibit many inflammatory activities, inhibit oxidation of lipoproteins and cell membranes, and help to maintain endothelial function and integrity too They exert anticoagulant effects by inhibiting coagulation proteins and platelet aggregation. In patients with certain diseases (diabetes, cardiovascular diseases, etc.), the different proteins and lipids commonly found in HDL particles may undergo modifications such as amino acid oxidation, protein loss, proteolytic degradation, protein glycation, and many other harmful modifications that interfere with HDL function [9,10]
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