Experimental rat models to study the metabolic syndrome

Abstract

Being the metabolic syndrome a multifactorial condition, it is difficult to find adequate experimental models to study this pathology. The obese Zucker rats, which are homozygous for the fa allele, present abnormalities similar to those seen in human metabolic syndrome and are a widely extended model of insulin resistance. The usefulness of these rats as a model of non-insulin-dependent diabetes mellitus is nevertheless questionable, and they neither can be considered a clear experimental model of hypertension. Some experimental models different from the obese Zucker rats have also been used to study the metabolic syndrome. Some derive from the spontaneously hypertensive rats (SHR). In this context, the most important are the obese SHR, usually named Koletsky rats. Hyperinsulinism, associated with either normal or slightly elevated levels of blood glucose, is present in these animals, but SHR/N-corpulent rats are a more appropriated model of non-insulin-dependent diabetes mellitus. The SHR/NDmc corpulent rats, a subline of SHR/N-corpulent rats, also exhibit metabolic and histopathologic characteristics associated with human metabolic disorders. A new animal model of the metabolic syndrome, stroke-prone -SHR (SHRSP) fatty rats, was obtained by introducing a segment of the mutant leptin receptor gene from the Zucker line heterozygous for the fa gene mutation into the genetic background of the SHRSP. Very recently, it has been developed as a non-obese rat model with hypertension, fatty liver and characteristics of the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein in the SHR rats. The Wistar Ottawa Karlsburg W rats are also a new strain that develops a nearly complete metabolic syndrome. Moreover, a new experimental model of low-capacity runner rats has also been developed with elevated blood pressure levels together with the other hallmarks of the metabolic syndrome.Zucker rats: Obesity: Metabolic syndrome: Insulin resistanceThe metabolic syndrome has been recognised in the medical literature for more than 80 years. The syndrome does not constitute one single illness. Instead, it can be defined as a group of health problems, caused by genetic and environmental factors, whose common fundamental pathogenic component is resistance to insulin. These problems may occur in one individual simultaneously or one by one, but their appearance together in one person is significant as these patients are more prone to CVD in general and to coronary disease in particular.In its Third Panel of Adult Treatment, part of the National Program for Cholesterol Education, the U.S. National Health Institute gave a definition of the metabolic syndrome based on risk factors, which is straightforward to apply in epidemiological studies and daily clinical practice (1) . This definition does not require direct demonstration of resistance to insulin, which in clinical practice may be difficult to establish. The metabolic syndrome is assumed to exist when three or more of the following risk factor...

Vitamin A status affects obesity development and hepatic expression of key genes for fuel metabolism in Zucker fatty rats

“…Zucker fatty (ZF) rats (Zucker and Zucker 1961) develop obesity due to a missense mutation in the extracellular domain of all leptin receptor isoforms (Iida et al 1996;Phillips et al 1996;Takaya et al 1996). They are rat models for obesity development, insulin resistance, and other aspects of metabolic diseases (Aleixandre de Artiñano and Miguel Castro 2009;Unger 1997). We hypothesize that VA status may affect the development of obesity in ZF rats.…”

Insight into the Potential Factors That Promote Tobacco Use in Vulnerable Populations

“…However, the latter survey also revealed that the decline in smoking rates over this period is lower in persons with diabetes, indicating a sustained use of tobacco in persons with diabetes. Pre-clinical studies have employed two common models of diabetes involving streptozotocin (STZ) administration or a chronic high-fat diet (HFD) regimen [61]. STZ is a drug that is taken up via glucose (type 2) transporters that are concentrated on the insulin-producing beta cells of the pancreas.…”

Overnutrition and the Cardiorenal Syndrome: Use of a Rodent Model to Examine Mechanisms

“…Mechanisms by which obesity and insulin resistance lead to kidney disease have been investigated in numerous models; however, the ZO rat is one of the best-characterized models for obesity-related kidney injury [47,48]. Observations from the ZO rat kidney suggest that activation of the renin-angiotensin system (RAS) in juxtaglomerular cells (fig.…”

“…4c) promotes a pro-inflammatory and pro-oxidative milieu (fig. 4b, d) and triggers obesity-induced mechanical forces which impair natriuresis and contribute to kidney injury [47,48,49]. These abnormalities, in turn, result in reductions in bioavailable NO, thus enhancing renal injury and progressive kidney disease [50,51].…”

“…These overweight-/obesity-related comorbidities appear to be driven, in part, by decreases in insulin metabolic signaling in cardiac and renal tissue (fig. 1) [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50]. In addition to insulin resistance, several other mechanisms, such as enhanced activation of the renin-angiotensin-aldosterone system (RAAS), inflammation and oxidative stress, may help explain the linkage between overnutrition and heart and kidney disease.…”