Obesity Induced by Neonatal Monosodium Glutamate Treatment in Spontaneously Hypertensive Rats: An Animal Model of Multiple Risk Factors.

Abstract

The present study was designed to develop an animal model of multiple risk factors, including obesity, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR). Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension was attenuated in obese SHR as compared with control SHR. The degree of obesity was closely related to the metabolic abnormalities, but inversely correlated with the blood pressure level. Macrovascular changes were investigated in obese SHR at 14 months of age. Intimal thickening was accelerated in the carotid artery of obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total cholesterol were significantly increased in obese SHR. SHR associated with MSG-induced obesity showed major manifestations of metabolic syndrome X. This animal model may be useful to study the clustering of risk factors for the development of macrovascular diseases. (Hypertens Res 1998; 21: 1-6) Key Words: insulin resistance, diabetes mellitus, syndrome X, atherosclerosis, animal model Obesity, hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and hyperlipidemia frequently exist in the same individual, and clustering of these closely related risk factors markedly increases the incidence and prevalence of atherosclerotic diseases (1-7). Insulin resistance and consequent hyperinsulinemia or visceral fat accumulation may play a pathogenetic role in the clustering of risk factors, i. e. , metabolic syndrome X. However, the relationship among these risk factors, especially that between hypertension and other metabolic diseases, is controversial (5-8). Our understanding of metabolic syndrome X may be enhanced by the development of an animal model of this syndrome. We therefore designed the present study to induce experimental obesity in spontaneously hypertensive rats (SHR) by treatment with small or large doses of monosodium glutamate (MSG). MSG induces hypothalamic damage when given during neonatally, leading to stunted growth and obesity (9). We studied the effects of MSG-induced obesity on hypertension, glycemia, lipidemia, and the development of macrovascular changes in the obese SHR. Materials and MethodsSHR were from our inbred colony and were bred in specific-pathogen-free conditions at Kyushu University Animal Center, where both temperature and lighting (on from 8:00 am to 8:00 pm) were controlled. They had free access to tap water and a standard chow diet, which contained 51.6% carbohydrate, 24.8% protein, 7.0% minerals, 4.4% fat, and 3.5% cellulose (flea Japan Inc., Tokyo, Japan). Animals were cared for as directed by guidelines of Kyushu University. Female newborn SHR were treated intrap...

Type 2 Diabetes Mellitus in Obese Mouse Model Induced by Monosodium Glutamate

“…The obesity was not caused by polyphagia. It was said by Iwase et al [3] and Cameron et al [1] that obesity without polyphagia is due to the amount and frequency of MSG injection.…”

“…It was reported that the ventromedial nucleus of the hypothalamus was destroyed by injecting mice with goldthioglucose (GTG) [6,7] and that the injected mice showed polyphagia and obesity [8], thereafter becoming diabetic. On the other hand, there are few reports of injecting MSG into mice that already have a diabetic condition [1,9], and also few reports concerning diabetes in other experimental animals [3,5]. There is no report of ICR normal mice developing obesity without polyphagia and a diabetic condition by injecting MSG, and of the condition continuing over a long period.…”

Features of syndrome X develop in transgenic rats expressing a non-insulin responsive phosphoenolpyruvate carboxykinase gene

“…Hypertension, however, has been reported in IRS-1 deficient mice which are insulin resistant but not obese at 5±8 months of age [26]. It is interesting to note that when rats are made obese, either genetically [35] or by hypothalamic damage [36], and mated with spontaneously hypertensive rats, extreme hyperinsulinaemia and glucose intolerance can result but hypertension is not exacerbated [35] and can actually be attenuated [36]. These data illustrate that obese animals do not necessarily have hypertension and that hypertension is not directly related to the level of hyperinsulinaemia (at least in the short-term).…”

Efeito da sobreposição de um modelo de obesidade neuroendócrina experimental e hipertensão arterial sobre a pressão arterial, peso corporal e parâmetros metabólicos e renais de ratos

“…16 Ressalta-se que, em outros estudos da literatura, ratos Wistar são utilizados como controles dos ratos SHR. [17][18][19] Apesar do menor peso corporal verificado no período basal, os ratos WST + MSG e SHR + MSG tiveram, nas 12 semanas do estudo, um percentual maior de ganho de peso em relação aos animais controles. O menor peso inicial dos animais MSG deveu-se provavelmente à ação neurotóxica dessa droga, que determina menor secreção de hormônio do crescimento.…”