Elsevier

Nutrition Research

Volume 30, Issue 7, July 2010, Pages 483-491
Nutrition Research

A high-fat diet inhibits the progression of diabetes mellitus in type 2 diabetic rats

https://doi.org/10.1016/j.nutres.2010.06.013Get rights and content

Abstract

It is well known that rats and mice, when fed a high-fat diet, develop obesity associated with abnormal glycolipid metabolism. In this study, we investigated the effects of a high-fat diet on a diabetic rat model, Spontaneously Diabetic Torii (SDT), which develops diabetes due to decreased insulin production and secretion with age. We hypothesized that a high-fat diet would accelerate the induction of diabetes in this model. The SDT rats were divided into 2 groups, which were fed a high-fat diet or standard diet for 16 weeks. The group fed a high-fat diet developed obesity, hyperinsulinemia, and hyperlipidemia until 16 weeks of age. Before 16 weeks of age, hyperglycemia accompanied by hypoinsulinemia developed in the group on a standard diet, but serum glucose levels were comparable in both groups. After 16 weeks of age, the group on a standard diet showed an increase in serum glucose levels and a decrease in serum insulin levels. Unexpectedly, in the group on the high-fat diet, we observed a suppressed of the progression of hyperglycemia/hypoinsulinemia. Histopathological observation revealed more pancreatic beta cells in the group on the high-fat diet. This study suggests that feeding SDT rats a high-fat diet induces obesity, hyperinsulinemia, and hyperlipidemia, but not hyperglycemia, until 16 weeks of age. Thereafter, age-dependent progress of hyperglycemia and hypoinsulinemia was delayed by a high-fat diet. The hyperfunction of pancreatic beta cells induced by a high-fat diet before the onset of hyperglycemia appears to suppress development of hyperglycemia/hypoinsulinemia.

Introduction

Obesity is considered to be closely related to the development of diabetes, hyperlipidemia, and hypertension [1], [2], [3], and the metabolic syndrome concept has been established based on the pathophysiological relationship between obesity-related metabolic disorders and cardiovascular abnormalities [4], [5]. A key role of obesity in inducing metabolic syndrome is its role in increasing insulin resistance because insulin resistance is assumed to disturb both glucose and lipid metabolism and accelerate obesity through stimulating insulin secretion [6], [7], [8]. To investigate the effects of obesity on endocrine function and metabolism, genetic or dietary mouse and rat models of obesity are used [9], [10], [11]. Studies with these obese animals revealed that insulin resistance accelerated by obesity resulted in disturbed metabolism of glucose and lipids [10], [12].

Energy intake that exceeds energy expenditure induces an increase in body weight, which leads to obesity. According to several investigations, this disorder based on hyper-nutrition is not only increasing in Western countries but also in all regions of the world. Numerous studies on the relationship between diabetes and dietary composition have been conducted. It is necessary to follow both short and long experimental duration outcomes in these studies. In humans, the effect of a high-fat diet on diabetes has been reported to have conflicting results [13], [14]. Studies using a high-fat diet, which is used as a diabetogenic factor, have been reported for rats and mice. In standard strains of rats and mice, such as Sprague-Dawley (SD) rats and C57BL/6J mice, diet-induced obesity was accompanied by an increase in insulin and lipid levels but not always by an increase in blood glucose levels [15], [16], [17]. In the spontaneously diabetic rat model, Zucker diabetic fatty (ZDF), a high-fat diet accelerated the onset and severity of hyperglycemia [18]. Differences in the metabolic response to diet-induced obesity across animal strains are likely due to genetic backgrounds.

Spontaneously Diabetic Torii (SDT) rats develop diabetes independent of obesity [19], [20], [21]. They have normal body weights, blood glucose levels, insulin levels and lipid levels until about 16 weeks of age and, thereafter, develop hyperglycemia associated with hypoinsulinemia, which results from the degeneration of pancreatic beta cells [22], [23]. Spontaneously Diabetic Torii fatty rats have a spontaneous genetic mutation in the fa gene causing hyperphagia, leading to the development of hyperglycemia and hyperinsulinemia after about 5 weeks of age. Diabetic complications, such as cataracts or renal tubular lesions, have been observed from 8 weeks of age in these rats. Diabetes and its pathology are exhibited earlier in SDT fatty rats than other genetic strains [24]. Preventing hyperphagia in SDT fatty rats temporally has beneficial effects on body weight, hyperglycemia, and hypertriglyceridemia [25]. It was well known that the ingredients of one's diet are closely linked to the pathophysiology of type 2 diabetes. High-fat diets accelerated the onset and severity of type 2 diabetes in some spontaneously diabetic models [18]. In SDT fatty rats, diabetes is exhibited earlier than SDT rats because of hyperphagia (exceed energy intake).

In this study, the response of SDT rats to a high-fat diet was investigated to understand the predisposition to diabetes. We studied the effect of a high-fat diet on the biological parameters, glucose tolerance test results, fat tissue weights, and histopathological changes in some tissues. We hypothesized that a high-fat diet (high calorie diet) would accelerate the induction of diabetes in SDT rats compared with standard diets. This research is useful for understanding the effect of high-fat diets on the development of diabetes in both short- and long-term experiments.

Section snippets

Animals and diets

This experiment was conducted in compliance with the Guidelines for Animal Experimentation of our biological/pharmacological research laboratories. All the experiments obtained the approval of the Animal Experiment Committee of Japan Tobacco. Male SDT rats at 8 weeks of age from our colonies were used (Japan Tobacco Inc, Central Pharmaceutical Research Institute, Takatsuki, Japan). The rats were kept in metal cages, with 2 to 3 animals/cage in a climate-controlled room with a temperature of

Body weight and calorie intake

The caloric intake was comparable from 10 to 18 weeks of age between HF-SDT and SD-SDT rats; however, the caloric intake of SD-SDT rats was increased from 20 to 24 weeks of age (Fig. 1A). Body weight in SD-SDT rats continued to increase until 18 weeks of age (306.1 ± 21.9 g at 8 weeks and 534.8 ± 19.2 g at 18 weeks). After 16 weeks of age, body weight slightly decreased (516.2 ± 48.6 g at 24 weeks). In HF-SDT rats, body weight continued to increase until 18 weeks of age, and thereafter

Discussion

To induce experimental obesity in animals, high-fat diets have been used, and it is well recognized that dietary fat content is positively correlated with body weight gain [31]. Moreover, many rodent species develop obesity associated with various metabolic abnormalities, such as metabolic syndromes, which includes glucose intolerance, insulin resistance, and dyslipidemia [32], [33], [34]. Furthermore, the metabolic response to dietary fats can be variable across strains and sexes [16], [17].

In

Acknowledgment

This work was supported by Central Pharmaceutical Research Institute in Japan Tobacco Inc.

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