Increased fat absorption and impaired fat clearance cause postprandial hypertriglyceridemia in Spontaneously Diabetic Torii rat

https://doi.org/10.1016/j.diabres.2007.02.020Get rights and content

Abstract

In diabetes, postprandial hyperlipidemia is recognized as a risk factor for premature atherosclerosis and following cardiovascular disease. In the present study, features of fat absorption and clearance were examined to clarify the lipid metabolism of Spontaneously Diabetic Torii (SDT) rats. Olive oil was orally administered to evaluate increase of blood triglyceride (TG) level. Mesenteric lymph chylomicron TG was also measured. mRNAs of enzymes and transfer protein related to TG metabolism and histopathological changes were evaluated. In an oil loading test, elevation of TG in plasma and lymph chylomicron was increased in SDT rats. Interestingly, SDT rats showed elevation of plasma TG after oil loading and relatively low epididymal fat lipoprotein lipase (LPL) mRNA expression even at the pre-diabetic state without increase of TG absorption from intestine. In the diabetic state, intestines of SDT rats were hypertrophic and expressed mRNAs of enzymes and transfer protein related to TG absorption highly. From these results, it seems that intestinal abnormalities related to hypoinsulinemia/hyperglycemia cause postprandial hypertriglyceridemia in SDT rats. In addition, our findings suggest that SDT rats have impaired lipid catabolism antecedent to hypoinsulinemia/hyperglycemia. These characteristics of SDT rats can be useful in studies of diabetic hypertriglyceridemia and TG metabolism.

Introduction

Hypertriglyceridemia (HTG) is one of the major abnormalities found in diabetes with insulin deficiency [1], and is thought closely related to coronary heart disease and atherosclerosis, important complications of diabetes [2], [3]. Decreased signals of insulin and leptin cause diabetic hyperphagia [4], and are explanation for HTG. In diabetic state, hyperphagia leads to intestinal hypertrophy [5], which contributes to increased cholesterol synthesis and lipid absorption. Defect in plasma chylomicron clearance is another cause of diabetic HTG [6]. Triglyceride (TG) absorbed from intestine are transported into circulation by chylomicrons, and are cleared from circulation by lipoprotein lipase (LPL). Therefore, the impaired chylomicron catabolism is a concern in diabetic HTG. In addition, overproduction of the TG-rich lipoprotein may contribute to diabetic HTG. Earlier studies indicate that increased TG absorption from the small intestine contributes to HTG in diabetes [7], [8], [9].

Spontaneously Diabetic Torii (SDT) rat is a non-obese diabetes model which shows marked hyperglycemia and hypoinsulinemia [10]. The most distinctive features of SDT rats are severe ocular complications such as cataracts, tractional retinal detachment with fibrous proliferation, and massive hemorrhaging in the anterior chamber [10]. Previous study demonstrated that these ocular complications are derived from hyperglycemia and thus SDT rats are useful as a model of diabetic retinopathy [11]. In addition to these characteristics, SDT rats show HTG accompanied by hypoinsulinemia/hyperglycemia; however, details of HTG and lipid metabolism in SDT rats have not been clarified. In the present study, we examined the contribution of fat absorption and clearance to HTG in SDT rats.

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Animals

Male SDT rats (CLEA Japan, Tokyo, Japan) were used in the study. SDT rats did not show hyperglycemia/hypoinsulinemia at 8 weeks. At 16 weeks, approximately half of the SDT rats showed hyperglycemia. Age-matched Sprague–Dawley (SD) rats were used as control animals. All animal protocols used for the study were in strict compliance with our own “Laboratory Guidelines for Animal Experimentation”. Animals were housed in a climate-controlled room (temperature 23 ± 3 °C, humidity 55 ± 15%, 12 h lighting

Biochemical parameters

SDT rats showed lower body weight, marked hyperglycemia, hypoinsulinemia, and HTG at 30 weeks of age (Table 1). The major increase of TG in the circulation of SDT rats occurs in the TG-rich lipoprotein fraction: chylomicron (Fig. 1). TC level was not significantly different; however, in SDT rats, HDL-C level was significantly lower and non-HDL-C level was significantly higher than those of SD rats. Food consumption of SDT rats was gradually increased after onset of hyperglycemia and reached

Discussion

SDT rat is a type 2 diabetes model without obesity, found by Shinohara et al. [10]. SDT rats show severe hypoinsulinemia/hyperglycemia caused by pathological damage to the pancreatic islets, especially β-cells [15]. In addition to severe diabetic vascular complications, SDT rat shows HTG as same as other diabetic animal models. In the present study, we examined the lipid metabolism, especially the characteristics concerned with fat absorption and clearance of SDT rats.

In diabetes with poor

Acknowledgements

We sincerely appreciate the technical advice and expertise provided by Dr. Hiroshi Okamoto and Dr. Makoto Kakutani. We are grateful to Makoto Ito, Sumiaki Fukuda, Kaoru Sakata, Tomohiro Oda and Hironobu Tadaki for their technical assistance. We also wish to thank Akimitsu Takatsuka, Reiko Takata and Akiyuki Takahashi (JT Creative Service) for long-term animal care.

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