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


      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.


      To read this article in full you will need to make a payment


        • Howard B.V.
        Lipoprotein metabolism in diabetes mellitus.
        J. Lipid Res. 1987; 28: 613-628
        • Garcia M.J.
        • McNamara P.M.
        • Gordon T.
        • Kannel W.B.
        Morbidity and mortality in diabetics in the Framingham population. Sixteen year follow-up study.
        Diabetes. 1974; 23: 105-111
        • Steiner G.
        Diabetes and atherosclerosis: an overview.
        Diabetes. 1981; 30: 1-7
        • Havel P.J.
        • Uriu-Hare J.Y.
        • Liu T.
        • Stanhope K.L.
        • Stern J.S.
        • Keen C.L.
        • et al.
        Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin.
        Am. J. Physiol. 1998; 274: R1482-R1491
        • Young N.L.
        • Saudek C.D.
        • Walters L.
        • Lapeyrolerie J.
        • Chang V.
        Preventing hyperphagia normalizes 3-hydroxy-3-methylglutaryl-CoA reductase activity in small intestine and liver of diabetic rats.
        J. Lipid Res. 1982; 23: 831-838
        • Redgrave T.G.
        • Snibson D.A.
        Clearance of chylomicron triacylglycerol and cholesteryl ester from the plasma of streptozotocin-induced diabetic and hypercholesterolemic hypothyroid rats.
        Metabolism. 1977; 26: 493-503
        • Steiner G.
        • Poapst M.
        • Davidson J.K.
        Production of chylomicron-like lipoproteins from endogenous lipid by the intestine and liver of diabetic dogs.
        Diabetes. 1975; 24: 263-271
        • Risser T.R.
        • Reaven G.M.
        • Reaven E.P.
        Intestinal very low density lipoprotein secretion in insulin-deficient rats.
        Diabetes. 1978; 27: 902-908
        • Popper D.A.
        • Shiau Y.F.
        • Reed M.
        Role of small intestine in pathogenesis of hyperlipidemia in diabetic rats.
        Am. J. Physiol. 1985; 249: G161-G167
        • Shinohara M.
        • Masuyama T.
        • Shoda T.
        • Takahashi T.
        • Katsuda Y.
        • Komeda K.
        • et al.
        A new Spontaneously Diabetic Non-Obese Torii rat strain with severe ocular complications.
        Int. J. Exp. Diabetes Res. 2000; 1: 89-100
        • Sasase T.
        • Ohta T.
        • Ogawa N.
        • Miyajima K.
        • Ito M.
        • Yamamoto H.
        • et al.
        Preventive effects of glycaemic control on ocular complications of Spontaneously Diabetic Torii rat.
        Diabetes Obes. Metab. 2006; 8: 501-507
        • Usui S.
        • Hara Y.
        • Hosaki S.
        • Okazaki M.
        A new on-line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC.
        J. Lipid Res. 2002; 43: 805-814
        • Okazaki M.
        • Usui S.
        • Ishigami M.
        • Sakai N.
        • Nakamura T.
        • Matsuzawa Y.
        • et al.
        Identification of unique lipoprotein subclasses for visceral obesity by component analysis of cholesterol profile in high-performance liquid chromatography.
        Arterioscler. Thromb. Vasc. Biol. 2005; 25: 578-584
        • Gleeson A.
        • Anderton K.
        • Owens D.
        • Bennett A.
        • Collins P.
        • Johnson A.
        • et al.
        The role of microsomal triglyceride transfer protein and dietary cholesterol in chylomicron production in diabetes.
        Diabetologia. 1999; 42: 944-948
        • Masuyama T.
        • Komeda K.
        • Hara A.
        • Noda M.
        • Shinohara M.
        • Oikawa T.
        • et al.
        Chronological characterization of diabetes development in male Spontaneously Diabetic Torii rats.
        Biochem. Biophys. Res. Commun. 2004; 314: 870-877
        • Yamada K.
        • Hosokawa M.
        • Fujimoto S.
        • Nagashima K.
        • Fukuda K.
        • Fujiwara H.
        • et al.
        The Spontaneously Diabetic Torii rat with gastroenteropathy.
        Diabetes Res. Clin. Pract. 2007; 75: 127-134
        • Sasase T.
        • Ohta T.
        • Ogawa N.
        • Miyajima K.
        • Koizumi H.
        • Matsushita M.
        • et al.
        Diabetic complications of Spontaneously Diabetic Torii rat.
        Diabetes. 2005; 54: A221
        • Brown D.F.
        Triglyceride metabolism in the alloxan-diabetic rat.
        Diabetes. 1967; 16: 90-95
        • Reaven E.P.
        • Reaven G.M.
        Mechanisms for development of diabetic hypertrigryceridemia in streptozotocin-treated rats. Effect of diet and duration of insulin deficiency.
        J. Clin. Invest. 1974; 54: 1167-1178
        • Bar-On H.
        • Roheim P.S.
        • Eder H.A.
        Serum lipoproteins and apolipoproteins in rats with streptozotocin-induced diabetes.
        J. Clin. Invest. 1976; 57: 714-721
        • Staprans I.
        • Pan X.M.
        • Rapp J.H.
        • Feingold K.R.
        Chylomicron and chylomicron remnant metabolism in STZ-induced diabetic rats.
        Diabetes. 1992; 41: 325-333
        • Friedman M.
        • Byers S.O.
        Mechanism of excessive postprandial lipemia in the diabetic rat.
        Proc. Soc. Exp. Biol. Med. 1969; 130: 132-136
        • Redgrave T.G.
        • Callow M.J.
        The effect of insulin deficiency on the metabolism of lipid emulsion models of triacylglycerol-rich lipoproteins in rats.
        Metabolism. 1990; 39: 1-10
        • Martins I.J.
        • Sainsbury A.J.
        • Mamo J.C.
        • Redgrave T.G.
        Lipid and apolipoprotein B48 transport in mesenterie lymph and the effect of hyperphagia on the clearance of chylomicron-like emulsions in insulin-deficient rats.
        Diabetologia. 1994; 37: 238-246
        • Mamo J.C.
        • Hirano T.
        • Sainsbury A.
        • Fitzgerald A.K.
        • Redgrave T.G.
        Hypertriglyceridemia is exacerbated by slow lipolysis of triacylglycerol-rich lipoproteins in fed but not fasted streptozotocin diabetic rats.
        Biochim. Biophys. Acta. 1992; 1128: 132-138
        • O’Looney P.
        • Irwin D.
        • Briscoe P.
        • Vahouny G.V.
        Lipoprotein composition as a component in the lipoprotein clearance defect in experimental diabetes.
        J. Biol. Chem. 1985; 260: 428-432
        • Mostafa N.
        • Bhat B.G.
        • Coleman R.A.
        Increased hepatic monoacylglycerol acyltransferase activity in streptozotocin-induced diabetes: characterization and comparison with activities from adult and neonatal rat liver.
        Biochim. Biophys. Acta. 1993; 1169: 189-195
        • Lin M.C.
        • Gordon D.
        • Wetterau J.R.
        Microsomal triglyceride transfer protein (MTP) regulation in HepG2 cells: insulin negatively regulates MTP gene expression.
        J. Lipid. Res. 1995; 36: 1073-1081
        • Chen H.C.
        • Smith S.J.
        • Ladha Z.
        • Jensen D.R.
        • Ferreira L.D.
        • Pulawa L.K.
        • et al.
        Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1.
        J. Clin. Invest. 2002; 109: 1049-1055
        • Meegalla R.L.
        • Billheimer J.T.
        • Cheng D.
        Concerted elevation of acyl-coenzyme A: diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin.
        Biochem. Biophys. Res. Commun. 2002; 298: 317-323
        • Au W.S.
        • Kung H.F.
        • Lin M.C.
        Regulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: roles of MAPKerk and MAPKp38.
        Diabetes. 2003; 52: 1073-1080