Intestinal rather than hepatic microsomal triglyceride transfer protein as a cause of postprandial dyslipidemia in diabetes.
Postprandial dyslipidemia may be a major cause of atherosclerosis in diabetes. Microsomal triglyceride transfer protein (MTP) is essential for the synthesis of the chylomicron particle in the intestine and very low-density lipoprotein (VLDL) in the liver. The purpose of the present study was to examine the effect of diabetes on MTP mRNA expression in a rabbit model of diabetes, which develops atherosclerosis. Male New Zealand white rabbits were fed a 0.5% cholesterol diet. Diabetes was induced with alloxan monohydrate. The lymphatic duct was cannulated and lymph collected for isolation of chylomicrons by ultracentrifugation. Apolipoprotein B48 (apo B48) and apo B100 were separated by polyacrylamide gradient gel electrophoresis and quantified by densitometry. MTP mRNA was determined in liver and intestine by RNase protection analysis, and MTP activity was measured. Diabetic animals had significantly increased plasma triglyceride and decreased high-density lipoprotein (HDL) cholesterol (P <.05). They also secreted more lymph chylomicron apo B48 and apo B100 (P <.05) and more lymph chylomicron total and esterified cholesterol/h (P <.05). Lymph chylomicron particles in the diabetic animals contained significantly less lipid/apo B (P <.05). Intestinal MTP activity and mRNA were significantly higher in diabetic compared with control rabbits (0.07 +/- 0.01 v 0.04 +/- 0.015 fluorescent units/microg microsomal protein and 66 +/- 21 v 37 +/- 11 amol MTP mRNA/microg total RNA (P <.005). There was no difference in MTP activity or mRNA expression in the liver. This study suggests that MTP may play an important role in the postprandial dyslipidemia of diabetes.
Phillips
Catherine
C
Department of Clinical Medicine, Trinity College, Dublin, Ireland.
Bennett
Andrew
A
Anderton
Kay
K
Owens
Daphne
D
Collins
Patrick
P
White
David
D
Tomkin
Gerald H
GH
D000496:Alloxan; D000818:Animals; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000032:analysis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL / Q000097:blood; D002914:Chylomicrons / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism; D006949:Hyperlipidemias / Q000209:etiology* / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism*; D007422:Intestines / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008196:Lymph / Q000737:chemistry / Q000378:metabolism; D008297:Male; D019518:Postprandial Period; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002352:Carrier Proteins; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D002914:Chylomicrons; D012333:RNA, Messenger; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D000496:Alloxan; D002784:Cholesterol