Lipid and apolipoprotein B48 transport in mesenteric lymph and the effect of hyperphagia on the clearance of chylomicron-like emulsions in insulin-deficient rats.
In insulin-deficient streptozotocin-treated rats the intestine is hypertrophic and cholesterol synthesis and transport from the intestine are increased. The increased load of cholesterol is transported through the mesenteric lymph in chylomicrons. Clearance from plasma of injected chylomicrons is slowed in insulin-deficient rats, but the underlying mechanisms are currently unresolved. Hyperphagia may increase the size of chylomicrons which could contribute to defective chylomicron clearance in insulin-deficiency. In the present experiments we compared the size and number of chylomicrons in mesenteric lymph of control rats and diabetic rats infused with fat at two levels. In control and diabetic lymph-cannulated rats, as the infused dose of lipid increased the transport of triglyceride increased substantially compared with fasted rats. In contrast the transport of apoB48 increased by only a small amount during fat transport. Therefore, increased lipid transport was accomplished mostly by increased particle size, with only small increases in numbers of particles in intestinal lymph. Insulin-deficiency had no effect on triglyceride or apoB48 transport in lymph. Calculations suggested that each chylomicron particle contained a single molecule of apoB48. When hyperphagia in diabetic rats was prevented, the plasma triglycerides were decreased but the slow plasma clearance of injected chylomicron-like emulsions persisted. Hyperphagia, therefore, was unconnected to the impairment in chylomicron metabolism in insulin-deficient rats. Changes in the association with plasma apolipoproteins, in the expression of receptors for uptake of chylomicron remnants or in exposure to endothelial lipases may be responsible for the defective clearance of triacylglycerol-rich lipoproteins.
Martins
I J
IJ
Department of Physiology, University of Western Australia, Nedlands.
Sainsbury
A J
AJ
Mamo
J C
JC
Redgrave
T G
TG
D000042:Absorption; D000818:Animals; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000493:pharmacokinetics; D006963:Hyperphagia / Q000378:metabolism*; D007328:Insulin / Q000172:deficiency*; D050356:Lipid Metabolism; D008196:Lymph / Q000378:metabolism*; D008297:Male; D008643:Mesentery; D051381:Rats; D017208:Rats, Wistar
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002914:Chylomicrons; D005217:Fat Emulsions, Intravenous; D007328:Insulin; D002784:Cholesterol