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 hype rtrophic and cholesterol synthesis and transport from the intestine ar e increased. The increased load of cholesterol is transported through the mesenteric lymph in chylomicrons. Clearance from plasma of injecte d chylomicrons is slowed in insulin-deficient rats, but the underlying mechanisms are currently unresolved. Hyperphagia may increase the siz e of chylomicrons which could contribute to defective chylomicron clea rance in insulin-deficiency. In the present experiments we compared th e size and number of chylomicrons in mesenteric lymph of control rats and diabetic rats infused with fat at two levels. In control and diabe tic 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 a mount during fat transport. Therefore, increased lipid transport was a ccomplished mostly by increased particle size, with only small increas es 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 o f 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 unc onnected to the impairment in chylomicron metabolism in insulin-defici ent rats. Changes in the association with plasma apolipoproteins, in t he expression of receptors for uptake of chylomicron remnants or in ex posure to endothelial lipases may be responsible for the defective cle arance of triacylglycerol-rich lipoproteins.