Lipid and apolipoprotein B48 transport in mesenteric lymph and the effect of hyperphagia on the clearance of chylomicron-like emulsions in insulin-deficient rats

Abstract

SummaryIn 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. [Diabetologia (1994) 37: 238-246]

Obesity and post-prandial lipid metabolism. Feast or famine?

“…The down regulation of LDLr expression may lead to a delay in CR clearance. The food intake of obese mice and diabetic rats consuming food freely (fed ad libitum) has been shown to be markedly increased [35,123]. Prevention of hyperphagia in Zucker obese rats by pair-feeding to lean controls increased longevity [124].…”

“…In Zucker obese rats and strepotozotocin induced rats the clearance of CR has been shown to be delayed [123,129]. In lymph duct cannulated streptozotocin-diabetic rats the number and size of CM produced by the intestine was not found to be different from control rats indicating that the slow clearance of CR may be related to a defect in CR removal by the liver [123].…”

“…The increased transport of dietary fat following a meal is thought to be accommodated by an increase in size of the chylomicron particles rather than number in rats [123] and humans [127]. In diabetic rats and mice the intestine is hypertrophic and cholesterol synthesis and transport from the intestine has been shown to be increased [76,128].…”

Antihyperlipidemic effect of Cyclocarya paliurus (Batal.) Iljinskaja extract and inhibition of apolipoprotein B48 overproduction in hyperlipidemic mice

“…ApoB48 is synthesized by bound ribosomes in the rough endoplasmic reticulum of enterocytes and participates in the assembly process of lipoproteins (Cartwright and Higgins, 2001). The content of apoB48 determines the number of intestinal triglyceride-rich lipoprotein (TRL) particles (Cohn et al, 1993) and each chylomicron contains a single apoB molecule (Martins et al, 1994). There is increasing evidence to show that intestinally derived apoB48-containing lipoproteins play active roles in the atherosclerotic plaque formation (Ginsberg, 2002;Karpe, 1999).…”

Apolipoprotein B-48

“…CM particles contain apoB-48 as a structural protein, which is formed exclusively in the intestine after tissue-specific editing of apoB-100 mRNA in humans [37]. It appears that apoB-48-containing particles are continuously secreted from the enterocyte, and at times of excessive TG availability, lipid droplets fuse with nascent lipoprotein particles, resulting in secretion of very large CM [38]. Once the CM particle reaches the lymphatic space and then the plasma compartment, apoA-I dissociates very rapidly [39] and CM acquires apoC, in particular apoC-II, to enable efficient unloading of its massive TG content after binding to the LPL in the endothelial space [40].…”