Stimulation of intestinal apolipoprotein A-IV by lipid is independent of capsaicin-sensitive afferent signals

We tested the hypothesis that stimulation of synthesis and secretion of intestinal apolipoprotein A-IV (apo A-IV) by intestinally infused lipid is mediated by capsaicin-sensitive afferent signals. Vehicle or capsaicin (125 mg/kg) was systemically administered to rats; then the effects of intestinal infusion of lipid emulsions on lymph lipid and apo A-IV transport were determined in rats equipped with duodenal infusion cannulas and mesenteric lymph fistulas. Capsaicin treatment did not significantly affect lymph outputs of triglyceride, phospholipid, and apo A-IV during duodenal infusion of triglyceride emulsion. In separate studies the effect of capsaicin treatment on ileal lipid-elicited stimulation of intestinal mucosal apo A-IV synthesis was also examined. Ileal lipid infusion increased apo A-IV synthesis in distal ileum, proximal jejunum, and jejunal Thirty-Vella fistulas; this finding was unaffected by capsaicin pretreatment. However, capsaicin treatment significantly attenuated the inhibitory effects of duodenal acid and fat on gastric emptying. These results do not support a role for capsaicin-sensitive, sensory afferent nerves in the stimulation of intestinal apo A-IV by dietary lipid.

Ornithine decarboxylase is involved in repair of small intestine after ischemia-reperfusion in rats

To assess whether ornithine decarboxylase (ODC) is involved in mucosal repair after ischemia-reperfusion (I/R), two approaches were used: 1) measurement of mucosal ODC activity at different intervals after I/R, and 2) inhibition of ODC activity with alpha-difluoromethylornithine (DFMO, an irreversible inhibitor). In the first series of experiments, rats were allowed to recover after superior mesenteric arterial occlusion (10 min) before harvesting the intestinal mucosa for measurement of ODC activity. ODC activity increased markedly 6 h after I/R, and greater than 72 h were required for enzyme activity to return to normal. DFMO treatment completely abolished the I/R-induced increase in ODC activity. In another series of experiments, rats with an intestinal lymph fistula were infused intraduodenally at 3 ml/h with vehicle or 2% DFMO in vehicle immediately after I/R. Lipid absorption was measured at 24 and 48 h after I/R. In the DFMO group, lymph radioactive lipid output at 24 h after I/R was significantly lower compared with time-matched sham-operated controls. Lymph lipid output in rats receiving the vehicle was restored to a normal level at 48 h after I/R. However, this restoration of normal lymphatic lipid transport at 48 h I/R was not observed in the DFMO group. These observations indicate that ODC activity plays an important role in the repair process that results in complete restoration of mucosal function 2 days after I/R.

Endotoxemia produces an increase in arterial but not venous lipid peroxides in sheep

Our purpose was to determine the effect of an endotoxin-induced lung injury on circulating lipid peroxides. We measured both malondialdehyde (MDA) and conjugated dienes (as optical density at 233 nm) in aortic and venous plasma and lung lymph in 10 unanesthetized sheep given 1 microgram/kg of Escherichia coli endotoxin. Total lipids and prostanoids 6-ketoprostaglandin F1 alpha and thromboxane B2 were also measured. Six control sheep were also studied. Animals were monitored for a 12-h period and then killed, and lung tissue MDA was determined. A two-phase endotoxin response was noted with an initial pulmonary hypertension followed by a steady-state increase in protein-rich lung lymph flow (QL) between a 3- and 6-h period. Aortic plasma MDA was significantly increased from a base line of 4.8 +/- 1.4 to 8.9 +/- 1.6 and 7.5 +/- 1.3 nmol/ml at 1 and 4 h post-endotoxin. Aortic plasma conjugated dienes increased in all 10 sheep post-endotoxin. Venous levels of both MDA and conjugated dienes were not significantly increased. Lung QL increased two- to three-fold. Lung lymph MDA increased significantly at 1 h post-endotoxin. Lymph conjugated dienes decreased. Plasma and lymph lipid peroxide levels returned to base line by 12 h in most animals. However, tissue MDA remained significantly increased in all sheep from base line of 45 +/- 9 to 85 +/- 14 nmol/g tissue. We conclude that both MDA and conjugated dienes are transiently released into aortic plasma during endotoxin-induced oxidant lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of lymphatics in removal of sheep lung surfactant lipid

To study the role of lung lymphatics in the removal of surfactant lipid from the sheep lung, we injected [1–14C]palmitate intravenously into six animals previously fitted with a cannula draining the caudal mediastinal lymph node. Lung lymph was collected for 100 h after injection of radiolabel. We obtained alveolar lavage material through a tracheostomy in four other animals after intravenous injection of [9,10–3H]palmitate. We measured radioactivity at several time points in lipid extracts from lymph, lavage fluid, and lung tissue. Alveolar lavage disaturated phosphatidylcholine (DSPC) specific activity peaked at about 40 h and was reduced to 30% of this value by 82 h. About 2% of the injected radiolabel was incorporated into lung tissue lipids. Only 4% of the level of labeling achieved in lung tissue lipids was found in lung lymph lipid during 100 h of lymph collection. Sixty-three percent of radiolabel in lymph lipid was recovered in phospholipids, and 29% of phospholipid radiolabel was found in DSPC. The distribution of phosphorus and palmitate radiolabel in lung lymph phospholipid did not closely resemble that of surfactant lipid. No rise in lung lymph DSPC specific activity was observed following the peak in lavage specific activity. If surfactant lipid is removed from the alveolar compartment without extensive recycling, then we conclude that the lung lymphatics do not play a major role in the clearance of surfactant lipid from the alveolar surface.

LYMPHATIC ABSORPTION OF CHOLESTEROL IN THE DOG FOLLOWING CORN OIL AND BUTTERFAT FEEDING

Lymphatic absorption of cholesterol was determined in 11 unanaesthetized dogs with thoracic duct bypasses or fistulae, following the administration of corn oil or butterfat with and without cholesterol supplementation. Comparisons based on fixed amounts of lymph or total lymph lipid, as well as the estimated overall sterol recoveries, showed that the conclusions can vary depending on how the calculations are done. On the basis of data collected in the same animal, it was concluded that the glyceride type of dietary fat had no significant effect on lymphatic absorption of cholesterol in the dog. The feeding of butterfat, corn and coconut oils, or simple triglycerides to different animals resulted in widely varying lymph cholesterol levels, which could not be correlated with any of the variables under direct experimental control.

Role of phospholipids in lymphatic transport of dietary lipids in the dog

The phospholipids of lymph have been measured in relation to the total lipid in 16 chronic thoracic duct fistula dogs during the postabsorptive state and following the administration of various lipid types in the diet. It was found that phospholipid transport related linearly to total lipid transport under all conditions studied, including the postabsorptive state. The percentage of lymph lipid transported as phospholipid ranged from 3 to 18% and was independent of the type of lipid fed. Depriving the animals of phospholipid precursors in the diet for as long as 90 days previously failed to alter this relationship or the total quantity of lipid transported. The total quantity of phospholipid which could be considered as having been newly synthesized as a direct result of processes underlying absorption of exogenous (dietary) fats was small and probably insignificant. The conclusion is reached that phospholipids probably do not serve as intermediates in the absorptive process, nor do they constitute important vehicles for fatty acid transport in lymph.