1 Division of Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center; and 2 Department of Pathology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267
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ABSTRACT |
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High-fat diets are essential in suckling animals to ensure adequate calories for postnatal growth, but their lymphatic transport of dietary lipids has not been characterized. We established a lymph fistula model in suckling rats to quantify intestinal uptake and lymphatic transport of dietary lipids and analyzed lipoprotein fractions. Suckling 19-day-old Sprague-Dawley rats had their mesenteric lymph ducts cannulated and gastroduodenal tubes inserted. After overnight recovery, [3H]triolein and [14C]cholesterol were infused for 6 h. Of the total dose, only 38% of triolein and 24% of cholesterol were transported in the lymph of suckling rats. Analyses of residual luminal contents and intestinal mucosal homogenate showed neither reduced absorption nor delayed mucosal processing of ingested lipids to be the cause. Thin-layer chromatographic analysis of radioactive mucosal lipids, however, showed a predominance of free fatty acids (60%) and free cholesterol (67%), implying impaired esterification capacity in these animals. We speculate that this reduced esterification allows for portal transport or direct enterocyte metabolism of dietary lipids.
suckling rat; fat absorption; chylomicron; intestinal absorption
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INTRODUCTION |
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THE ABILITY OF THE SUCKLING animal to absorb fat efficiently from its diet is important for postnatal growth since fat is the major source of calories in milk. Human studies suggest that babies absorb dietary fat differently from adults. A study on formula-fed babies suggests that term and preterm infants absorb fat less efficiently than do adults (8). This is surprising, because one would expect better fat absorption in babies compared with adults because of their high-fat diet and higher caloric requirement. These findings, however, are based on fecal fat excretion studies and do not provide any information regarding the absorption rate or the contribution of endogenous lipids to the total amount of lipids secreted by the small intestine. Furthermore, any lipid broken down by bacteria is also included in the fraction of lipid absorbed by the gastrointestinal tract. Consequently, the use of fecal fat excretion as a means to determine intestinal lipid absorption will overestimate the amount of fat absorbed by the small intestine.
Animal studies, which allow more direct measurement of fat absorption and metabolism, have shown more efficient dietary fat absorption and metabolism in suckling rats than in adult rats (7, 10). A comparative study measuring luminal disappearance of [14C]triolein and 14CO2 expiration in suckling and adult rats concluded that the suckling rat absorbs and metabolizes dietary triolein at significantly higher rates than do adult rats (7). The rate of triglyceride secretion by the small intestine into lymph and plasma is also higher than in adult rats (10).
Our knowledge of the ontogeny of the processes involved in lipid absorption is not well characterized. In contrast to adult rats, in which most of the intraluminal hydrolysis of triglycerides occurs in the small intestine by pancreatic lipase, there is considerable triglyceride hydrolysis by lingual lipase in the stomach of the suckling rat (14). Lingual lipase works best with triglycerides rich in medium-chain fatty acids, and milk fat contains significant amounts of medium-chain fatty acids. However, little is known about cellular events that occur after the uptake of lipid digestion products during development, although there are several studies suggesting that intracellular events necessary for lipid absorption are present even in newborn rats (13, 15, 16). The lymphatic transport of dietary lipids in suckling rats is unknown, even though chylomicrons (CMs) and the other lipoprotein fractions have been demonstrated in the lymph of suckling rats (5). Frost et al. (10), using a blocker of lipoprotein clearance from plasma, demonstrated that most of the triglycerides present in plasma of suckling rats arise from intestinal lymphatic secretion rather than hepatic synthesis.
The measurement of intestinal lymph flow and of lipids in lymph is a means to allow direct quantification of intestinal lipid absorption. The mesenteric lymph fistula model has been used extensively by our laboratory as well as others to study intestinal fat absorption in adult rats (21). This model allows one to study lipid absorption in conscious, unanesthetized animals under steady-state conditions in which a constant intraduodenal infusion of lipid results in steady lymphatic transport of the lipid. It also allows direct sampling and analysis of CMs and apolipoproteins secreted by the small intestine before they enter the circulation. There has only been one previous study utilizing this model that attempted to examine lymphatic transport of dietary lipids in suckling rats (10). This study, however, only allowed 45 min of recovery after anesthesia, did not quantify the amount of milk present in the stomach before surgery, and only collected lymph for 3 h. This is in contrast to the usual rat mesenteric lymph fistula model in which rats are allowed to recover overnight to ensure that the anesthesia has worn off and are fed exclusively by a gastroduodenal tube to control and quantify the exact amount of lipid administered and in which lymph is collected for 6-8 h to achieve steady-state lymphatic lipid output, during which time the rat remains fully conscious. The only other study to examine lymphatic lipid composition in suckling rats (6) analyzed pooled lymph from several animals collected at a single time point under anesthesia.
The aims of this study, therefore, were 1) to establish a mesenteric lymph fistula model in suckling rats similar to the established model in adult rats to allow direct measurement of intestinal lipid absorption in suckling rats and 2) to test the hypothesis that the suckling rat, consistent with its high-fat diet, is able to transport dietary lipids into lymph more efficiently than the adult animal. We quantified the uptake and lymphatic transport of both triglyceride and cholesterol in the suckling rat and also characterized the lipoprotein fraction and its apolipoprotein composition in the lymph of suckling rats.
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MATERIALS AND METHODS |
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Animal preparation. Sprague-Dawley rats aged 19 days and weighing 35-45 g were used. The rats were removed from their dams and anesthetized with a mixture of ketamine (40 mg/kg) and xylazine (7.5 mg/kg) intraperitoneally. The main mesenteric lymph duct was cannulated with clear vinyl tubing (0.5-mm OD; Dural Plastics and Engineering, Auburn, Australia) according to the techniques of Bollman et al. (3) in adult rats. Surgery was performed under a dissecting microscope because of the small size of the lymph duct. A polyvinyl chloride tube (0.8-mm OD) was inserted through the fundus of the stomach into the duodenum. A purse-string suture (6-0 silk) and cyanoacrylate glue were used to secure the duodenal infusion tube. The gastroduodenal and lymph duct tubes were externalized through the right flank of the rat to allow easy access for infusion and collection. The skin, abdominal musculature, and peritoneal layers were closed in a single layer (4-0 silk). The rats were kept in restraining cages at an ambient temperature of 30°C and allowed to recover from the anesthesia. Once the animals regained consciousness, 5% glucose in normal saline was infused at 0.3 ml/h during the overnight recovery period to replenish fluid and electrolyte losses due to lymphatic drainage. The infusion rate of 0.3 ml/h was selected because we found that most of the suckling rats had lymph flow rates of ~0.2-0.3 ml/h. Lymph was allowed to drain by gravity into plastic microcentrifuge tubes, and the volume was measured by weighing the tubes before and after lymph collection.
Experimental procedure. The next morning, a lipid emulsion containing 6 µmol of [3H]triolein, 0.78 µmol of [14C]cholesterol, 0.87 µmol of egg phosphatidylcholine, and 5.7 µmol of sodium taurocholate (19 mM) in 0.3 ml of phosphate-buffered saline (pH 6.4) was infused at 0.3 ml/h for 6 h. Lymph was collected 1 h before the lipid infusion (fasting) and then hourly for 6 h. This dose of lipid infused was selected because it was comparable in grams per kilogram of body weight of the suckling rat to doses administered to adult rats (1). Although this lipid dose is equivalent to the daily fat intake of an adult rat, it is less than the daily fat intake of suckling rats since milk has a much higher fat content than rat chow. However, we chose to administer this dose to ensure that our experimental conditions were similar to that of adult rat studies thereby allowing for comparison between the two age groups.
Collection of luminal, mucosal, and liver samples. The animals were anesthetized with the ketamine-xylazine mixture at the end of the 6-h lipid infusion. The duodenum and terminal ileum were tied off to prevent leakage of luminal contents, and the small intestine was excised in one piece. The excised gut lumen was washed three times with 10 mM sodium taurocholate, and the washings were combined and homogenized. The small intestine was then divided into four equal segments and homogenized in 10 mM sodium taurocholate. The entire liver was removed and homogenized in 10 mM sodium taurocholate. Aliquots of lymph, luminal washings, mucosa, and liver were measured for radioactivity by liquid scintillation spectrometry.
Thin-layer chromatographic analyses of mucosal lipids. Lipids from the intestinal mucosal segments were extracted according to the procedure described by Blackenhorn and Ahrens (2). Only the first quarter of the intestine was used for thin-layer chromatographic analyses because most of the residual lipids were in this segment. Samples were plated onto activated silica gel G plates, and the lipids were fractionated using a solvent system of petroleum ether, diethyl ether, and glacial acetic acid (75:15:1.2 vol/vol/vol). Iodine vapor was used to visualize the different lipid classes as well as the comigrating lipid standards. The plates were scraped into scintillation vials, and 1 ml of absolute alcohol was added to help elute the lipids. Radioactivity was then determined after addition of an aqueous miscible scintillant (Opti-Fluor; Packard Instrument, Meriden, CT).
Radioactivity determination. Radioactivity was measured in Opti-Fluor. The samples were counted for 10 min in a liquid scintillation spectrometer (Model TR 1900 tri-carb; Packard).
Preparation of infusate. Appropriate doses of nonradioactive lipids as well as radioactive lipids were mixed, and the solvent was evaporated under a stream of nitrogen. Sodium taurocholate dissolved in phosphate-buffered saline (19 mM, pH 6.4) was added to make up the appropriate concentration, and the mixture was emulsified with a Branson sonicator (model 250/450 sonifier; Branson Ultrasonics, Danbury, CT). Aliquots were taken from the top, middle, and bottom of the emulsion, and its radioactivity was determined by liquid scintillation counting to ensure homogeneity of the lipids in emulsion.
Isolation of lipoproteins. Only fasting lymph and lymph collected during the 4th-6th h of lipid absorption were analyzed. These lymph samples will henceforth be referred to as fasting lymph and fat-infused lymph, respectively. Sequential density ultracentrifugation of lymph samples was accomplished using a Beckman SW 41 Ti rotor at 17°C. The lipoprotein classes separated were: CM (d < 1.006 g/ml, 1.06 × 106 g · min), very low-density lipoprotein (VLDL; d < 1.006 g/ml, 230 × 106 g · min), low-density lipoprotein (LDL; 1.006 g/ml < d < 1.063 g/ml, 268 × 106 g · min), and high-density lipoprotein (HDL; 1.063 g/ml < d < 1.21 g/ml, 469 × 106 g · min). All lipoprotein fractions were dialyzed at 4°C against 0.01% EDTA, 0.02% azide, 0.0001% chloramphenicol, and 0.00005% gentamicin in deionized water with two changes of dialysate. Albumin is usually present with the CMs and can be removed by repeated washing. The additional washing procedures, however, may have resulted in the loss of other apolipoproteins such as apo A-I and apo A-IV and were therefore not performed in this experiment. Fifty micrograms of each lipoprotein fraction were loaded in each lane before SDS-PAGE. The protein molecular standard was supplied by GIBCO BRL (Grand Island, NY). Bands were stained with 0.1% (wt/vol) Coomassie brilliant blue R-250 in methanol-acetic acid-water (5:1:4 vol/vol/vol) and destained in the same solution.
Materials. Triolein, cholesterol, egg phosphatidylcholine, and sodium taurocholate were purchased from Sigma-Aldrich (St. Louis, MO). The radioactive [9,10-3H(N)]triolein and [4-14C]cholesterol were purchased from New England Nuclear (Boston, MA). All solvents and reagents used were of analytical grade. Solvents were used without redistillation.
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RESULTS |
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Lymph flow.
The mean lymph flow rate in 19-day-old suckling rats was relatively
constant throughout the experiment at 0.27 ml/h (range 0.22-0.32
ml/h; Fig. 1). The flow rate remained
unchanged throughout the lipid infusion.
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Recovery of [3H]triolein.
[3H]triolein output into lymph increased during the lipid
infusion to reach a steady output after 2 h (Fig.
2). The maximal hourly lymphatic output
attained was 50% of the hourly infused dose. When expressed as a
percentage of the total dose of lipid infused, the lymphatic
radioactive triolein output was ~38% of the total infused dose (Fig.
3). We then determined the amount of
radioactive triolein recovered from the lumen after 6 h of constant intraduodenal lipid infusion. As shown in Fig. 3, only 1.4%
of the total infused dose was recovered in the intestinal lumen,
indicating that most of the infused radioactive triolein was digested
and absorbed by the small intestine. These data, which showed that the
suckling rat is very efficient at uptake of dietary triolein, were
further supported by the fact that most of the infused radioactive
triolein was recovered from the first quarter of the small intestine
(data not shown). Mucosal recovery, which represents the
[3H]triolein that was taken up by the small intestine and
waiting to be transported out of the small intestine as
triglyceride-rich CMs, was 8% of the total infused dose (Fig. 3).
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Radioactive [14C]cholesterol recovery.
Cholesterol output into lymph increased throughout the lipid infusion
to reach a maximum of 39% of the hourly infused dose at 6 h (Fig.
4). The total recovery of
[14C]cholesterol in the suckling rat at the end of the
experiment was 57% (Fig. 5). Lymph
recovery was only 24% of the total infused dose. Luminal contents and
mucosal radioactivity were analyzed and found to be 6% and 24% of the
total administered dose, respectively. This implies that the low
recovery of our label was not due to poor intestinal uptake or lack of
CM formation within the enterocyte. Cholesterol was recovered in
decreasing amounts from the intestinal segments in a proximal-to-distal
gradient (data not shown). Recovery from the liver again represents a
small fraction of the total dose (2.2%) and does not explain the
discrepancy between infused and recovered radioactivity. Analyses of
the stomach, feces, and urine showed negligible amounts of
radioactivity and, hence, cholesterol.
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Absorptive and transport indices. The absorptive index is defined as the percentage of infused radioactive lipid absorbed by the gastrointestinal tract at the end of the experiment. It is derived by subtracting the percentage of radioactive lipid remaining in the gastrointestinal lumen from 100%. The lymphatic transport index is the percentage of the absorbed lipid that is transported in lymph. This index allows us to assess the ability of the small intestine to transport lipid taken up by the small intestine as triglyceride-rich CMs and VLDL in lymph. In our suckling rats, most of the infused radiolabeled triolein was taken up by the gastrointestinal tract, with an absorptive index of 98.6 ± 0.3%. In contrast, the lymphatic transport index was only 38.3 ± 4.6%. Suckling rats also take up cholesterol extremely well, with an absorptive index of 93.9 ± 1.5%. The transport of absorbed cholesterol into lymph is also significantly lower than expected in the suckling rat (25.4 ± 2.7%). Although the absorptive indices show efficient uptake of dietary fat, the marked discrepancy between absorptive and lymph transport indices suggests other means of transport or utilization of dietary fats by suckling rats.
Thin-layer chromatographic analyses of mucosal lipids. Only 8% of the total infused dose of triglyceride was present in the intestinal mucosa at the end of the 6-h infusion. Most of this was in the form of free fatty acids (60 ± 7%) rather than triglycerides (29 ± 7%). Small proportions of diglycerides (4%) and monoglycerides (5%) were also present. When radioactive cholesterol in the small intestinal mucosa was analyzed, most of the cholesterol present in the mucosa was as free cholesterol (83 ± 3%) and the remaining was as cholesterol esters (17 ± 2%).
Lymph apolipoprotein composition.
The lipoproteins from fasting lymph samples and lymph collected during
fat absorption (4th-6th h) were isolated by density ultracentrifugation and analyzed. The apolipoprotein fractions of lymph
lipoproteins in suckling rats are shown in Fig.
6. Apo A-I, apo A-IV, and apo B-48 were
present in the CM fraction (Fig. 6A). Fat infusion did not
alter apolipoprotein composition of lymph CM. Similar to lymph CM, the
major apolipoproteins present in lymph VLDL were apo A-I, apo A-IV, and
apo B-48 (Fig. 6B). Small amounts of apo E were also present
in CM and VLDL. Fat infusion increased apo A-IV and apo E in lymph
VLDL. In contrast to lymph CM and VLDL, lymph LDL contains both apo
B-48 and apo B-100 in addition to apo A-I, apo E, and apo A-IV (Fig.
6C). Since apo B-100 is normally not made by the rat small
intestine, part of lymph LDL was probably derived by filtration from
the circulation. More apo E was present in lymph LDL than in lymph CM
and VLDL, again corroborating the speculation that plasma filtration of LDL into lymph occurs because apo E is not synthesized by the intestine. Fat infusion increased the quantity of apo A-IV in lymph
LDL. The apolipoprotein fractions of lymph HDL were similar to lymph
LDL, except that apo A-I was the predominant apolipoprotein (Fig.
6D). The apolipoprotein composition of lymph HDL was
unchanged by fat infusion.
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DISCUSSION |
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Our data demonstrated several differences in the way the suckling rat handles dietary lipids compared with the adult rat. These differences were not due to experimental techniques because we created a similar model to that of adult rats, attempting to emulate conditions and lipid dosing so that valid comparisons of intestinal lipid absorption and lymphatic transport of dietary fat between suckling and adult rats could be made. Unlike the adult rat, no lymphagogic response (increase in lymph flow during a lipid infusion; Refs. 4 and 17) was noted in the suckling rat during the lipid infusion. This may be a function of the immaturity of the suckling rat. As a comparison, the postprandial inhibitory control of ingestion after lipid feeding in suckling rats was present postnatally at 15 days but not at 12 days (22). It is therefore conceivable that the lymphagogic effect of lipid feeding develops later, perhaps after weaning. Lymph flow plays an important role in the transport of CMs across the lamina propria into the lacteals (20). Tso et al. (19, 20) proposed that the lymphagogic effect of lipid absorption was to facilitate the transport of CMs across the interstitial matrix into the lymphatics. In adult rats, when the lamina propria is well hydrated at a lymph flow rate of 40 µl/min (2.4 ml/h), lymph flow has little influence on the movement of CMs into the lacteals (19, 20). Assuming that the same criteria can be applied to suckling rats, a lymph flow rate of 0.3 ml/h (our suckling rats weigh ~1/8th of the adult rat) is probably sufficient to adequately hydrate the lamina propria to allow unrestricted movement of CMs into lacteals. This would suggest that the lack of lymphagogic response in suckling rats is unlikely to impair CM secretion into lymph. Also, if lymph flow rate were to impede the flow of CMs into lacteals, there would be accumulation of radioactive lipid in the mucosa. Since this was not seen, it again supports the notion that a lack of lymphagogic response in suckling rats does not impair CM secretion into lymph.
Table 1 shows the differences in
intestinal lipid absorption between our suckling rats and previously
published data from our laboratory on adult rats (1, 18). Our
results confirm previous animal studies showing that the suckling rat
is very efficient at absorbing dietary lipids (7,
10). Surprisingly however, the suckling rat, despite its
high-fat diet, does not transport dietary lipids into lymph as
efficiently as the adult rat. Suckling rats had reduced maximum hourly
lymph output as well as total lymph recovery of
[3H]triolein compared with adult rats under similar
conditions (1). Total recovery of
[3H]triolein at the end of the experiment was also much
lower in suckling rats, with most of the shortfall accounted for by the reduced lymphatic recovery of [3H]triolein in suckling
rats. These findings are very clearly demonstrated when comparing
absorptive and lymph transport indices between suckling and adult rats.
Although little difference is noted in absorptive index, suckling rats
have a much lower lymph transport index than adult rats (38.3% vs.
61.4%) (1). These findings suggest either that the
suckling rat transports dietary triglycerides through alternative means
such as the portal route in addition to the lymphatics or that there is
direct metabolism of dietary fat by the enterocytes.
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The portal transport of long-chain triglycerides is usually insignificant compared with the lymphatic route, except under certain conditions such as reperfusion following an ischemic injury (11). The suckling rat, however, may utilize this route to allow for more rapid transport of dietary lipids into the circulation to target organs. Intermittent portal blood sampling would need to be taken during the experiment, and information regarding portal blood flow would be necessary to test our speculation, but this would be technically difficult to do and the animals would be less likely to survive due to blood loss and the performance of multiple surgical procedures. Although Fernando-Warnakulasuriya et al. (6) analyzed the lipid components of portal blood in 10-day-old rat pups, no attempt was made to measure portal blood flow, making their data in isolation difficult to interpret.
The other possible explanation for the low recovery of triolein in suckling rats may be because of direct metabolism of dietary triglycerides and fatty acids by enterocytes. The data of Flores et al. (7), which used breath tests, demonstrated that triolein disappearance from intestinal lumen and 14CO2 excretion (reflecting triglyceride oxidation) was two to three times higher in suckling rats than in adult rats. Their data confirm more efficient intestinal absorption of dietary fat but also indicate more rapid metabolism. Whether the more rapid metabolism is a result of faster utilization of dietary fat by all target organs or is a result of direct metabolism by enterocytes was not explored. The advantage of direct enterocyte metabolism is that it would allow for very efficient utilization of dietary lipids. Measuring this, however, would be difficult since it would entail utilizing cell cultures from both adult and suckling rat enterocytes and quantifying their metabolism of triolein or cholesterol.
The third possible explanation for the reduced lymphatic recovery may be because of incomplete recovery of intestinal lymph. An accessory mesenteric lymph duct is situated inferior to the main duct and mainly drains lymph from the terminal ileum and colon. Previous experiments in our laboratory on adult animals in which this duct was blocked and in which the thoracic duct was cannulated demonstrated little additional recovery of lipids, making it an unlikely explanation (18).
The predominance of free fatty acids within the proximal intestinal mucosa instead of triglycerides, as found in adult rats (1), implies that the suckling rat may have a compromised ability to esterify absorbed monoglycerides and fatty acids that form triglycerides before lymphatic transport. This was a very interesting but unexpected result since there are two previous studies that have demonstrated the presence of these esterifying enzymes in suckling rats (15, 16). However, a study analyzing the fatty acid content of pooled lymph collected from 10-day-old rat pups found that free fatty acids were present in lymph, a finding not seen in adult rats (6). Up to 3% of the lipids present in lymph were present as free fatty acids. This suggests that reesterification of triglycerides in the intestinal mucosa is impaired in suckling animals. Another possible explanation may be the effect of abdominal surgery and gut handling on the activity of the esterifying enzyme complex. However, our data show no evidence of accumulation of the radioactive triolein within the intestinal mucosa at the end of the lipid infusion in suckling rats compared with the adult rat (Table 1). In the previous study by Fernando-Warnakulasuriya et al. (6), free fatty acids were found in lymph even in the absence of abdominal surgery and bowel handling before lymph collection. These studies suggest that reduced esterification of fatty acids in the intestine of suckling rats is not likely due to previous abdominal surgery. The higher free fatty acid content within the intestinal mucosa of suckling rats compared with adult rats could potentially allow direct absorption of free fatty acid into the portal circulation and, hence, more rapid transport to other organs, thus accounting for lower than expected recovery of radioactive lipid from lymph. We speculate that portal transport of dietary lipids occurs in suckling rats to compensate for the reduced esterification ability of the intestinal mucosa and reduced lymphatic transport of dietary lipids, thereby allowing no reduction in the overall absorption of dietary lipids.
Differences were also noted in the absorption and lymphatic transport of [14C]cholesterol in suckling rats compared with adult rats (Table 1). Although the pattern of lymphatic output is similar, the maximal lymphatic transport of [14C]cholesterol (39% vs. 50% in adult rats) as well as total [14C]cholesterol recovery at the end of the experiment (57% vs. 85% in adult rats) were less in suckling rats compared with adult rats (18). Mucosal recovery, however, was similar regardless of the age of the animal. Again, the main reason for the reduced recovery of cholesterol in the suckling rat is due to reduced lymphatic transport, as evidenced by the significantly reduced transport index (25.4% vs. 41% in adult rat) (18). Unlike adult rats, analyses of residual cholesterol within the intestinal mucosa of suckling rats showed predominance of the free form, suggesting that suckling rats have a problem with reesterification.
The apolipoprotein fractions of lymph CM and VLDL in suckling rats are comparable to those found in adult rats. Similar to the adult rat, only apo B-48 was present in lymph CM and VLDL, implying that apo B editing is intact in baby rats. In contrast to CM and VLDL, lymph LDL contains both forms of apo B, i.e., B-48 and B-100, as well as apo E. Since the intestine only makes apo B-48, the likely explanation for this observation is that lymph LDL is derived partly from the gut and also from plasma through filtration by intestinal capillaries. Our speculation that the gut synthesizes LDL is further supported by the presence of both apo A-I and apo A-IV in addition to the two forms of apo B in lymph LDL. Whether this ability of the gut to synthesize LDL is unique to the suckling rat remains to be demonstrated. Lymph HDL in the suckling rat is an apo A-I-rich particle but also contains apo A-IV and apo B-48. Glickman and co-workers (9, 12) have previously demonstrated that the adult rat intestine secretes HDL. Our data confirms this observation because it shows that the suckling rat intestine is also capable of making HDL. Lipoprotein metabolism in immature animals, however, is an area that is largely unknown, and further studies are indicated.
Our mesenteric lymph fistula suckling rat model has been very useful in contributing to our knowledge of intestinal fat absorption in the immature animal. It has provided information on the efficacy of lymphatic transport of dietary triolein and cholesterol and has demonstrated significant differences in the absorption of dietary lipids compared with adult rats. These differences, which presumably are a result of immaturity of the gastrointestinal system, may be compensated for by the suckling rat's ability to directly utilize nutrients. Further studies on the esterification capacity of the suckling rat and its metabolism of nutrients obviously are indicated because they will further our understanding of nutrient absorption in infancy.
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ACKNOWLEDGEMENTS |
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This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grant PO1-DK-54504.
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FOOTNOTES |
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Address for reprint requests and other correspondence: P. Tso, Dept. of Pathology, Univ. of Cincinnati Medical Center, 231 Bethesda Ave. (ML 0529), Cincinnati, OH 45267 (E-mail: tsopp{at}emailuc.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Received 7 December 1999; accepted in final form 14 March 2000.
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