Feeding a polyunsaturated fatty acid diet prevents the age-associated decline in glucose uptake observed in rats fed a saturated diet.

The ability of the intestine to adapt to changes in environmental stimuli may be compromised with aging. Young animals fed saturated fatty acids (SFA) versus polyunsaturated fatty acids (PUFA) have an increased intestinal uptake of glucose. The objectives of this study were to determine (1) the effects of age on glucose uptake in rats; (2) the influence of feeding SFA versus PUFA; and (3) the mechanisms of these age- and diet-associated changes. Male Fischer 344 rats aged 1, 9 and 24 months received semi-purified isocaloric diets enriched with either SFA or PUFA. The uptake of 14C-labelled D-glucose was determined in vitro using the intestinal sheet method. Northern blotting, Western blotting and immunohistochemistry were used to determine the effects of age and diet on SGLT1, GLUT2 and Na(+)K(+)-ATPase. The mucosal surface area of the jejunum was reduced in 9 and 24 as compared with 1-month-old rats fed SFA. PUFA delayed this age-associated reduction in surface area. In SFA, the ileal uptake of glucose fell with age when expressed on the basis of intestinal or mucosal weight. Feeding PUFA prevented this decline. Alterations in glucose uptake were not paralleled by the changes in SGLT1, GLUT2 or Na(+)K(+)-ATPase abundance.

Nutritional effects of surgical and medical treatment for short bowel syndrome.

BACKGROUND: The choice of treatment options in short bowel syndrome (SBS) is hampered by a lack of comparative studies. This study uses a previously validated juvenile pig model of SBS to compare nontreated controls (C), surgical treatment with either proximal colon interposition (CI) or bowel lengthening (BL), with medical treatment with codeine and cimetidine (M). METHODS: Treatment was initiated 6 weeks after resection of 75% of the small bowel, and animals were followed until sacrifice at week 16. Feed intake and weight gain were monitored throughout; in vivo nutrient absorption, in vitro nutrient transport, sodium-glucose cotransporter activity, and intestinal morphology (gross and microscopic) were examined at the end of treatment. RESULTS: BL and M treatments resulted in improved rates of weight gain; this improvement was associated with improved absorption of dietary fat. The treatments did not affect carbohydrate or protein absorption in vivo. In vitro fatty acid absorption was not increased in any group. Active uptake of glucose was increased in the colon interposition group, but phlorizin binding (reflecting sodium glucose cotransporter activity) did not differ between groups. Gross serosal and microscopic mucosal surface areas increased in all groups; however, there were no significant differences between the treatment groups. CONCLUSIONS: These results demonstrate that bowel lengthening and medical treatment improved the rate of weight gain in this model of SBS. This appeared to be due to improvement in the absorption of dietary fat, which was not caused by alterations in in vitro uptake or mucosal surface area, suggesting these treatments have their affects by altering motility or intraluminal digestion. These findings suggest that these treatments are worthy of further study in treating patients (primary pediatric) with SBS.

Small bowel review: normal physiology part 1.

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein-mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand.

Intravenous fish oil emulsion attenuates total parenteral nutrition-induced cholestasis in newborn piglets.

Total parenteral nutrition (TPN) causes intrahepatic cholestasis and membrane phospholipid changes. Fatty acid (FA) composition of bile and hepatocyte phospholipid is influenced by dietary FA composition. We hypothesized that altering FA composition of i.v. lipid emulsions modifies 1) severity of TPN-induced cholestasis; 2) hepatocyte membrane composition and function; 3) bile flow and composition. Newborn piglets received either sow's milk, TPN with i.v. soybean oil or TPN with i.v. fish oil (FO). After 3 wk, basal and stimulated bile flow were measured after bolus injections of 20, 50, and 100 micromol/kg of taurocholate (TCA). Bile was analyzed for bile acids, cholesterol, phospholipids, and phospholipid-FA. Sinusoidal and canalicular membrane PL-FA, fluidity, and Na+/K+-ATPase were measured. Although the soybean oil-fed animals developed cholestasis, the FO and milk group had similar liver and serum bilirubin. Basal and stimulated bile flow rates were impaired in the soybean oil but not in the FO group. Hepatocyte membrane FA composition reflected dietary FA. Changes in sinusoidal and canalicular membrane fluidity and sinusoidal Na+/K+-ATPase activity did not explain the effect of FO on TPN-induced cholestasis. Intravenous FO reduces TPN-induced cholestasis by unknown mechanisms.

Oral administration of rapamycin and cyclosporine differentially alter intestinal function in rabbits.

The immunosuppressive drugs rapamycin (Rap) and cyclosporine A (CsA) are used clinically to modify or abolish immune-mediated functions. This study examined the effect of orally administered regimens of Rap, CsA, and a combination of Rap/CsA on intestinal function in male New Zealand white rabbits. Animals received oral doses of CsA (15 mg/kg/body weight/day), low-dose (LD) and high-dose (HD) Rap (0.25 or 1 mg/kg/body wt/day, respectively), or Rap/CsA (0.25 and 5 mg/kg/body wt/day, or 0.5 and 5 mg/kg/body wt/day, respectively) for 20 days. We measured in vitro uptake of nutrients and permeability, and morphometric measurements in the jejunum and ileum were made. Animals receiving HD-Rap or HD-Rap/CsA had decreased food intake, body weight, and intestinal weight, when compared with LD-Rap, LD-Rap/CsA, CsA, or controls. The maximal transport rate (Vmax) for the active jejunal uptake of D-glucose was increased in HD-Rap and CsA, but not in the HD-Rap/CsA-treated animals. The jejunal Vmax of D-glucose in the LD-Rap- or -Rap/CsA-treated animals was no different from controls. In the HD-Rap- and HD-Rap/ CsA-treated animals, jejunal rates of uptake of stearic, linoleic, and linolenic acids were reduced when compared with controls. Jejunal and ileal permeability (as assessed by the passive uptake of L-glucose, tissue conductance, and mucosal-to-serosal flux of [3H]inulin) was increased in animals treated with HD-Rap or HD-Rap/CsA, when compared with CsA or controls. These parameters of permeability were no different at lower doses of Rap or Rap/CsA. The jejunal and ileal villous surface area was increased in CsA, but decreased in HD-Rap or HD-Rap/CsA animals. Thus, HD-Rap given alone or in combination with CsA reduced body weight gain, in part due to reduced food intake and malabsorption of lipids, which was due at least in part to reduced intestinal surface area. The relevance of these findings to patients undergoing chronic immunosuppressive drug therapy needs to be established.

Early dietary experience influences ontogeny of intestine in response to dietary lipid changes in later life.

This study was undertaken to test the hypothesis that a change in the mother's diet at the time of birth and continued during suckling modifies the intestinal transport of nutrients in the suckling offspring. Pregnant rat dams were fed one of four semisynthetic diets during pregnancy [high or low n-6/n-3 diet or a diet enriched with arachidonic acid (AA) or docosahexaenoic acid (DHA)] and were fed the same diet at the time of birth or switched to another diet. The greatest body weight gain was in the suckling rats (15-16 days of age) fed a low n-6/n-3 diet. Switching from this diet caused weight loss, and the observed weight gain with the low n-6/n-3 diet was prevented by previous exposure of the mother to the high n-6/n-3 diet or the AA- or DHA-containing diet. Although continuous feeding of a high n-6/n-3 diet to the mother during pregnancy and lactation was associated with the lowest in vitro rates of fructose uptake, switching the mother to another diet during lactation did not necessarily correct the low absorption. In contrast, continuous feeding of a high n-6/n-3 diet to the mother during pregnancy and lactation is associated with the highest maximal transport rate of glucose uptake into the jejunum and ileum. Jejunal uptake of fatty acids 12:0, 18:0, 18:3(n-3), and cholesterol was less with the low n-6/n-3 diet compared with the high n-6/n-3 diet, whereas the ileal uptake of 18:0 and 18:3(n-3) was higher with the low n-6/n-3 diet. Thus the ontogeny of the intestine is critically influenced by the mother's diet during gestation as well as during the nursing period. Some of the diet-associated changes in nutrient uptake resulting from the mother's diet during pregnancy could be corrected by dietary interventions introduced after birth.

A physiological level of rhubarb fiber increases proglucagon gene expression and modulates intestinal glucose uptake in rats.

Previous work demonstrated that a high fiber diet upregulates proglucagon mRNA and secretion of glucagon-like peptide-1 [GLP-1(7-37)] and insulin compared with an elemental fiber-free diet. This study examined whether similar intakes of fibers differing in physiochemical and fermentative properties alter the expression of intestinal hormones and intestinal absorptive properties. Sprague-Dawley rats were fed either a 50 g/kg cellulose or rhubarb fiber diet for 14 d. Ileal proglucagon mRNA levels were significantly higher in rats fed rhubarb fiber than in those fed cellulose fiber (9.3 +/- 0.9 vs. 6.2 +/- 1.0 densitometer units). Proglucagon mRNA in the colon did not differ between diet treatments. Plasma c-peptide concentrations were significantly higher 30 min after an oral glucose tolerance test in the rhubarb vs. cellulose group (1627 +/- 67 vs. 1290 +/- 71 pmol/L). Passive permeability, measured by the uptake of L-glucose, was significantly higher in the jejunum of rats fed cellulose compared with those fed rhubarb fiber. Adjusting total glucose uptake for passive permeability and unstirred water layer resistance resulted in a higher Km being calculated for the jejunum and ileum of the cellulose fiber group. Jejunal and ileal carrier-mediated uptakes (Vmax) were not altered by diet and reflected the lack of difference between groups in sodium-dependent glucose cotransporter (SGLT-1) and sodium-independent glucose transporter (GLUT2) mRNA levels. Replacing cellulose fiber with rhubarb fiber in a diet upregulated ileal proglucagon mRNA and resulted in a reduced passive permeability but did not affect glucose transport of the small intestine. This work establishes the importance of dietary fiber fermentability in modulating intestinal proglucagon expression and possibly glucose homeostasis.

Ontogeny of intestinal adaptation in rats in response to isocaloric changes in dietary lipids.

Alterations in dietary lipids of the nursing mother result in variations in the lipid content of her milk. Maternal rats, weanlings, and 10-wk-old animals were fed chow or a semisynthetic isocaloric diet enriched with either saturated fatty acids (S) or polyunsaturated fatty acids (P). The jejunal and ileal in vitro uptake of varying concentrations (4-64 mM) of D-glucose and D-fructose or single concentrations of medium- and long-chain fatty acids and cholesterol were assessed in 18- to 21-day-old suckling rats, in 5-wk-old weanling animals, and in 12-wk-old young adults. The rate of uptake of D-glucose and D-fructose was unaffected in suckling rats by changing the lipid content of the diet of the nursing dams, whereas sugar uptake was greater in weanlings or adults fed S compared with P. The jejunal uptake of long-chain fatty acids was not influenced in suckling by changing the mother's diet, whereas in weanlings the uptake of 18:0 and 18:3 was higher with feeding S vs. P. In summary, jejunal uptake of cholesterol was greater in sucklings than in weanlings fed S vs. P. In suckling animals there are different adaptive patterns between the jejunum and the ileum and varying patterns of adaptation in response to alterations in the lipids in the diet when comparing suckling vs. weanling rats. These differences in nutrient uptake could not be explained by age- or diet-associated alterations in villus height. It is concluded that the age of the rat influences the intestinal adaptation of nutrient transport, which occurs in response to changes in dietary lipids, and dietary lipids fed to nursing dams and their offspring are important in the development of the intestine.

Dietary lipids influence the activity of delta 5-desaturase and phospholipid fatty acids in rat enterocyte microsomal membranes.

Previous studies have shown that isocaloric modifications in the type of lipids in the diet alter the nutrient uptake and lipid composition of the intestinal brush border membrane. In this study adult rats were fed for 2 weeks isocaloric semisynthetic diets with triglycerides enriched with either saturated (S) or polyunsaturated (P) fatty acids. Enterocyte microsomal membranes (EMMs) were isolated from along the jejunal villus. The activity of delta 5-desaturase was higher in the upper than in the lower portions of the villus, and was greater in P than in S. The activity of delta 9- and delta 6-desaturases did not vary along the villus or with changes in dietary S or P. The two predominant EMM phospholipids were phosphatidylcholine and phosphatidylethanolamine, and these did not vary along the villus or with changes in diet. The major EMM fatty acids in phosphatidylcholine and phosphatidylethanolamine were 16:0, 18:0, 18:2 omega 6, and 20:4 omega 6; none of the individual fatty acids varied along the villus or with diet, although minor changes in fatty acid classes were observed. Thus, alterations in dietary lipids modify the activity of delta 5-desaturase in the EMMs collected from the upper portion of the villus, but this does not result in the expected changes in fatty acids in the EMM phospholipids.

Polyunsaturated fat in the diet may improve intestinal function in patients with Crohn's disease.

To investigate the effect of increasing dietary polyunsaturated fat intake on fat absorption in Crohn's patients, normal subjects and subjects with inactive Crohn's disease consumed a high polyunsaturated to saturated fat ratio diet. Subjects participated in breath tests before and after six months of a high polyunsaturated to saturated (P/S) fat ratio diet to measure their response to [1-13C] 10:0 and [1-13C] 16:0 ingested with a test meal. Whole body absorption-oxidation of C10:0 was not affected by the diet treatment. Before diet treatment, whole body absorption-oxidation of C16:0 in Crohn's patients was 80% of that observed for control subjects. After consuming a high polyunsaturated to saturated fatty acid ratio diet, subjects increased oxidation of C16:0 by 85% compared to before the diet treatment period. It is concluded that (1) absorption of labelled C16:0 from a test meal is reduced in Crohn's patients, and (2) consumption of a high polyunsaturated to saturated fatty acid ratio diet improves the utilization of dietary C16:0 by Crohn's patients.

Short-chain fatty acid-supplemented total parenteral nutrition enhances functional adaptation to intestinal resection in rats.

BACKGROUND & AIMS: Intestinal adaptation is a complex physiological process that is not completely understood. Total parenteral nutrition (TPN) induces intestinal atrophy that is prevented by the systemic administration of short-chain fatty acids (SCFAs) as measured by morphological indices (i.e., mucosal weight and mucosal DNA, RNA, and protein concentration). The aim of this study was to examine the effect of SCFA-supplemented TPN on functional markers of intestinal adaptation. METHODS: Forty-eight male Sprague-Dawley rats underwent an 80% jejunoileal resection and jugular catheterization. Rats received standard TPN or an isoenergetic, isonitrogenous TPN supplemented with SCFA (TPN + SCFA). Animals were further randomized to receive nutrient solutions for 3 or 7 days. RESULTS: Ileal uptakes of D-glucose were higher (P < 0.05) in both TPN + SCFA groups. Expression of glucose transporter (GLUT)2 messenger RNA (mRNA) was higher (P < 0.007) in the TPN + SCFA group at day 3. Expression of sodium-dependent glucose transporter 1 tended to be higher in both TPN + SCFA groups (P = 0.1). Na+,K+-adenosine triphosphatase mRNA was significantly more abundant in the TPN groups. GLUT5 and sucrase-isomaltase mRNA abundance did not differ between groups. CONCLUSIONS: Intravenous SCFAs facilitate intestinal adaptation after resection by increasing basolateral intestinal nutrient transport. The addition of SCFAs to current TPN formulations may be warranted to improve functional characteristics of the gastrointestinal tract.

Inhibition of lipid absorption as an approach to the treatment of obesity.

A reduction in fat intake may be achieved by making educated choices to reduce total calorie intake, to consume a lower quantity of total fats, or to modify the ratio of saturated-to-polyunsaturated lipids. Leptin agonists or NPY or CCK antagonists may prove to be useful to diminish appetite and thereby reduce the total intake of food. But eating has such cultural, social, and hedonistic attributes that such a single-pronged approach is unlikely to be successful. The use of fat substitutes may prove to be popular to provide a wide range of snack food options, but these are likely to be of minimal use in weight reduction programs because of their distribution of additives in only a limited number of foods. The inhibitors of lipid digestion will be modestly successful in the short term; their long-term success will be influenced by gastrointestinal adverse effects and the need to consume fat-soluble vitamin supplements to prevent the development of fat-soluble vitamin deficiencies. The inhibition of lipid absorption is an attractive targeted approach for the treatment of obesity, since this would reduce the uptake of visible as well as invisible fats, which would potentially offer convenient dosing, and could also be a means to inhibit secondarily the uptake of carbohydrate calories.

A high cholesterol diet blocks the effect of calcium channel blockers on the uptake of sugars in rabbit intestine.

Two classes of calcium channel blockers, nisoldipine (NIS) and verapamil (VER), alter the intestinal uptake of sugars, and varying the lipid composition of the diet also modifies intestinal transport function. This study was undertaken in adult male New Zealand rabbits to assess the effect of 3 weeks of dosing with NIS (1 mg.kg-1.day-1) or VER (4 mg.kg-1.day-1) on the in vitro jejunal uptake of D-galactose and L- or D-glucose. The value of the maximal transport rate of D-galactose (Vmax) increased with NIS and VER, compared with control vehicle. The value of the apparent Michaelis constant (K(m)) rose with NIS and fell with VER, and the value of the passive permeability coefficient (Pd) estimated from the uptake of L-glucose fell with NIS and rose with VER. These effects of NIS and VER on Vmax, K(m), and Pd were prevented by feeding a high cholesterol (2.8%) supplemented chow diet (HCD), as compared with chow alone. These effects were not due to any change in the animal's weight gain or intestinal mucosal surface area. The acute exposure of the jejunal tissue in vitro to varying concentrations of NIS but not VER reduced the uptake of D-glucose but had no effect on basal short circuit current (Isc) in either chow or HCD. Isc stimulated with glucose or theophylline was less in chow-fed rabbits compared with HCD-fed rabbits given NIS or VER. Thus, the active transport of sugars by the sodium-dependent transporter in the brush-border membrane, SGLT1, and the passive uptake by the paracellular route are variably influenced by these two classes of calcium channel blockers, and this effect is modified by the cholesterol content of the diet.

Short-chain fatty acids increase proglucagon and ornithine decarboxylase messenger RNAs after intestinal resection in rats.

BACKGROUND: Intestinal adaptation is a complex physiological process that is not completely understood. Systemic administration of short-chain fatty acids (SCFAs) has been shown to facilitate adaptation to small bowel resection; however the mechanisms underlying this phenomena are unknown. METHODS: Forty-six male Sprague-Dawley rats underwent an 80% jejunoileal resection and jugular catheterization. After surgery, rats were randomly assigned to receive standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous TPN supplemented with SCFAs. On day 3 or 7 after surgery, ileal samples were removed for determination of mucosal wet weight, DNA, RNA, and protein concentrations. Total cellular RNA was extracted for use in Northern blot analysis to quantify proglucagon and ornithine decarboxylase messenger RNAs (mRNAs). RESULTS: Total, mucosal, and submucosal weights were increased (p < .05) in the SCFA group both 3 and 7 days after surgery. Ileal DNA and RNA concentrations were increased (p < .05) in the SCFA group at both time points; however ileal protein concentration did not differ between groups until 7 days after resection. Levels of proglucagon and ornithine decarboxylase messenger RNAs were higher (p < .05) in the SCFA group at both time points. CONCLUSION: The upregulation of proglucagon and ornithine decarboxylase gene expression may be the mechanism by which SCFAs facilitate intestinal adaptation.

Ileal recovery of nutrients and mucin in humans fed total enteral formulas supplemented with soy fiber.

The objective of this study was to determine whether soy fiber supplementation of total enteral nutrition formulas affected small intestinal recovery of nitrogen, amino acids, and carbohydrates or mucin output in eight human subjects (four males, four females) with ileostomies. The subjects ingested five test diets to provide 1.0-16.5 g soy fiber/L for 2 consecutive days each. The five test diets, each with a different soy fiber content were formulated by varying the relative proportion (1:0, 0.75:0.25, 0.5:0.5, 0.25:0.75, and 0:1) of two commercially available formulas. Effluent dry matter increased with soy fiber intake as a result of the quantitative recovery of soy fiber nonstarch polysaccharide. Nitrogen and amino acid digestibilities were unchanged by the ingestion of soy fiber. Nutrients from the total enteral nutrition formulas were well digested in the small intestine with true nitrogen and amino acid digestibilities in excess of 90% and starch digestibilities approaching 100%. Ileal mucin output was higher in male subjects and was unaffected by soy fiber intake. In summary, soy fiber supplementation does not compromise protein and carbohydrate absorption from the small intestine of humans.

Intestinal morphology and transport after ileal resection in rat is modified by dietary fatty acids.

The authors tested the hypothesis that the intestinal morphology and uptake of nutrients after resection of the distal half of the small intestine of rats responds to alterations in the dietary content of saturated (SFA) and polyunsaturated (PUFA) fatty acids. Adult female Sprague-Dawley rats were subjected to a sham operation or to the surgical resection of the distal half of the small intestine, leaving the ileocecal valve intact. The animals were fed chow for 3 weeks, then either chow or isocaloric semisynthetic SFA or PUFA diets for a further 2 weeks. Food consumption, weight gain and jejunal mucosal surface area were unchanged after ileal resection. A microdensitometric autoradiographic technique was used to examine the distribution of 3H-leucine and 3H-lysine along the villus: approximately 70% of uptake occurred in the upper 30% of the enterocytes of the villus in chow-fed rats, and this portion was unchanged by ileal resection. The jejunal uptake of 40 mM of glucose, observed in vitro, was twice as high in animals that had undergone resection and were fed SFA than in those fed PUFA. In summary, (1) there is a separation between the adaptation of intestinal transport function and dynamic/static morphology after ileal resection, and (2) glucose uptake after ileal resection is enhanced by SFA in the diet and is not explained by any changes in the animals' food intake, weight gain or intestinal morphology.

Dietary omega 3 fatty acids and cholesterol modify enterocyte microsomal membrane phospholipids, cholesterol content and phospholipid enzyme activities in diabetic rats.

Diabetes-associated changes in intestinal uptake of nutrients are modified by isocaloric variations in the type of dietary lipids, and are associated with alterations in the phospholipid and fatty acyl content of the intestinal brush border membrane. The present study was designed to test the hypothesis that diet- and diabetes-associated changes in enterocyte microsomal membrane phospholipids are due to variations in the activity of two phospholipid metabolizing enzymes, 1,2-diacylglycerol:CDPcholine cholinephosphotransferase (CPT) and phosphatidylethanolamine methyltransferase (PEMT). Adult female Wistar rats were fed one of four semisynthetic diets--beef tallow low in cholesterol (BT), beef tallow high in cholesterol (BTC), fish oil low in cholesterol (FO) or fish oil high in cholesterol. In half of the animals, diabetes mellitus was produced by injection of streptozotocin. Jejunal and ileal enterocyte microsomes (EMM) were isolated and analyzed for cholesterol and phospholipids, as well as for CPT and PEMT activities. In control animals, feeding FO reduced EMM total phospholipids including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol. Feeding FO resulted in a greater than 95% reduction in the activity of CPT. Diabetes was associated with increased jejunal EMM total phospholipids including sphingomyelin (SM) and PE, without associated changes in CPT or PEMT. Dietary cholesterol supplementation did not affect EMM total cholesterol or phosphlipid composition in control rats fed BT or FO, but was associated with an increase in EMM cholesterol in diabetic rats fed BT or FO. A decrease in total phospholipids due to a decline in SM, PC and PE in diabetic rats fed FO was not associated with changes in the activities of CPT or PEMT in EMM.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of isradipine on the formation and regression of fatty streaks in cholesterol fed rabbits.

OBJECTIVE: The aim was to determine whether the antiatherogenic effect of the calcium channel blocker isradipine on fatty streak formation was dependent upon a temporal relationship between cholesterol feeding and administration of the drug. METHODS: The study was done in New Zealand White rabbits fed a diet supplemented with cholesterol (2.5% w/w) for three weeks. Such a regimen results in loss of endothelium dependent relaxation and accumulation of cholesterol in the aorta four weeks later. The calcium antagonist isradipine was given in a dose of 0.25 mg.kg-1.d-1 at specified periods during the study to seven subgroups of animals: (1) standard diet + 2.5% cholesterol for three weeks; (2) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks; (3) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks; (4) standard diet + 2.5% cholesterol+isradipine for three weeks followed by standard diet alone for four weeks; (5) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given throughout the seven weeks; (6) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given during the final four weeks only; (7) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks with isradipine given during the final eight weeks. Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation to acetylcholine and the calcium ionophore A23187, and relaxant responses to sodium nitrite. Serum was collected for measurement of cholesterol and triglyceride concentration. RESULTS: When isradipine was given either during cholesterol feeding and continued for four weeks following it (subgroup 5) or during the four weeks following cholesterol feeding (subgroup 6), loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta was prevented. However, administration of isradipine during the period of cholesterol feeding alone (subgroup 4) was without effect. Also, administration of isradipine after lesions of fatty acid streak type were established appeared to have a favourable effect on removal of cholesterol from the aorta. CONCLUSIONS: Isradipine protects against the development of fatty streaks in rabbits fed a diet supplemented with 2.5% cholesterol. Administration of this drug after fatty streaks are formed also promotes their resolution.

Feeding an isocaloric omega-3 fatty acid diet reduces the brush border membrane vesicle uptake of glucose in streptozotocin-diabetic rats.

Glucose uptake is increased into the intestine of diabetic rats, and this adaptation can be modified further by manipulation of the type of fatty acids in the triglycerides in the diet. Jejunal brush border membrane vesicles were used to examine the uptake of D-glucose into the jejunum of non-diabetic control and streptozotocin-diabetic rats fed for two weeks in isocaloric semisynthetic diet enriched with saturated fat (beef tallow) or polyunsaturated omega-3 fatty acids (fish oil). The time-course of uptake of 100 microM glucose demonstrated an overshoot which peaked at approximately 30 seconds and declined thereafter to an equilibrium plateau. In concentration studies, glucose uptake was greater into brush border membrane vesicles of diabetic as compared with control rats. The maximal transport rate (Vmax) was increased approximately 9-fold in diabetics as compared with control rats fed beef tallow (p < 0.05), and was increased approximately 6-fold in diabetic rats fed fish oil. In diabetic rats, feeding fish oil reduced the value of the Vmax by approximately 50% as compared with diabetic rats fed beef tallow. Thus, the enhanced glucose uptake into BBM vesicles of streptozotocin-diabetic rats can be partially corrected by feeding an isocaloric semisynthetic diet enriched with polyunsaturated omega-3 fish oils.

Feeding trans fatty acids to rats has no effect on the intestinal uptake of glucose, fatty acids or cholesterol.

Trans fatty acids are produced in the manufacture of margarine, and these hydrogenated fatty acids may have a deleterious effect on the reduction in fasting levels of serum cholesterol anticipated from the feeding of cis polyunsaturated fatty acids. We undertook this study in rats to test the effect of feeding trans fatty acids on the intestinal uptake of glucose, fatty acids and cholesterol. Adult female Wistar rats were fed for 2 weeks semisynthetic, isocaloric diets containing no oleic acid (18:1), cis 18:1 or trans 18:1. There was no difference between the three dietary groups in the animals' food consumption or body weight gain. Rats fed trans 18:1 had an approximately 20% decline in the total weight of the ileum as compared with controls fed no 18:1, and therefore there was also a decline in the percentage of the ileal tissue comprised of mucosa. When comparing rats fed trans 18:1 with those fed cis 18:1 or no 18:1, there was no difference in the uptake of varying concentrations of D-glucose when expressed as nmol.100 mg tissue-1.min-1 or nmol.100 mg mucosal-1.min-1 for jejunum or for ileum. Also, there was no difference in the value of the maximal transport rate (Vmax), Michaelis constant (Km), or the contribution of passive uptake of glucose assessed with L-glucose. There was no diet-associated change in the jejunal or ileal uptake of a medium-chain length fatty acid (lauric acid), a long-chain length saturated fatty acid (palmitic acid), a monounsaturated fatty acid (oleic acid), two polyunsaturated fatty acids (linoleic and linolenic acids), or cholesterol. Thus, we conclude that 2 weeks' feeding of trans fatty acid to rats has no influence on the jejunal or ileal uptake of glucose, fatty acids or cholesterol.