Lymphatic Absorption Of Cholesterol Research Articles

흰쥐에서 아로니아 추출물이 콜레스테롤과 지질의 소장흡수에 미치는 영향

본 연구는 폴리페놀 성분이 풍부한 아로니아 추출물이 실험동물의 소장에서 콜레스테롤과 지방산의 소화, 흡수에 어떤 영향을 미치는지 알아보기 위해 설계하였다. 먼저 in vivo 실험에 사용한 아로니아 추출물의 항산화 활성을 분석하기 위해 총 페놀성 화합물과 DPPH 라디칼 소거능을 측정하였다. 아로니아의 총 페놀 함량은 169.79 mg GAE/L이며, DPPH 라디칼 소거능은 23.7%로 나타났다. 다음으로 십이지장 주입관과 림프채취관을 삽입하는 미세수술인 림프관 우회수술을 진행하였다. 실험동물의 십이지장으로 연결되는 관으로 33.3 kBq SUP14/SUPC-콜레스테롤, 20.0 μmol 콜레스테롤, 396.0 μmol Na-taurocholate, 451.8 μmol triolein, 3.1 μmol α-tocopherol, 75.4 μmol retinol, PBS buffer(pH 6.4)가 포함된 지질유화액을 공급한 대조군과 추가로 아로니아 추출물을 혼합한 아로니아군으로 나누어 시간당 3 mL씩 총 8시간 동안 유화액을 주입하였다. 림프는 시간마다 채취하였고 림프로 흡수된 SUP14/SUPC-콜레스테롤, 올레산 및 총 지방산의 양을 분석하였다. 총 8시간 동안 분비된 림프액의 양은 그룹 간에 유의적인 차이가 없었다. 하지만 8시간 동안 소장으로 흡수된 14C-콜레스테롤은 대조군 39.20±2.87%, 아로니아군 34.53±3.03%로 나타나 아로니아 추출물의 공급으로 콜레스테롤의 흡수가 유의적으로 억제되는 것으로 나타났다. 지방산 중 올레산의 총 분비량은 대조군 864.36±65.27 μmol과 아로니아군 820.12±72.88 μmol이고, 총 지방산의 흡수량은 대조군 1,071.43±68.28 μmol과 아로니아군 1,015.64±78.85 μmol로 나타났다. 아로니아 추출물의 공급이 소장으로 흡수되는 올레산과 총 지방산의 양을 유의적인 수준으로 억제시키지는 못했지만, 소장 흡수를 억제시키는 경향은 보이는 것으로 나타났다. 이상의 결과들은 폴리페놀 성분이 풍부한 아로니아 추출물이 콜레스테롤의 소장흡수를 억제할 수 있다는 사실을 증명한다. 이번 연구를 바탕으로 콜레스테롤을 비롯한 여러 지질의 소화흡수를 유의적으로 억제시킬 수 있는 수준의 아로니아 섭취량을 설정하고, 아로니아의 섭취가 지질의 소장흡수를 농도 비례적으로 억제할 수 있을지를 확인하는 것이 앞으로의 과제라고 할 수 있겠다.

흰쥐 모델에서 Capsaicin이 소장 콜레스테롤 및 중성지방 흡수율에 미치는 영향

Capsaicin has been shown to affect lipid metabolism. However, it is currently not known whether capsaicin would lower the intestinal absorption of cholesterol. Thus, this study was conducted to investigate the effect of intraduodenally infused capsaicin on the lymphatic absorption of cholesterol and lipids in rats. Male Sprague-Dawley rats weighing 300~350 g were starved for 16 hr and the mesenteric lymph duct was cannulated. Each rat was infused at 3.0 mL/hr for 8 hr via the duodenal catheter with a lipid emulsion, which contained 33.3 kBq ( 14 C)-cholesterol, 20.7 μmol cholesterol, 452 μmol triolein, 3.1 μmol α-tocopherol, and 396.0 μmol Na-taurocholate without (control) or with 5.0 mg capsaicin in 24 mL PBS buffer (pH 6.4). Simultaneously, lymph was collected hourly for 8 hr. There was no significant difference in lymph flow between the groups. However, the lymphatic absorption of 14 C-cholesterol for 8 hr was significantly lower in rats infused with capsaicin than in those infused with no capsaicin. Also, the output of oleic acid for 8 hr was significantly decreased by capsaicin. However, the intestinal absorption of α-tocopherol did not differ between the groups. The results indicate that the luminal infusion of capsaicin inhibits the intestinal absorption of cholesterol and lipids in rats.

Campest-5-en-3-one, an oxidized derivative of campesterol, activates PPARα, promotes energy consumption and reduces visceral fat deposition in rats

Dietary campest-5-en-3-one (campestenone), an oxidized derivative of campesterol, significantly reduced visceral fat weight and the concentration of triacylglycerol in serum and liver of rats. Dietary campestenone dramatically increased the activities and the mRNA expressions of mitochondrial and peroxisomal enzymes involved in β-oxidation in the liver. Campestenone activated human peroxisome proliferator-activated receptor (PPAR) α as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. In contrast, dietary campestenone reduced the activities and the mRNA expressions of enzymes involved in fatty acid synthesis, except for the malic enzyme. Dietary campestenone decreased the sterol regulatory element binding protein-1 (SREBP-1) mRNA level. Energy expenditure was significantly higher in the feeding of campestenone in rats. Dietary campestenone reduced hepatic cholesterol concentration and increased fecal excretion of neutral steroids originated from cholesterol. Lymphatic absorption of cholesterol was reduced by the coadministration of campestenone in rats cannulated in the thoracic duct. These observations suggest a possibility that campestenone has an ability to prevent coronary heart disease by improving obesity and abnormality of lipid metabolism.

Phytosterol Oxidation Products Are Absorbed in the Intestinal Lymphatics in Rats but Do Not Accelerate Atherosclerosis in Apolipoprotein E–Deficient Mice

Phytosterol oxidation products (oxyphytosterols) are formed during the processing and storage of foods. However, it is unknown whether oxyphytosterols affect human health. To address these issues, we prepared beta-sitosterol and campesterol oxides, evaluated their lymphatic absorption in rats, and examined the effect of an oxyphytosterol diet on atherosclerosis in apolipoprotein (apo) E-deficient mice. The lymphatic absorption of cholesterol and 6 oxyphytosterols (7alpha-hydroxy, 7beta-hydroxy, beta-epoxy, alpha-epoxy, dihydroxy, and 7-keto) of beta-sitosterol or campesterol was assessed in thoracic duct-cannulated rats fed an AIN-93G-based diet containing 2.5 g of cholesterol, oxyphytosterols, or intact phytosterols per kg. Lymphatic recoveries (on a mass basis) of oxycampesterols (15.9 +/- 2.8%, n = 10) and oxysitosterols (9.12 +/- 1.77%, n = 10) were higher than for campesterol (5.47 +/- 1.02%, n = 12, P < 0.05) and beta-sitosterol (2.16 +/- 0.37%, n = 12, P < 0.05), but lower than for cholesterol (37.3 +/- 8.3%, n = 6, P < 0.05). Apo E-deficient mice were fed an AIN-93G-based diet containing 0.2 g oxyphytosterols or intact phytosterols per kg for 9 wk. Diet-derived oxyphytosterols accumulated in the serum, liver, and aorta. Furthermore, the oxyphytosterol diet increased oxycholesterol in the serum compared to the phytosterol diet. However, there was no significant difference between the 2 groups in the serum and aortic cholesterol concentration, the lesion area in the aortic root, or 8-iso-prostaglandin F2alpha concentration in the urine. These results indicate that exogenous oxyphytosterols are well-absorbed and accumulate in the body, but do not promote the development of atherosclerosis in apo E-deficient mice.

Effect of copper deficiency on the lymphatic absorption of cholesterol, plasma chylomicron clearance, and postheparin lipase activities.

The lymphatic absorption of cholesterol and plasma clearance of chylomicrons were investigated in Cu-deficient rats (CuD) fed 0.5 mg Cu/kg diet, as compared with Cu-adequate control rats (CuA) fed 7.5 mg/kg diet. Cholesterol absorption was measured by the 14C-radioactivity appearing in the mesenteric lymph at hourly intervals for 8 hr after an intraduodenal dose of [14C]cholesterol. The plasma clearance of chylomicrons was measured at 3, 6, and 10 min after an intravenous dose of chylomicrons labeled in vivo with [3H]retinyl ester. Cumulative [14C]cholesterol absorption and total lymphatic output of cholesterol were significantly decreased in CuD at 4 hr and thereafter, with no change in percentage distribution of free and esterified cholesterol. Over an 8-hr period, 7.3% of the dose was absorbed by CuD and 9.2% by CuA. When [3H]chylomicrons, obtained from a CuD or CuA donor rat, were injected into CuD and CuA recipient rats, the label was cleared faster in CuD during the first 3 min. At 6 and 10 min, however, no significant difference in percentage clearance of the dose was observed between the groups. The half-life (t1/2) of [3H]chylomicrons and the total 3H-radioactivity taken up by the liver during the entire 10-min period did not differ between the groups, regardless of the source of chylomicrons. The activities of both endothelial lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma were markedly lower in CuD. As expressed in micromoles fatty acid released/hr/ml plasma, the activities of LPL in CuD and CuA were 32.6 +/- 1.9 and 45.6 +/- 1.3, respectively. A similar magnitude of difference was also observed in HL activity. The data provide evidence that copper deficiency impairs the intestinal transport of cholesterol and the peripheral lipolysis of chylomicrons. The data, however, strongly suggest that the hepatic uptake of chylomicron remnants via the apo-E-dependent mechanism may not be impaired in Cu deficiency.

Effects of four taurine-conjugated bile acids on mucosal uptake and lymphatic absorption of cholesterol in the rat.

The importance of the bile acid structure on mucosal uptake and lymphatic absorption of cholesterol was investigated using four different taurine-conjugated bile acids. Pure synthetic conjugates of a trihydroxy bile acid, taurocholate, and three dihydroxy bile acids, tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate were used to completely solubilize [14C]cholesterol and polar lipids for steady rate intraduodenal infusion for 8 hr in bile fistula rats. Lymph output and esterification of [14C]cholesterol and endogenous cholesterol were measured in hourly samples. A second group of bile fistula rats was given the same bile acids as the first group but without added cholesterol or other lipid, i.e., fasting lymph fistula group. Mucosal uptake of [14C]cholesterol was studied using recovery of [14C]cholesterol from lumen and mucosa after 1-hr infusions in conscious bile fistula rats. Lymph output of [14C]cholesterol was promoted more rapidly with taurocholate than with the dihydroxy conjugates and [14C]cholesterol output differed for the three groups given dihydroxy bile acids. The mass of cholesterol in lymph, measured chemically, varied in parallel with [14C]cholesterol absorption. For fasting lymph, infusion of dihydroxy bile acids failed to produce a significant change in endogenous cholesterol output when compared with rats given saline only. Taurocholate infusion markedly increased endogenous cholesterol in lymph of fasted rats. Under all conditions where cholesterol output was stimulated, the increase could be accounted for mainly as esterified cholesterol. Mucosal uptake of [14C]cholesterol during 1-hr infusions in conscious bile fistula rats was slower with the dihydroxy bile acids than with taurocholate. The results indicate the marked effect of the number and configuration of the hydroxyl groups on the solubilizing bile acid for cholesterol absorption.

Dietary fiber and lymphatic absorption of cholesterol in the rat1–2

The indirect effects of short-term (3-day) feeding of several types of dietary fiber and nonnutritive materials on the subsequent absorption of cholesterol has been investigated in thoracic duct cannulated rats. Absorption was studied at timed intervals over 24 hr after duodenal introduction of a tracer dose of cholesterol at least 20 hr after the last feeding. In animals fed for 3 days with diets containing cholestryamine, bran, or cellulose, cholesterol absorption was significantly less than in control animals maintained on rat chow. Rats fed for 3 days with an alfalfa-containing diet showed large variations in cholesterol absorption that were not significantly different from controls. However, after 5 weeks, rats on the alfalfa diet showed a marked reduction in lymphatic absorption of the tracer sterol. These indirect effects of cholestryamine and fibers on cholesterol absorption were not attributable to a common mechanism; i.e., differences in transit times that were not significant, or direct binding of bile acids and cholesterol by the test materials.

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.