| Objective: To investigate the effect and possible mechanism ofOleanolic Acid (OA) improving fatty liver induced by high fructoseconsumption in rats.Methods: Adaptively breeding24SPF male SD rats (210~230g) for7days and then randomly divided them into4groups (n=6per group):(1)control group (CON), free access to water;(2) fructose control (FRU), freeaccess to10%fructose solution (w/v, preparation every day);(3) fructoseoleanolic acid5mg/kg (FOL) and (4) fructose oleanolic acid25mg/kg(FOH), in which the fructose concentration was adjusted once per3daysbased on the results during the previous3days. There was no difference inbody weight between the groups before treatments commenced. Animals inoleanolic acid-treated groups were administered oleanolic acid5or25mg/kg for10weeks, respectively. The rats in the corresponding water-andfructose-control groups received vehicle (5%Gum Arabic) alone. On day70, rats were deprived of chow, but still had free access to water (CON) orfructose solution (FRU, FOL, FOH) overnight. Blood samples were collected by retroorbital venous puncture under ether anesthesia at9:00~12:00am for determination of plasma concentrations of TC, TG,NEFA, GLU and INSULIN. Immediately, animals were weighed and killedby prompt dislocation of the neck vertebra. Livers, epididymal andperi-renal adipose tissues (e+p WAT) were collected and weighed,respectively. The ratios of liver weight and e+p WAT weight to body weightwere calculated. Segments of liver were snap frozen in liquid nitrogen andstored at-80°C for subsequent determination of gene/protein expressionand triglyceride contents.Results:1. Compared to CON, intake of10%fructose solution decreasedintake of chow, but the total energy intake was increased (P<0.05);2. Although fructose feeding did not affect body weight, but the liverweight, e+p WAT weight and the ratio of liver weight, e+p WAT weight tobody weight were increased (P<0.05). After fructose intake was uniform infructose control and oleanolic acid-treated groups treatment with oleanolicacid did not show significant effect body weight, liver weight, e+p WATweight and the ratio of e+p WAT weight to body weight3. Under the status of feeding fructose solution, plasma concentrationsof TC, TG, GLU and INSULIN were elevated (P<0.05), whereas plasmaNEFA concentration was lower, compared to those of water feeding group.Oleanolic acid treatment at5and25mg/kg decreased plasma glucose concentration (P<0.05). However, the differences in plasma concentrationsof TC, TG, GLU and INSULIN between fructose control and oleanolicacid-treated groups were without statistic significance.4. Although fructose feeding did not significantly affect hepatic TCcontent, it increased TG content (P<0.05). In accord with this finding,increased vacuolization and Oil Red O staining area were evident onhistological examination of liver sections from fructose-fed rats comparedwith water-control rats, indicative of excess lipid droplet accumulation.Oleanolic acid treatment at25mg/kg decreased hepatic triglyceride content(P<0.05). Consistently, vacuolization and Oil Red O staining area in liverwere also reduced.5. By Real-Time PCR fructose feeding substantially increased mRNAlevels of SREBP-1c, ChREBP, FAS, ACC-1, SCD-1(P<0.05). Afteroleanolic acid treatment (25mg/kg) pronounced suppression of mRNAsencoding SREBP-1c, ChREBP, FAS, ACC-1, SCD-1was noted (P<0.05).6. The increase in nuclear SREBP-1c and ChREBP protein contentwas demonstrated by Western blot analysis (P<0.05). While the rats’protein expression levels of SREBP-1c have reduced due to high-dosed OA(P<0.05), nuclear ChREBP protein content was not significantly altered(P>0.05).Conclusion:1. High-fructose drinking induces lipid metabolic disorder and fatty liver in rats;2. OA improves fructose-induced fatty liver in rats;3. OA improves the situations of fructose-caused fatty livers by lowerthe expressions of transcription factors of liver lipid synthesis geneSREBP-1c. |
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