Lipid Metabolism In Hyperlipidemic Rats Research Articles

245-LB: Glucagon Infusion into the Mediobasal Hypothalamus Lowers Hepatic Triglyceride Secretion

Diabetes and obesity are associated with dysregulated liver lipid metabolism. Glucagon has an essential role in lipid metabolism, in addition to regulating glucose homeostasis. The brain is a key coordinator of whole-body metabolism. Glucagon signalling in the mediobasal hypothalamus (MBH), a forebrain region that senses hormones and nutrients to regulate metabolism, lowers hepatic glucose production and appetite. However, whether glucagon action in the MBH affects lipid homeostasis in healthy and high-fat diet (HFD)-fed animals remains unknown. We assessed glucagon signaling in the MBH in regulating hepatic TG secretion in chow-fed normolipidemic and HFD-induced hyperlipidemic rats. Stereotaxic MBH cannulation and vascular catheterizations in Sprague-Dawley rats allowed for direct MBH infusions, intravenous (IV) injections, and blood sampling. Plasma TGs were measured in 10h-fasted rats after IV poloxamer injection with concurrent MBH infusions. MBH glucagon decreased TG secretion compared to MBH vehicle control animals. This hypothalamic effect of glucagon was blocked by a simultaneous MBH co-infusion of an antagonist to the glucagon receptor (GCGR) and by protein kinase A (PKA) inhibition in the MBH in chow-fed rats. Direct MBH infusion of a PKA activator recapitulated the TG-lowering effects of MBH glucagon. Together, this suggests that MBH glucagon signals via a MBH GCGR-PKA pathway. Interestingly, both MBH glucagon and MBH PKA activation lowered TG secretion and plasma FFAs in HFD-induced hyperlipidemic animals. However, MBH glucagon did not affect hepatic TG content or liver lipogenic protein levels of MTP, FAS, or pACC:ACC of RC and HFD rats compared to their MBH vehicle controls. We demonstrate that hypothalamic glucagon modulates hepatic TG secretion via a MBH GCGR-PKA signalling pathway, and activating MBH glucagon signalling improves lipid metabolism in hyperlipidemic rats. These findings may provide therapeutic insight on lowering lipids in hyperlipidemia. Disclosure M. S. Grewal: None. B. Vasilev: None. C. M. Soltys: None. B. Lum: None. J. T. Yue: None. Funding Canadian Institutes of Health Research (PJT-378765); Canada Foundation for Innovation (37267); Canada Research Chairs Tier 2 in Brain Regulation of Metabolism

The protective effects of Levilactobacillus brevis FZU0713 on lipid metabolism and intestinal microbiota in hyperlipidemic rats

Levilactobacillus brevis FZU0713, a potential probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effects on improving lipid metabolism. This study aimed to evaluate the in vivo protective effects and possible mechanism of L. brevis FZU0713 on the disturbance of lipid metabolism in hyperlipidemic rats fed a high-fat diet (HFD). Results showed that oral administration of L. brevis FZU0713 could significantly inhibit obesity, ameliorate the lipid metabolism disorder, including serum/liver biochemical parameters and hepatic oxidative stress in HFD-fed rats. Histopathological result also indicated that dietary intervention of L. brevis FZU0713 could reduce the accumulation of lipid droplets in liver induced by 8 weeks HFD feeding. Furthermore, L. brevis FZU0713 intervention significantly increased the fecal levels of short-chain fatty acids (SCFAs, including acetate, propionate, butyrate, isobutyrate, valerate and isovalerate) in HFD-fed rats, which may be closely related to the changes of intestinal microbial composition and metabolic function. Intestinal microbiota profiling by 16S rRNA gene sequencing revealed that L. brevis FZU0713 intervention significantly altered the relative abundance of Coprococcus, Butyricicoccus, Intestinimonas, Lachnospiraceae FCS020 group, Ruminococcaceae_NK4A214 group, Ruminococcaceae_UCG-005 and UCG-014 at genus levels. Based on Spearman's rank correlation coefficient, serum and liver lipid metabolism related biochemical parameters were positively correlated with genera Ruminococcus, Pediococcus and Lachnospiraceae, but negatively correlated with genera Pseudoflavonifractor, Butyricicoccus and Intestinimonas. Furthermore, liver metabolomics analysis demonstrated that L. brevis FZU0713 had a significant regulatory effect on the composition of liver metabolites in hyperlipidemic rats, especially the levels of some important biomarkers involved in the metabolic pathways of arachidonic acid metabolism, primary bile acid biosynthesis, amino sugar and nucleotide sugar metabolism, taurine and hypotaurine metabolism, biosynthesis of unsaturated fatty acid, fructose and mannose metabolism, tyrosine metabolism, etc. Additionally, oral administration of L. brevis FZU0713 significantly regulated the mRNA levels of liver genes (including Acat2, Acox1, Hmgcr, Cd36, Srebp-1c and Cyp7a1) involved in lipid metabolism and bile acid homeostasis. In conclusion, our findings provide the evidence that L. brevis FZU0713 has the potential to improve disturbance of lipid metabolism by regulating intestinal microflora and liver metabonomic profile. Therefore, L. brevis FZU0713 may be used as a potential probiotic strain to produce functional food to prevent hyperlipidemia.

Combining lipidomics and efficacy-oriented compatibility revealed that Qi Ge decoction compatibility improved lipid metabolism in hyperlipidemic rats.

The mechanism underlying traditional Chinese medicine (TCM) compatibility is difficult to understand. This study combined lipidomics and efficacy-oriented compatibility to explore underlying compatibility mechanisms of Qi Ge decoction (QG) for improving lipid metabolism in hyperlipidemic rats. The QG was divided into three groups according to the efficacy group strategy: the Huangqi-Gegen (HG), Chenpi (CP), and QG groups. Hyperlipidemic rats were treated with QG, HG, CP, or atorvastatin for 3 weeks. The mass spectral data of widely targeted lipidomics were used to evaluate lipid changes. Principal component analysis and orthogonal partial least squares discriminant analysis were used to assess the lipidomic differences between the groups. MetaboAnalyst 5.0 was used to explore metabolic pathways. Compared with the model group, serum cholesterol, triglyceride, and hepatic steatosis were significantly reduced by QG, whereas HG and CP had no significant effects on these indexes. Lipidomics showed that QG, HG, and CP back-regulated 60, 11, and 14 lipids, respectively. Compared with HG and CP, QG had more metabolic targets in diglycerides, triglycerides, ceramides, and phosphatidylethanolamines. Pathway analysis indicated that QG mainly regulated glycerophospholipid and glycerolipid metabolism. This study provided a new method of combining lipidomics and efficacy-oriented compatibility for exploring the scientific connotation of TCM compatibility.

Hypolipidemic properties of Chlorella pyrenoidosa organic acids via AMPK/HMGCR/SREBP-1c pathway in vivo.

The aim of this study was to explore the effects and mechanisms of 95% ethanol extract of Chlorella pyrenoidosa (CPE95) on lipid metabolism in hyperlipidemic rats. For the sake of chemical composition analysis of CPE95, liquid chromatography–mass spectrometry (LC‐MS) was used for determination. After treatment with CPE95, serum high‐density lipoprotein cholesterol content of the hyperlipidemic rats was increased, while the contents of cholesterol, triglyceride, and low‐density lipoprotein cholesterol were decreased strikingly. Moreover, the result of histopathology analysis showed that the accumulation and fatty deformation of the livers were relieved. Real‐time quantitative PCR and Western blotting were used to determine the expression levels of lipid metabolism‐related genes. The gene expression level of adenosine 5’‐monophosphate‐activated protein kinase was descended, and expressions of sterol regulatory element‐binding protein‐1c, acetyl‐CoA carboxylase, and 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase were all downregulated in the CPE95‐treated rats. It suggested that CPE95 may effectively improve the hyperlipidemia in rats and would be potential for functional food component to reduce blood lipid.

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet.

The objective of this study was to investigate the effects of simvastatin (SIM) on lipid metabolism disorders and gut microbiota in high-fat diet-induced hyperlipidemic rats. The obtained results revealed that feeding rats with SIM (20 mg/kg/day) significantly decreased serum lipid level and inhibited hepatic lipid accumulation and steatosis. Histological analysis further indicated that SIM reduced lipid deposition in adipocytes and hepatocytes in comparison with that of the HFD group. The underlying mechanisms of SIM administration against HFD-induced hyperlipidemia were also studied by UPLC-Q-TOF/MS-based liver metabonomics coupled with pathway analysis. Metabolic pathway enrichment analysis of liver metabolites with significant difference in abundance indicated that fatty acids metabolism and amino acid metabolism were the main metabolic pathways altered by SIM administration. Meanwhile, operational taxonomic units (OTUs) analysis revealed that oral administration of SIM altered the composition of gut microbiota, including Ruminococcaceae (OTU960) and Lactobacillus (OTU152), and so on. Furthermore, SIM treatment also regulated the mRNA levels of the genes involved in lipid and cholesterol metabolism. Immunohistochemistry (IHC) analysis of the liver-related proteins (CD36, CYP7A1 and SREBP-1C) showed that oral administration of SIM could regulate the levels of the protein expression related to hepatic lipid metabolism.

Effects of Single Probiotic- and Combined Probiotic-Fermented Milk on Lipid Metabolism in Hyperlipidemic Rats

Previous studies have shown that probiotics have positive effects on hyperlipidemia by lowering the serum lipid concentration and improving the lipid profile. To explore the mechanism by which probiotic-fermented milk improves lipid metabolism, the transcription of genes regulated by liver X receptors (LXRs), 5′-AMP-activated protein kinase, and the farnesoid X receptor (FXR), which play integral roles in lipid metabolism, was investigated in hyperlipidemic rats. Compared with rats fed a high-fat diet, the administration of probiotic-fermented milk significantly lowered the levels of total cholesterol (TC) and total triglycerides (TG) in rat serum and viscera (P < 0.05) and significantly increased the level of total bile acid in the rat liver and small intestine (P < 0.05). The quantitative PCR results showed that the probiotics ameliorated the TC levels in the rats by activating the transcription of genes involved in the LXR axis, which promoted TC reverse transport and increased the conversion of TC to bile acids. The level of TG in the hyperlipidemic rats was ameliorated by the inhibition of the transcription of carbohydrate reaction element binding protein genes and activation of the transcription of PPARα genes. The regulation of lipid metabolism-related gene transcription by the single probiotic (Lactobacillus rhamnosus LV108)-fermented milk was more effective than that by the combined probiotic (L. rhamnosus LV108, Lactobacillus casei grx12, and Lactobacillus fermentum grx08)-fermented milk (P < 0.05).

Effects of sanshoamides and capsaicinoids on plasma and liver lipid metabolism in hyperlipidemic rats.

The objective of this study was to determine the effects of sanshoamides and capsaiciniods on plasma and liver lipid levels and the mRNA expression levels of key receptors involved in cholesterol metabolism in hyperlipidemic rats. A total of 56 three-week-old female Sprague-Dawley rats were assigned to 7 treatment groups based on initial body weight (n = 8 rats per group). With certain combinations of sanshoamides and capsaicinoids significantly increased food intake, reduced lipid levels in blood and liver, improved histological characteristics of a fatty liver, down regulated mRNA expression levels of cholesterol 7-alpha-hydroxylase (CYP7A1), 3-hydroxyl-3-methylglutary CoA (HMG-CoA) and Farnesoid X Receptor (FXR) in liver and apical sodium-dependent bile acid transporter, Ileal Bile Acid Binding Protein and FXR in the ileum in hyperlipidemic rats. These results indicated that dietary supplementation with sanshoamides and capsaicinoids reduced blood lipid levels and improved cholesterol metabolism in hyperlipidemic rats.

Effects of pure total flavonoids from Citrus changshan-huyou on blood lipid metabolism in hyperlipidemic rats

To observe and investigate the effects and mechanisms of the pure total flavonoids from Citrus changshan-huyou(PTFC) on blood lipid metabolism in hyperlipidemic rats. SD rats were fed with high fat diet for 4 weeks to induce hyperlipidemic rats model, meanwhile three dosages (50, 100, 200 mg•kg ⁻¹•d ⁻¹) of PTFC were administrated intragastrically for 4 weeks respectively.After 2 weeks of modeling, their tail blood was taken and serum TC, TG, and HDL-C levels were detected by biochemical method and their body weight was measured. After 4 weeks of modeling, their body weight was measured and liver weight was measured, then the levels of TC, TG, HDL-C, LDL-C, ALT, AST, MDA and SOD in serum were detected to calculate lipid comprehensive index(LDL-C/HDL-C and LDL-C/TC ratios) and atherogenic index(AI); in addition, MDA and SOD levels were detected by biochemical method. The hitopathological changes of the liver tissues were observed by HE staining; the protein expression levels of PPAR-α, Lpl, and Lipc were detected by ELISA; and the mRNA expression levels of PPAR-α in the liver tissue were detected by Real-time PCR. The results showed that gavage administration of the PTFC significantly decreased the body weight, liver weight, liver index, serum ALT and AST activities, the levels of serum TC, TG, LDL-C, LDL-C/HDL-C, AI and increased serum HDL and LDL/TC level. Moreover, the PTFC significantly enhanced SOD activity and decreased the concentration of MDA in serum and liver tissue. Further mechanism investigation indicated that PTFC inhibited serum lipid accumulation by increasing the expressions PPAR-α, Lpl, Lipc protein and PPAR-α mRNA of the liver tissues. PTFC could actively regulate blood lipid metabolism by ameliorating hepatic function, improving the body's antioxidant capacity, lowering levels of oxidative stress, as well as positively regulating the expression levels of PPAR-α, Lpl, Lipc protein and PPAR-α mRNA of the liver tissues in rats.

Effects of extract from cole pollen on lipid metabolism in experimental hyperlipidemic rats.

In order to evaluate the effects of extract by SCE (supercritical carbon dioxide extraction) from cole pollen on lipid metabolism in hyperlipidemic rats, the experimental hyperlipidemic rats were established by providing with high fat diets, and randomized into six groups. After four weeks of perfusion diets into stomach, the rats were executed, and lipid levels of serum and hepatic tissue were detected. The serum levels of TC and TG were significantly lower in the pollen extract groups and MC group than in HFC group. Hepatic TC levels were decreased in rats fed pollen extract and lovastatin compared with HFC group. A higher concentration of HDL-C and apoAI in hepatic tissue was measured after intake of the pollen extract compared to the HFC group (P < 0.05). LCAT activity in serum of pollen extract groups was significantly higher than that in HFC group, and also HMG-CoA reductase showed decreasing tendency in pollen extract groups. The contents of DHA in pollen extract groups were found higher than those in HFC group. Cole pollen extract enriched in alpha-linolenic acid is likely to be a novel source of ALA which is probably responsible for favorable lipid changes through promoting transportation, excretion, and metabolism of cholesterol in hepatic tissue and serum.

Effect of Soymilk Fermented with Lactobacillus plantarum P-8 on Lipid Metabolism and Fecal Microbiota in Experimental Hyperlipidemic Rats

We recently identified a novel probiotic strain Lactobacillus plantarum P-8 (L. plantarum P-8), which has been characterized in detail with regard to its probiotic potential. In the present study, soymilk fermented with L. plantarum P-8 was examined for its effects on diet-induced hyperlipidemia in Wistar rats. The experimental animals were divided into four groups: control group (C group), model group (M group), soymilk group (SM group) and fermented soymilk group (FSM group). The serum lipid levels, hepatic fat deposition, serum oxidative stress parameters, hepatic marker enzymes levels, organ indices, gut bacteria and fecal fat contents were analyzed. Fermented soymilk reduced the concentration of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in serum, with a significant elevation in high-density lipoprotein cholesterol (HDL) concentration. Our results also suggested the beneficial effects of fermented soymilk on the liver function, hyperlipidemia-induced oxidative stress and intestinal bacteria. Moreover, fermented soymilk could enhance the fecal excretion of TC, TG and bile acids. These findings demonstrated that soymilk fermented with L. plantarum P-8 was effective in improving the lipid metabolism in hyperlipidemic rats. The hypolipidemic effect of fermented soymilk was partly due to the inhibition of dietary fats absorption and regulation of fecal fats excretion mediated by gut bacteria.

구운 마늘 분말이 고지방-고콜레스테롤 식이를 급여한 흰쥐의 체내 지질대사에 미치는 효과

본 연구는 구운 마늘 분말의 혈청, 간 및 지방조직의 체내 지질대사 개선효과와 항비만 효과를 살펴보기 위하여 5주령된 흰쥐 수컷 32마리를 10일간 적응시킨 후 정상군(N), 고지방-고콜레스테롤 식이군(대조군, C), 고지방-고콜레스테롤 식이와 1.5% 구운 마늘 분말 첨가군(GPL) 및 고지방-고콜레스테롤 식이와 3% 구운 마늘 분말 첨가군(GPH)으로 나누어 4주간 실시하였다. 체중증가량과 식이섭취량은 실험군들 간에 유의한 차이를 보이지 않았고, 식이효율은 고지방-고콜레스테롤을 급여한 군들(C, GPL, GPH)이 대조군(C)에 비하여 증가하였다. 체중 100 g 당 간조직 및 장간막지방조직의 무게는 구운 마늘 급여에 따른 유의차는 없었고, 부고환지방 조직의 무게는 구운 마늘 분말 1.5%와 3% 첨가군들(GPL, GPH)이 대조군(C)에 비하여 유의하게 감소하였다. 고지방-고콜레스테롤 식이로 인하여 혈청 ALT, AST, ALP 및 LDH 활성이 증가되었으나, 혈청 AST 및 LDH 활성은 3% 구운 마늘 분말 첨가로 유의하게 저하되었다. 혈청 중성지방과 총콜레스테롤 함량은 고지방-고콜레스테롤 식이 급여로 유의하게 증가하였으며, 구운 마늘 분말 첨가 수준이 증가할수록 감소하는 경향을 보였으며 특히 3% 구운 마늘 분말첨가군(GPH)은 대조군(C)에 비하여 유의하게 감소되었다. 고지방-고콜레스테롤 식이 급여로 감소되어진 혈청 HDL-콜레스테롤 함량은 구운 마늘 분말 첨가로 증가하였고, 혈청 LDL-콜레스테롤 함량, 동맥경화지수 및 심혈관위험지수는 구운 마늘 분말 첨가로 감소하여 동맥경화 및 심혈관 질환의 발병 위험률 감소 효과를 나타내었다. 고지방-고콜레스테롤 식이로 간과 지방조직의 중성지방 및 총콜레스테롤 함량이 증가되었으며, 고지방-고콜레스테롤 식이로 증가된 간조직과 장간막지방조직의 총콜레스테롤 함량, 부고환조직의 중성지방 함량은 구운 마늘 급여로 저하되었다. 이상의 실험 결과 구운 마늘은 고지방-고콜레스테롤 식이를 급여한 흰쥐의 혈청, 간 및 지방조직의 지질대사 개선에 긍정적인 영향을 미치는 것으로 나타나 체내 지질대사 개선과 심혈관계 질환 예방효과가 클 것으로 기대된다.

Mechanism study of chitosan on lipid metabolism in hyperlipidemic rats.

It has been reported that plasma and liver cholesterol concentrations decrease when animals are fed with chitosan, but the mechanism is unclear. Four wk old male SD (Sprague-Dawley) rats were fed a commercial rat diet (cholesterol-free diet, negative control, NC), cholesterol-enriched diet containing 5% of chitosan (CH) or cholesterol-enriched diet containing 5% of cellulose (CE) and 5% of lard for 12 weeks. We would investigated the effects of chitosan on plasma and liver cholesterol levels, liver weight, bile acids concentrations of fecal and hepatic LDL receptor mRNA expression. The results showed that chitosan could decrease levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) in plasma (p<0.05), and TC, total triglyceride (TG) in liver (p<0.05), and increase fecal bile acids excretion (p<0.05), but the levels of TG and HDL-C in plasma was unchanged (p>0.05). In addition, the result of RT-PCR test showed that saturated fat and cholesterol fed could significantly induce the reduction of LDL receptor mRNA levels, while chitosan could increase hepatic LDL receptor mRNA levels. This study suggested that chitosan improve lipid metabolism by regulating TC and LDL-C by upregulating of hepatic LDL receptor mRNA expression, increasing the excretion of fecal bile acids.

Effects of Cordyceps militans Cultivated on Rice on Lipid Metabolism in Rats Fed High Fat-cholesterol Diets

Dongchunghacho rice, produced by cultivating Dongchunghacho fungus on rice, could be an effective functional food because it offers added value to rice and thus increases rice consumption. However, the physiological effect of Dongchunghacho rice has not been reported yet although there is increasing consumers demand. Therefore, we investigated the effect of Dongchunghacho rice (unpolished rice cultivated with Cordyceps militaris) on lipid metabolism in hyperlipidemic rats. Forty of 8 wk-old male Sprague-Dawley rats were divided into four groups after a 1 week of adaptation period and fed either a normal diet (66% polished rice diet, NC), high fat (12 g/100 g)-high cholesterol (1 g/100 g) diet with 53% polished rice (HC), or high fat-high cholesterol diets supplemented with 30% of the total rice as either unpolished rice (UR) or Dongchunghacho rice (DR). After 4 weeks, rats fed the Dongchunghacho rice diet with high fat and cholesterol had dramatically lower plasma LDL cholesterol concentrations and atherogenic indexes and higher plasma HDL cholesterol levels compared with the rats consuming polished rice or unpolished rice with high fat and cholesterol diet. Dongchunghacho rice led to less total lipid and total cholesterol accumulation in liver. However, these significant reductions in plasma or hepatic lipid profiles were not closely correlated with fecal total lipid or total cholesterol excretion. The plasma concentration of total cholesterol and triglycerides were not affected by Dongchunghacho rice. This hypolipidemic effect of Dongchunghacho rice seemed to be unrelated to unpolished rice itself, because the plasma and hepatic lipid profiles of UR group were not different from that of the HC group. These results suggest that unpolished rice containing cultivated Cordyceps militaris can improve plasma and hepatic lipid profiles in rats fed with high fat-high cholesterol diet.

Effect of flavonoids morin; quercetin and nicotinic acid on lipid metabolism of rats experimentally fed with triton

Atherosclerosis is a coronary disease where deposition of lipids in the arteries leads to problems of blood circulation. The present work evaluates the action of the flavonoids morin, quercetin and nicotinic acid isolated in association on lipid metabolism in hyperlipidemic rats. Blood serum levels cholesterol, cholesterol-HDL, and triacylglycerids have been analysed following the intraperitoneal administration of the flavonoid compounds dissolved in propyleneglycol by in doses of 5mg/kg body weight. Quercetin presented the largest percentual reduction of cholesterol. The best results for cholesterol-HDL have been obtained with-nicotinic acid alone while morin-nicotinic acid combination showed the best triacylglycerols results. Results showed that flavonoids could be beneficious in the treatment of coronary diseases.

Effect of KRN4884 on lipid metabolism in hyperlipidemic rats

1. 1. KRN4884 is a novel pyridinecarboxamidine type potassium channel opener. 2. 2. To determine whether KRN4884 affects lipid metabolism, we investigated its effects on serum lipid levels by using two types of hyperlipidemic rats: genetically hyperlipidemic obese Zucker rats and diet-induced hyperlipidemic rats fed a high fat diet. KRN4884 dose dependently decreased systolic blood pressure in Zucker rats. 3. 3. Oral administration of KRN4884 (1–10 mg/(kg day) for 14 days dose dependently reduced serum triglyceride levels in Zucker rats. The reductions in serum triglyceride were associated with reductions in triglyceride in chylomicron and very low density lipoprotein. 4. 4. KRN4884 produced no change in serum insulin and glucose levels in Zucker rats. 5. 5. KRN4884 exhibited a similar triglyceride lowering effect in diet-induced hyperlipidemic rats. 6. 6. These results suggest that KRN4884 has a beneficial effect on serum triglyceride levels as well as a hypotensive effect.

Effects of etofibrate, clofibrate and nicotinic acid on lipid metabolism in hyperlipidemic rats

1. The hypolipidemic action of etofibrate has been studied on hypercholesterolemic, hypertriglyceridemic and hyperlipidemic rats and the results have been compared with those of treatment with two other lipid-lowering drugs, clofibrate and nicotinic acid. 2. Serum and liver cholesterol, triglyceride, phospholipid and free fatty acid levels were determined. Liver lipid biosynthesis from [1- 14C]acetate was also studied. 3. Etofibrate and clofibrate produced similar effects on serum lipids of hypercholesterolemic rats but a more potent effect of etofibrate on lowering liver cholesterol was found. Eeofibrate showed the most protective action in hypertriglyceridemic rats. Etofibrate and clofibrate were similarly effective in reducing serum cholesterol and triglyceride and liver triglyceride levels of hyperlipidemic rats.