The effect of high-fat diet and inhibition of ceramide production on insulin action in liver

Liver, as one of the most important organs involved in lipids and glucose metabolism, is perceived as a key tissue for pharmacotherapy of insulin resistance (IRes) and type 2 diabetes. Ceramides (Cer) are biologically active lipids, which accumulation is associated with the induction of muscle IRes. We sought to determine the role of intrahepatic bioactive lipids production on insulin action in liver of insulin-resistant rats and after myriocin administration. The experiments were conducted on male Wistar rats divided into three groups: Control, fed high-fat diet (HFD), and fed HFD and treated with myriocin (HFD/Myr). Before sacrifice, the animals were infused with a [U-¹³C]palmitate to calculate lipid synthesis rate by means of tracer incorporation technique in particular lipid groups. Liver Cer, diacylglycerols (DAG), acyl-carnitine concentration, and isotopic enrichment were analyzed by LC/MS/MS. Proteins involved in lipid metabolism and insulin pathway were analyzed by western blot analysis. An OGTT and ITT was also performed. HFD-induced IRes and increased both the synthesis rate and the content of DAG and Cer, which was accompanied by inhibition of an insulin pathway. Interestingly, myriocin treatment reduced synthesis rate not only of Cer but also DAG and improved insulin sensitivity. We conclude that the insulin-sensitizing action of myriocin in the liver is a result of the lack of inhibitory effect of lipids on the insulin pathway, due to the reduction of their synthesis rate. This is the first study showing how the synthesis rate of individual lipid groups in liver changes after myriocin administration.     

Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice

Methionine-S-sulfoxide reductase (MsrA) protects against high-fat diet-induced insulin resistance due to its antioxidant effects. To determine whether its counterpart, methionine-R-sulfoxide reductase (MsrB) has similar effects, we compared MsrB1 knockout and wild-type mice using a hyperinsulinemic-euglycemic clamp technique. High-fat feeding for eight weeks increased body weights, fat masses, and plasma levels of glucose, insulin, and triglycerides to similar extents in wild-type and MsrB1 knockout mice. Intraperitoneal glucose tolerance test showed no difference in blood glucose levels between the two genotypes after eight weeks on the high-fat diet. The hyperglycemic-euglycemic clamp study showed that glucose infusion rates and whole body glucose uptakes were decreased to similar extents by the high-fat diet in both wild-type and MsrB1 knockout mice. Hepatic glucose production and glucose uptake of skeletal muscle were unaffected by MsrB1 deficiency. The high-fat diet-induced oxidative stress in skeletal muscle and liver was not aggravated in MsrB1-deficient mice. Interestingly, whereas MsrB1 deficiency reduced JNK protein levels to a great extent in skeletal muscle and liver, it markedly elevated phosphorylation of JNK, suggesting the involvement of MsrB1 in JNK protein activation. However, this JNK phosphorylation based on a p-JNK/JNK level did not positively correlate with insulin resistance in MsrB1-deficient mice. Taken together, our results show that, in contrast to MsrA deficiency, MsrB1 deficiency does not increase high-fat diet-induced insulin resistance in mice.     

Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet

Oxidative stress, physical inactivity and high-fat (FAT) diets are associated with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects of physical training (PT) were evaluated in rats with MS induced by FAT diet for 13 weeks, on oxidative stress and insulin signaling in the liver, during the last 6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine aminotransferase, glucose and insulin. Livers of FAT-SED rats increased superoxide dismutase activity, thiobarbituric acid-reactive substances, protein carbonyl and oxidized glutathione (GSSG); and decreased catalase activity, reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin, total cholesterol, MAP and HR; and their livers increased superoxide dismutase and catalase activities, the reduced glutathione/GSSG ratio and the expression of peroxisome proliferator-activated receptor gamma and insulin receptor compared to FAT-SED rats. These findings indicated adaptive responses to PT by restoring the oxidative balance and insulin signaling in the liver and certain biometric and biochemical parameters as well as MAP in MS rats.     

A high-fat diet and high-fat and high-cholesterol diet may affect glucose and lipid metabolism differentially through gut microbiota in mice

This study was conducted to investigate the effects of a high-fat diet (HFD) and high-fat and high-cholesterol diet (HFHCD) on glucose and lipid metabolism and on the intestinal microbiota of the host animal. A total of 30 four-week-old female C57BL/6 mice were randomly divided into three groups (n=10) and fed with a normal diet (ND), HFD, or HFHCD for 12 weeks, respectively. The HFD significantly increased body weight and visceral adipose accumulation and partly lowered oral glucose tolerance compared with the ND and HFHCD. The HFHCD increased liver weight, liver fat infiltration, liver triglycerides, and liver total cholesterol compared with the ND and HFD. Moreover, it increased serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol compared with the ND and HFD and upregulated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase significantly. The HFHCD also significantly decreased the α-diversity of the fecal bacteria of the mice, to a greater extent than the HFD. The composition of fecal bacteria among the three groups was apparently different. Compared with the HFHCD-fed mice, the HFD-fed mice had more Oscillospira, Odoribacter, Bacteroides, and [Prevotella], but less [Ruminococcus] and Akkermansia. Cecal short-chain fatty acids were significantly decreased after the mice were fed the HFD or HFHCD for 12 weeks. Our findings indicate that an HFD and HFHCD can alter the glucose and lipid metabolism of the host animal differentially; modifications of intestinal microbiota and their metabolites may be an important underlying mechanism.     

High-fat diet reduces novelty-induced expression of activity-regulated cytoskeleton-associated protein

Chronic high-fat-diet (HFD) consumption can lead to the development of brain insulin resistance, which then exerts deleterious effects on learning and memory. Activity-regulated cytoskeleton-associated protein (Arc) is a memory-related protein, and its expression can be induced by insulin stimulation. In HFD-fed animals, their basal Arc protein levels in cerebral cortex and hippocampus are reduced. However, the effects of HFD on novelty-induced Arc protein expression that is important for cognitive function is still unknown. In the present study, after feeding HFD (60% kcal from fat) for 5 weeks, mice developed brain insulin resistance and had a significant reduction in the novelty-induced but not the basal Arc protein levels in their hippocampi. Further experiments were performed in primary rat hippocampal neurons. The results show that, under the condition of neuronal insulin resistance, acute insulin stimulation induced less activation of the phosphatidylinositol 3-kinase/protein kinase B/p70 ribosomal S6 kinase (PI3K/Akt/p70S6K) pathway, resulting in reduced induction of Arc protein expression. Accordingly, it is suggested that following HFD feeding, the reduction in novelty-induced Arc protein expression in animal's hippocampus is probably related to a suppressed activation of the PI3K/Akt/p70S6K pathway due to the existence of brain insulin resistance.     

Histopathological changes in rat pancreas and skeletal muscle associated with high fat diet induced insulin resistance

The effects of a high fat diet on the development of diabetes mellitus, insulin resistance and secretion have been widely investigated. We investigated the effects of a high fat diet on the pancreas and skeletal muscle of normal rats to explore diet-induced insulin resistance mechanisms. Forty-four male Wistar rats were divided into six groups: a control group fed standard chow, a group fed a 45% fat diet and a group fed a 60% fat diet for 3 weeks to measure acute effects; an additional three groups were fed the same diet regimens for 8 weeks to measure chronic effects. The morphological effects of the two high fat diets were examined by light microscopy. Insulin in pancreatic islets was detected using immunohistochemistry. The homeostasis model assessment of insulin resistance index and insulin staining intensity in islets increased significantly with acute administration of high fat diets, whereas staining intensity decreased with chronic administration of the 45% fat diet. Islet areas increased significantly with chronic administration. High fat diet administration led to islet degeneration, interlobular adipocyte accumulation and vacuolization in the pancreatic tissue, as well as degeneration and lipid droplet accumulation in the skeletal muscle tissue. Vacuolization in the pancreas and lipid droplets in skeletal muscle tissue increased significantly with chronic high fat diet administration. We suggest that the glucolipotoxic effects of high fat diet administration depend on the ratio of saturated to unsaturated fatty acid content in the diet and to the total fat content of the diet.     

Pollen Typhae total flavone improves insulin resistance in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats

Pollen Typhae total flavone (PTF), the extract from Pollen Typhae, is reported to enhance glucose uptake in C2C12 myotubes in vitro, but the convincing evidence is lacking in vivo. In this study, PTF ameliorated insulin resistance and dyslipidemia, but failed to significantly increase body weight in type 2 diabetic rats induced by high-fat diet and low-dose streptozotocin.     

Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

A high-fat diet is known to induce atherosclerosis in animal models. Dietary factors and timing of atherogenic food delivery may affect plasma lipoprotein content composition and its potential atherogenic effect. Increasingly often, humans spend periods/days eating in a completely unregulated way, ingesting excessive amounts of food rich in oils and fats, alternating with periods/days when food intake is more or less correct. We investigate the effect on lipid homeostasis of a high-fat diet administered either continuously or intermittently. We investigated control pigs receiving standard diet (C, n=7), pigs receiving a high-fat diet every day for 10 weeks (CHF, n=5), and pigs receiving a high-fat diet every other week for 10 weeks (IHF, n=7). IHF animals were shown to have a different lipid profile compared with CHF animals, with a significant increase in high-density lipoproteins (HDL) levels with respect to C and CHF groups. CHF also showed significantly higher values of TC/HDL cholesterol compared with C and IHF. Hepatic expression analysis of genes involved in lipid homeostasis showed an increasing trend of nuclear receptor LXRα along with its target genes in the CHF group and in the IHF group, whereas SREBP2 and LDLr were significantly inhibited. A significant correlation was found between ABCA1 expression and circulating levels of HDL-C. Periodic withdrawals of a high-fat atherogenic diet compared with a regular administration results in a different adaptive response of lipoprotein metabolism, which leads to a significantly higher plasma level of HDL-C and lower TC/HDL-C.     

Isocaloric intake of a high‐fat diet promotes insulin resistance and inflammation in Wistar rats

The aim of this study was to investigate the effect of isocaloric intake from a high‐fat diet (HFD) on insulin resistance and inflammation in rats. Male Wistar rats were fed on an HFD (n = 12) or control diet (n = 12) for 12 weeks. Subsequently, all animals were euthanized, and blood glucose, insulin, free fatty acids, C‐reactive protein, lipid profile, cytokines and hepatic‐enzyme activity were determined. Carcass chemical composition was also analyzed. During the first and the twelfth weeks of the experimental protocol, the oral glucose tolerance test and insulin tolerance test were performed and demonstrated insulin resistance (P < 0.05) in the HFD group. Although food intake (g) was lower (P < 0.05) in the HFD group compared with the control group, the concentration of total cholesterol, low‐density lipoprotein, C‐reactive protein and liver weight were all significantly higher. The kinase inhibitor of κB, c‐Jun N‐terminal kinase and protein kinase B expressions were determined in the liver and skeletal muscle. After an insulin stimulus, the HFD group demonstrated decreased (P = 0.05) hepatic protein kinase B expression, whereas the kinase inhibitor of κB phospho/total ratio was elevated in the HFD muscle (P = 0.02). In conclusion, the isocaloric intake from the HFD induced insulin resistance, associated with impaired insulin signalling in the liver and an inflammatory response in the muscle. Copyright © 2012 John Wiley & Sons, Ltd.     

Maternal obesogenic diet combined with postnatal exposure to high-fat diet induces metabolic alterations in offspring

Maternal obesity has been shown to impact the offspring health during childhood and adult life. This study aimed to evaluate whether maternal obesity combined with postnatal exposure to an obesogenic diet could induce metabolic alterations in offspring. Female CD1 mice were fed a control diet (CD, 11.1% of energy from fat) or with a high-fat diet (HFD, 44.3% of energy from fat) for 3 months. After weaning, pups born from control and obese mothers were fed with CD or HFD for 3 months. Both mothers and offspring were weighted weekly and several blood metabolic parameters levels were evaluated. Here, we present evidence that the offspring from mothers exposed to a HFD showed increased acetylation levels of histone 3 on lysine 9 (H3K9) in the liver at postnatal Day 1, whereas the levels of acetylation of H4K16, dimethylation of H3K27, and trimethylation of H3K9 showed no change. We also observed a higher perinatal weight and increased blood cholesterol levels when compared to the offspring on postnatal Day 1 born from CD-fed mothers. When mice born from obese mothers were fed with HFD, we observed that they gained more weight, presented higher blood cholesterol levels, and abdominal adipose tissue than mice born to the same mothers but fed with CD. Collectively, our results point toward maternal obesity and HFD consumption as a risk factor for epigenetic changes in the liver of the offspring, higher perinatal weight, increased weight gain, and altered blood cholesterol levels.     

An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila

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Effect of aerobic exercise training on non-alcoholic fatty liver disease induced by a high fat diet in C57BL/6 mice

[Purpose]

The aim of this study was to investigate the effects of aerobic exercise training on a high fat diet (HFD)-induced fatty liver and its metabolic complications in C57BL/6 mice.

[Methods]

Mice at 5-month old (n = 30) were randomly assigned to standard chow (SC + CON, n = 10) and high-fat diet (HFD, n = 20), and they were subjected to SC and HFD, respectively, for 23-week. After 15-week of HFD, mice in the HFD group were further assigned to HFD (HFD + CON, n = 10) or exercise training (HFD + EX, n = 10) groups. The HFD + EX mice were subjected to aerobic treadmill running during the last 8-week of the 23-week HFD course. Outcomes included hepatic steatosis, insulin resistance, and expression of genes involved in mitochondrial function and/or fatty oxidation as well as de novo lipogenesis and/or triacylglycerol (TAG) synthesis.

[Results]

Treadmill running ameliorated impaired glucose tolerance and insulin resistance secondary to the HFD. The beneficial effects of treadmill running were associated with enhanced molecular markers of mitochondrial function and/or fatty acids oxidation (i.e., PPARα and CPT1a mRNAs, pAMPK/AMPK, pACC, and SIRT1 protein) as well as suppressed expression of de novo lipogenesis and/or TAG synthesis (i.e., SREBP1c, lipin1 and FAS mRNAs) in the liver.

[Conclusion]

The current findings suggest that aerobic exercise training is an effective and non-pharmacological means to combat fatty liver and its metabolic complications in HFD-induced obese mice.     

Combined effect of high-fat diet and copper deficiency during gestation on fetal copper status in the rat

We have previously shown that a low-copper (Cu) diet produced alterations in placental Cu transport and fetal Cu stores. Because Cu deficiency has been associated with lipid deposition in rat dam liver, we hypothesized that a high fat intake, a prevalent dietary habit in many populations, may worsen fetal Cu status and its closely linked iron (Fe) deposits. Pregnant rats were fed one of four diets during the second half of gestation: NFNCu: normal fat (7%), normal Cu (6 mg/kg); HFNCu: high fat (21%), normal Cu; NFLCu: normal fat, low Cu (0.6 mg/kg), and HFLCu: high fat, low Cu. One day before delivery, dams were anesthetized, and maternal as well as fetal plasma and tissues were obtained. Maternal, fetal, and placental weights were indistinguishable regardless of the group. Dam plasma Cu and placental Cu were lower in both LCu groups than in the NFNCu or the HFNCu groups. However, fetal plasma Cu was similar in all treatment groups. Dam and fetal liver Cu stores were reduced in the LCu groups compared to the NCu groups. This resulted in lower fetal/maternal liver Cu ratios in the NFLCu (1.79 ± 0.14,p < 0.05) and HFLCu (1.59 ± 0.21,p < 0.05) as compared to the NFNCu (4.12 ± 0.44) and the HFNCu (4.15 ± 0.27). Dam liver Fe was higher in the NFNCu than in HFNCu group (1.10 ± 0.8 vs. 0.89 ± 0.06 μmol/g,p < 0.05); fetal liver Fe from HFNCu and NFLCu dams was lower than that from NFNCu fetuses (NFNCu: 2.42 ± 0.14; HFNCu: 1.92 ± 0.15,p < 0.05; NFLCu: 1.81 ± 0.10,p < 0.01). Fetuses of the HFLCu group had a lower heart Fe than the NFNCu group (0.56 ± 0.03 vs. 44.0 ± 3.0 μg/g,p < 0.01). These data indicate that a maternal high-fat diet can potentially aggravate the effects of Cu deficiency by further altering fetal Cu and Fe tissue stores.     

Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin in non-obese rats

Objective: We assessed the relationship between a high‐fat (HF) diet and central apnea during rapid eye movement and non‐rapid eye movement sleep stages by recording ventilatory parameters in 28 non‐obese rats in which insulin resistance had been induced by an HF diet. We also studied whether metformin (an anti‐hyperglycemic drug frequently used to treat insulin resistance) could reverse sleep apnea or prevent its occurrence in this experimental paradigm. Research Methods and Procedures: Rats were fed with a standard diet (10 rats), an HF diet (8 rats), or an HF diet concomitantly with metformin treatment (10 rats). Each animal was instrumented for electroencephalographic and electromyographic recording. After 3 weeks, ventilatory parameters during sleep were recorded with a body plethysmograph. All rats were treated with metformin for 1 week, after which time the ventilatory measurements were measured again. Results: Our results showed that the three groups of animals did not differ in terms of body growth over the entire experimental period. The HF diet did not modify sleep structure or minute ventilation in the different sleep stages. A great increase (+266 ± 48%) in central apnea frequency was observed in insulin‐resistant rats. This was explained by an increase in both post‐sigh (+195 ± 35%) and spontaneous apnea (+437 ± 65%) in the different sleep stages. These increases were suppressed by metformin treatment. Discussion: Insulin resistance induced by the HF diet could be the promoter of sleep apnea in non‐obese rats. Metformin is an efficient curative and preventive treatment for sleep apnea, suggesting that insulin resistance modifies the ventilatory drive independently of obesity.     

表没食子儿茶素没食子酸酯抑制肥胖大鼠肝中TLR4炎症通路及胰岛素抵抗

目的探讨表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)对肥胖大鼠肝组织中Toll样受体4(Toll-like receptor 4,TLR4)炎症通路以及胰岛素抵抗的影响。方法将30只雄性SD大鼠随机分为普食组(NC)和高脂饮食组(HFD)。喂养16周后,将高脂饮食组随机分为HFD组与EGCG组继续喂养16周,检测相关代谢指标,测定肝组织甘油三酯含量,并进行油红染色评估肝脂质聚集情况;实时荧光定量PCR检测其肝脏中TLR4和TNF受体相关因子6(TNF receptor associated factor 6,TRAF6)mRNA水平;蛋白质印记检测其肝组织中TLR4信号通路及胰岛素信号通路相关蛋白水平。结果EGCG明显降低大鼠肝脏甘油三酯浓度及脂质聚集、TLR4和TRAF6 mRNA水平,TLR4信号通路相关蛋白水平及胰岛素信号通路相关蛋白水平。结论EGCG抑制肥胖大鼠肝组织中TLR4通路以及胰岛素抵抗。     

A high-fat diet catalyzes progression to hyperglycemia in mice with selective impairment of insulin action in Glut4-expressing tissues

Insulin resistance impairs postprandial glucose uptake through glucose transporter type 4 (GLUT4) and is the primary defect preceding type 2 diabetes. We previously generated an insulin-resistant mouse model with human GLUT4 promoter-driven insulin receptor knockout (GIRKO) in the muscle, adipose, and neuronal subpopulations. However, the rate of diabetes in GIRKO mice remained low prior to 6 months of age on normal chow diet (NCD), suggesting that additional factors/mechanisms are responsible for adverse metabolic effects driving the ultimate progression of overt diabetes. In this study, we characterized the metabolic phenotypes of the adult GIRKO mice acutely switched to high-fat diet (HFD) feeding in order to identify additional metabolic challenges required for disease progression. Distinct from other diet-induced obesity (DIO) and genetic models (e.g., db/db mice), GIRKO mice remained leaner on HFD feeding, but developed other cardinal features of insulin resistance syndrome. GIRKO mice rapidly developed hyperglycemia despite compensatory increases in β-cell mass and hyperinsulinemia. Furthermore, GIRKO mice also had impaired oral glucose tolerance and a limited glucose-lowering benefit from exendin-4, suggesting that the blunted incretin effect contributed to hyperglycemia. Secondly, GIRKO mice manifested severe dyslipidemia while on HFD due to elevated hepatic lipid secretion, serum triglyceride concentration, and lipid droplet accumulation in hepatocytes. Thirdly, GIRKO mice on HFD had increased inflammatory cues in the gut, which were associated with the HFD-induced microbiome alterations and increased serum lipopolysaccharide (LPS). In conclusion, our studies identified important gene/diet interactions contributing to diabetes progression, which might be leveraged to develop more efficacious therapies.     

Involvement of guanylin and GC-C in rat mesenteric macrophages in resistance to a high-fat diet

A high-fat diet (HFD) is a well-known contributing factor in the development of obesity. Most rats fed HFDs become obese. Those that avoid obesity when fed HFDs are considered diet resistant (DR). We performed a microarray screen to identify genes specific to the mesenteric fat of DR rats and revealed high expression of guanylin and guanylyl cyclase C (GC-C) in some subjects. Our histologic studies revealed that the cellular source of guanylin and GC-C is macrophages. Therefore, we developed double-transgenic (Tg) rats overexpressing guanylin and GC-C in macrophages and found that they were resistant to the effects of HFDs. In the mesenteric fat of HFD-fed Tg rats, Fas and perilipin mRNAs were downregulated, and those of genes involved in fatty acid oxidation were upregulated, compared with the levels in HFD-fed wild-type rats. In vitro studies demonstrated that lipid accumulation was markedly inhibited in adipocytes cocultured with macrophages expressing guanylin and GC-C and that this inhibition was reduced after treatment with guanylin- and GC-C-specific siRNAs. Our results suggest that the macrophagic guanylin-GC-C system contributes to the altered expression of genes involved in lipid metabolism, leading to resistance to obesity.     

Protein malnutrition mitigates the effects of a high-fat diet on glucose homeostasis in mice

Nutrient malnutrition, during the early stages of development, may facilitate the onset of metabolic diseases later in life. However, the consequences of nutritional insults, such as a high-fat diet (HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers of mitochondrial function in the gastrocnemius muscle of protein-restricted mice fed an HFD until early adulthood. Male C57BL/6 mice were fed a control (14% protein-control diet) or a protein-restricted (6% protein-restricted diet) diet for 6 weeks. Afterward, mice received an HFD or not for 8 weeks (mice fed a control diet and HFD [CH] and mice fed a protein-restricted diet and HFD [RH]). RH mice showed lower weight gain and fat accumulation and did not show an increase in fasting plasma glucose and insulin levels compared with CH mice. RH mice showed higher energy expenditure, increased citrate synthase, peroxisome-proliferator-activated receptor gamma coactivator 1-alpha protein content, and higher levels of malate and α-ketoglutarate compared with CH mice. Moreover, RH mice showed increased AMPc-dependent kinase and acetyl coenzyme-A (CoA) carboxylase phosphorylation, lower intramuscular triacylglycerol content, and similar malonyl-CoA levels. In conclusion, protein undernourishment after weaning does not potentiate fat accumulation and insulin resistance in adult young mice fed an HFD. This outcome seems to be associated with increased skeletal muscle mitochondrial oxidative capacity and reduced lipids accumulation.     

山楂总黄酮联合茶多酚对高脂膳食大鼠血脂及氧化应激的影响

为了探讨山楂总黄酮联合茶多酚对高脂膳食大鼠血脂及氧化应激的影响。将山楂总黄酮联合茶多酚灌胃高脂膳食大鼠5周,取血测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C);并测血清及肝组织丙二醛(MDA)、超氧化物歧化酶(S0D)、谷胱甘肽过氧化物酶(GSH-Px);计算肝指数及进行肝病理组织学观察。结果发现,与模型组相比,山楂总黄酮联合茶多酚组大鼠血清TC、TG、LDL-C水平显著下降,血清HDL-C水平显著升高,血清及肝组织MDA显著降低,S0D、GSH-Px活力明显升高,肝指数明显降低,肝细胞脂肪化程度明显减轻。表明山楂总黄酮联合茶多酚增强了高脂饮食大鼠的抗氧化水平,调节了脂质紊乱。