Effect of fish oil and coconut oil diet on the LDL receptor activity of rat liver plasma membranes

The influence of 4 weeks treatment with fish oil and coconut oil enriched diets on the chemical composition of rat liver plasma membranes and LDL and on the binding of LDL to liver membranes was investigated. Rats fed fish oil diet showed a total, LDL and HDL plasma cholesterol concentration lower than the values observed in rats fed coconut oil and to a lesser extent lower than those of rats fed standard laboratory diet. LDL of rats on fish oil diet had a relative percentage of cholesterol and phospholipid lower, while that of triacylglycerol was greater. Furthermore, fish oil feeding was associated with a greater concentration of n - 3 fatty acids and a lower arachidonic and linoleic acid content in LDL. Liver plasma membranes isolated from fish oil rats showed a higher percentage of n - 3 fatty acids, while only a trace amount of these fatty acids was found in control and coconut oil fed animals. In binding experiments performed with LDL and liver membranes from fish oil fed rats and control rats, binding affinity (Kd = 3.47 +/- 0.93 and 4.56 +/- 1.27, respectively) was significantly higher (P less than 0.05) as compared to that found using membranes and lipoprotein from coconut oil fed rats (Kd = 6.82 +/- 2.69). In cross-binding experiments performed with fish oil LDL and coconut oil liver plasma membranes or coconut oil LDL and fish oil liver plasma membranes, the LDL binding affinity was comparable and similar to that found in fish oil fed animals. No difference was found in the Bmax among all the groups of binding experiments. Our data seem to indicate that during fish oil diet the higher binding affinity of LDL to liver plasma membranes might be partly responsible of the hypocholesterolemic action of marine oil rich diet as compared to saturated diet. Furthermore, the modifications of binding affinity induced by changes of LDL and membrane source, suggest that lipoprotein and liver plasma membrane composition may be an important variable in binding studies.     

Possible Role of Triacylglycerol-Rich Lipoproteins in the Down-Regulation of Adipose Obese mRNA Expression in Rats Re-Fed a High-Fat Diet

Summary The large amount of absorbed dietary lipid after feeding a high-fat diet is mainly transported as triacylglycerol (TG)-rich lipoproteins (TRL) in the post-prandial blood and is subsequently distributed to peripheral tissues including adipose and muscle tissues. An in vivo and an in vitro study were conducted to investigate the possible role of post-prandial TRL after high fat feeding in the regulation of obese (ob) gene expression. Adult male Wistar rats were fasted for 48 h and re-fed either a fat-free/high-carbohydrate diet or a high-fat diet for 2, 4, or 8 h and plasma glucose, insulin, TG, and leptin as well as ob mRNA expression in epididymal fat pads were examined. Rats re-fed the high-fat diet had significantly higher plasma TG (p<0.05) and lower plasma leptin and adipose ob mRNA (p<0.05) than those fed the fat-free/high-carbohydrate diet; however, plasma glucose and insulin concentrations were not significantly different between the two groups. Plasma lipid analysis found large amount of TRL in rats fed with high-fat diet; however, only very small amount of the TRL was found in rats fed with fat-free/high-carbohydrate diet. We speculated that TRL might involve in regulation of ob gene expression. To further examine the regulation of TRL on ob mRNA expression, differentiated 3T3-L1 adipocytes were treated with TRL collected from rats fed 5 ml soybean oil by gastric intubations. TRL down-regulated ob mRNA not only in a dose and time dependent manner but also in the presence of insulin in 3T3-L1 adipocytes. These results suggest a possible role of TRL in the down-regulation of adipose ob mRNA expression and may account, at least in part, for the previous observations that short-term high fat feeding resulted in lower plasma leptin.     

Beneficial influence of dietary curcumin, capsaicin and garlic on erythrocyte integrity in high-fat fed rats

In rats rendered hyperlipidemic by maintaining them on a high-fat diet (30%) for 8 weeks, inclusion of spice principles [curcumin (0.2%) or capsaicin (0.015%)] or garlic (2.0%) in the diet produced significant hypotriglyceridemic effect. Plasma cholesterol remained unaffected in high-fat treatment. Hepatic triglyceride content was significantly higher in high-fat fed rats, and this increase was effectively countered by inclusion of the hypolipidemic spice agents -- curcumin, capsaicin or garlic in the diet. The lipid profile of erythrocyte membranes of hyperlipidemic rats was similar to basal controls. An examination of the osmotic fragility of erythrocytes in various groups indicated that the red blood cells of hyperlipidemic rats display a slight resistance to osmotic lysis. Inclusion of spice principles [curcumin (0.2%) or capsaicin (0.015%)] or garlic (2.0%) in the diet, which produced the hypotriglyceridemic effect, appeared to beneficially correct this altered osmotic fragility of erythrocytes. Activities of ouabain-sensitive Na(+),K(+)-ATPase as well as acetylcholinesterase of erythrocyte membranes in high-fat fed rats remained unaltered. Activity of Ca(2+),Mg(2+)-ATPase in erythrocyte membrane was significantly decreased in high-fat fed animals, whereas dietary spice principles and garlic countered this reduction in enzyme activity. In the absence of any change in the cholesterol/phospholipid molar ratio in the erythrocyte membrane, a decreased activity of membrane-bound Ca(2+),Mg(2+)-ATPase could have probably contributed to the accumulation of intracellular calcium leading to the diminished deformability of the erythrocytes in high-fat fed rats.     

The effect of dietary fat on lipogenesis in mammary gland and liver from lactating and virgin mice

1. Virgin and lactating C(3)H mice maintained on laboratory chow were transferred to a high-fat (15% corn oil) or a fat-free diet 3 days before being killed. 2. The linoleate content of liver, mammary gland and milk was decreased in lactating mice given the fat-free diet but was increased in those fed on the high-fat diet. Changes in linoleate content and mammary gland followed a similar but much less marked trend in virgin animals. 3. Hepatic fatty acid synthesis in lactating and virgin mice fed on the fat-free diet was higher than in corresponding animals fed on either the chow or the high-fat diet. The lipogenic capacity of livers from mice fed on either the chow or the high-fat diet was greater in lactating than in virgin animals. These changes in hepatic lipogenic capacity were accompanied by alterations in the specific activities of certain enzymes involved in fat synthesis. 4. Mammary gland from virgin and lactating animals showed no such adaptation to dietary fat. Results indicate that fatty acid synthesis in neither mammary-gland parenchymal cells nor mammary-gland adipose cells can be influenced by dietary fat in the same way as in the hepatocyte.     

Hepatic uptake of chylomicrons and triglyceride emulsions in rats fed diets of differing fat content

The hepatic removal of plasma chylomicrons was determined for rats fed the following diets: a) containing no triglyceride, b) regular chow diet with 4.5% of its mass as lipid and, c) a corn oil-supplemented chow with triglyceride accounting for 20% of the mass. The fractional hepatic uptake of either radiolabeled chylomicrons or a triglyceride emulsion was reciprocally related to the amount of lipid in the diet. The animals receiving only carbohydrate and protein calories had the most active hepatic uptake of particulate triglyceride and were observed to have a significant decrease in the plasma concentration of the C apolipoproteins. The addition of either C-I, C-II, or C-III apoproteins to the triglyceride emulsion prior to intravenous injection produced a significantly lower hepatic triglyceride recovery of emulsions containing apoC-III. When the plasma of animals fed a fat-free diet was supplemented with human C-III-1 apolipoprotein, the distribution into the liver of either enterally administered fatty acid or parenteral triglyceride was diminished. The triglyceride content in the liver of the rats fed fat-free or corn oil-supplemented diets was significantly greater than that of the control rats and composition was somewhat similar to that of lymph triglyceride. The studies indicate an important influence of dietary lipid on both the partition of plasma triglyceride into the liver and the steady state hepatic triglyceride content.     

激光生物学技术研究高脂血症大鼠红细胞变形能力改变及其机制

目的:通过研究红细胞膜流动性以及红细胞骨架结构的改变,进一步探讨高脂血症大鼠红细胞变形能力改变的机制。方法:16只Wistar大鼠随机分为两组:高血症组和对照组。高脂组给予高脂饮食。16周后,腹主动脉采血,采用酶比色法检测血浆甘油三脂、胆固醇含量;并利用激光衍射法测定红细胞变形指数、取向指数,荧光偏振法测定红细胞膜流动性,激光共聚焦显微镜观测红细胞骨架改变和红细胞F-actin的含量。结果:发现高脂血症大鼠红细胞的变形指数、取向指数以及红细胞膜的流动性显著降低(P<0.05),红细胞形态和骨架发生改变,F-actin含量显著降低(P<0.05)。结论:高脂血症大鼠红细胞变形能力降低与红细胞膜结构改变有一定的关系。     

Beneficial effects of alpha linolenic acid rich flaxseed oil on growth performance and hepatic cholesterol metabolism in high fat diet fed rats

The purpose of the study was to investigate the effect of flaxseed oil (FO), rich in alpha-linolenic acid (ALA) (18:3 n-3) on growth parameters and lipid metabolism of rats fed with high fat diet. High fat diet (HFD) resulted in significant alterations in hepatic lipids, increase in body weight gain and negative effect on lipoprotein metabolism. FO supplementation significantly lowered the increase in body weight gain, liver weight, plasma cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoprotein (HDL), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein (VLDL), LDL/HDL and TC/HDL ratio in HFD fed rats. FO significantly reduced the hepatic and plasma lipid levels indicating its hypolipidemic activity. On the other hand, oral administration of FO exhibited lower plasma lipoprotein profile as compared to HFD rats. Hepatic protection by FO is further substantiated by the normal liver histological findings in HFD fed rats. These data suggest that FO participate in the normal regulation of plasma lipid concentration and cholesterol metabolism in liver. No adverse effect of FO on growth parameters and plasma lipids in rats fed with fat-free diet. The results of the present study demonstrate that FO may be developed as a useful therapy for hyperlipidemia through reducing hepatic lipids, thereby proving its hypolipidemic activity.     

Activation of branched-chain alpha-keto acid dehydrogenase complex by exercise: effect of high-fat diet intake

The effect of exercise on the activity of branched-chain alpha-keto acid dehydrogenase complex in liver and muscle was studied in rats fed a high-fat (FAT) or a high-carbohydrate (CHO) diet. Both diet groups of rats were offered isoenergetic diets by a meal-feeding method and were trained by treadmill running. On the final day of the experiment, half of the rats in each diet group were exercised by 2 h of running just before they were killed. The activity state of the enzyme complex was elevated maximally by exercise in liver of rats fed the FAT diet but not in liver of rats fed the CHO diet, suggesting that catabolism of branched-chain amino acids in rat liver during exercise was enhanced by the FAT diet. The activity state of the enzyme complex in muscle was enhanced by exercise in both groups of rats, but a significant difference was not observed between the groups. The concentration of branched-chain amino acids was elevated in liver and muscle by exercise in both groups of rats, but the elevated levels in liver were lower in rats fed the FAT diet than in those fed the CHO diet. Serum branched-chain amino acid concentrations were significantly lower in rested rats fed the FAT diet than in those fed the CHO diet, and the leucine and isoleucine concentrations in the former were elevated by exercise, but the serum concentrations in the latter were not significantly affected by exercise. ATP and ADP concentrations in muscle were not significantly affected by either diet or exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of diet composition on coenzyme A and its thioester pools in various rat tissues

Three coenzyme A (CoA) molecular species, i.e., acetyl-CoA, malonyl-CoA, and nonesterified CoA (CoASH), in 13 types of fasted rat tissue were analyzed. A relatively larger pool size of total CoA, consisting of acetyl-CoA, malonyl-CoA, and CoASH, was observed in the medulla oblongata, liver, heart, and brown adipose tissue. Focusing on changes in the CoA pool size in response to the nutrient composition of the diet given, total CoA pools in rats continuously fed a high-fat diet for 4 weeks were significantly higher in the hypothalamus, cerebellum, and kidney, and significantly lower in the liver and skeletal muscle than those of rats fed a high-carbohydrate or high-protein diet. In particular, reductions in the liver were remarkable and were caused by decreased CoASH levels. Consequently, the total CoA pool size was reduced by approximately one-fifth of the hepatic contents of rats fed the other diets. In the hypothalamus, which monitors energy balance, all three CoA molecular species measured were at higher levels when rats were fed the high-fat diet. Thus, it was of interest that feeding rats a high-fat diet affected the behaviors of CoA pools in the hypothalamus, liver, and skeletal muscle, suggesting a significant relationship between CoA pools, especially malonyl-CoA and/or CoASH pools, and lipid metabolism in vivo.     

Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats

In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg. kg(-1). day(-1) sc), or food restriction (HF-FR) for 12-15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulin-stimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic beta-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.     

The in vitro stability of rat liver glucose-6-phosphate dehydrogenase as a function of diet

Rat liver glucose-6-phosphate dehydrogenase (G6PD) activity was studied in starved-refed rats given diets containing three levels of fat (35%, high-fat; 5%, low-fat; 0%, fat-free). Elution characteristics from DEAE-cellulose, Km for glucose-6-phosphate, pH optimum, and molecular weight appeared to be similar. During storage or heat denaturation, stability apparently was lowest of G6PD of livers from rats refed the high-fat diet. Heat stability was enhanced by the addition of NADP, but some differences due to diet persisted. Titration of a constant amount of enzyme with heating gave inconsistent results: in two of four experiments rats refed the high-fat diet had an equivalence point twice that of rats refed the fat-free diet. This difference disappeared if the antibody titration was carried out in the cold. The diet-induced instability of the G6PD, as measured in vitro, was reversible by changing the diet of the rats.     

Ameliorating effect and potential mechanism of Rehmannia glutinosa oligosaccharides on the impaired glucose metabolism in chronic stress rats fed with high-fat diet

The aim of this study was to determine whether the Rehmannia glutinosa oligosaccharides (ROS) ameliorate the impaired glucose metabolism and the potential mechanism in chronic stress rats fed with high-fat diet. The rats were fed by a high-fat diet and simultaneously stimulated by chronic stress over 5 weeks. Body weight, fasting plasma glucose, intraperitoneal glucose tolerance test (IPGTT), plasma lipids, gluconeogenesis test (GGT), glycogen content, and corticosterone, insulin and leptin levels were measured. The results showed that ROS administration (100, 200 mg/kg, i.g.) for 5 weeks exerted the effects of increasing the organ weights of thymus and spleen, lowering the fasting plasma glucose level, improving impaired glucose tolerance, increasing the contents of liver and muscle glycogen, decreasing the gluconeogenesis ability, plasma-free fatty acid's level, as well as plasma triglyceride and total cholesterol levels in chronic stress and high-fat fed rats, especially in the group of 200 mg/kg; while the plasma corticosterone level was decreased, and plasma leptin level was increased. These results suggest that ROS exert an ameliorating effect of impaired glucose metabolism in chronic stress rats fed with high-fat diet, and the potential mechanism may be mediated through rebuilding the glucose homeostasis in the neuroendocrine immuno-modulation (NIM) network through multilinks and multitargets.     

Effect of taurine on cholesterol metabolism in hamsters: up-regulation of low density lipoprotein (LDL) receptor by taurine

The effects of taurine on hepatic cholesterol metabolism were investigated in hamsters fed a high-fat diet or normal chow. Two weeks-treatment of taurine at 1% in drinking water prevented high-fat diet-induced increase in cholesterol levels of serum and liver. The decrease in serum cholesterol by taurine was due to decrease in non-HDL cholesterols. A similar tendency was noted in serum and liver cholesterol levels of hamsters fed a normal diet. In hamsters fed a high-fat diet, taurine prevented elevation in hepatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and increased the activity of cholesterol 7alpha-hydroxylase. Taurine also increased cholesterol 7alpha-hydroxylase activity in hamsters fed normal chow. Studies on liver membranes revealed that taurine increased 125I-labeled LDL binding by 52% and 58% in hamsters fed either a normal chow or high-fat diet, respectively. Furthermore, LDL kinetic analysis showed that taurine intake resulted in significant faster plasma LDL fractional catabolic rates (FCR). These results suggest that taurine elevates hepatic LDL receptor and thereby decreases serum cholesterol levels, an event which may be the result of hepatic cholesterol depletion as a consequence of increased bile acid synthesis via enhancement of cholesterol 7alpha-hydroxylase activity. Thus, up-regulation of the LDL receptor and subsequent increase in receptor- mediated LDL turnover may be a key event in the cholesterol-lowering effects of taurine in hamsters.     

The effect of high-fat diet on plasma ghrelin and leptin levels in rats

Ghrelin and leptin regulate appetite and energy homeostasis in humans and rodents. The effects of different nutritional factors on ghrelin and leptin secretion are not well documented in rats. Therefore, the aim of our study was to investigate the effect of a high-fat diet on plasma ghrelin and leptin levels and on adiposity. Twenty male Wistar rats, body weight220–260 g, were used in the study. Rats were randomized either on a standard chow diet (n=10) or on a high-fat diet (a mixture of nuts) forad libitum 11-week period. Body weight was measured once per week. At the end of the nutritional period, rats were sacrificed. Blood was collected for determination of lipids and glucose, as well as plasma ghrelin and leptin levels by ELISA method. The weight of different organs was determined. Rats fed on a high-fat diet showed significant increase in total body weight compared to control group. The long-term intake of high-fat diet caused hyperleptinemia and hypoghrelinemia. There was a significant positive correlation between plasma leptin levels and epididymal fat mass, liver and heart. In contrast, ghrelin levels showed inverse correlation with epididymal fat mass and liver weight. In conclusion, long-term intake of high-fat diet induced changes in plasma ghrelin and leptin in male rats, as well as in epididymal fat mass, liver and heart weights.     

Chronic ethanol administration alters hepatic surface membranes as evidenced by decreased concanavalin A binding

The effects of chronic ethanol administration on the hepatic surface membrane were examined. The binding of the lectin, concanavalin A (Con A), to isolated hepatocytes was used to ascertain changes in the hepatic plasma membrane, especially in regard to glycoprotein composition, due to chronic ethanol feeding. Hepatocytes, isolated from rats fed ethanol for 5 to 7 weeks, had a decreased ability to bind Con A when compared to hepatocytes from either the pair-fed controls or ad libitum chow-fed rats. Since decreased Con A binding was more apparent at high Con A concentrations, reduced lectin binding likely reflected changes in the composition of surface membrane glycoproteins in the livers of the ethanol-fed rats. When ethanol (50 mM) was added to the incubation medium containing hepatocytes from ethanol-fed rats, pair-fed controls, or chow-fed rats, no effects on Con A binding were observed. These results indicate that chronic ethanol administration induces changes in the oligosaccharide chains of plasma membrane glycoproteins in the liver. Such alterations may play a role in the pathogenesis of alcoholic liver disease.     

The effects of boron-supplemented diets on adipogenesis-related gene expressions,anti-inflammatory,and antioxidative response in high-fat fed rats

The fatty liver syndrome caused by nutritional factors is a common cause of hepatic dysfunction globally. This research was designed to study the shielding effect of boron in rats fed a diet having high fat. Overall, 40 Wistar albino male rats were placed into one control and four treatment groups, that is, each having eight rats. Group I was provided with a standard rat diet while group II was only provided a high-fat diet for 60 days. Groups III, IV, and V were provided with 5, 10, and 20 mg/kg/day boron, respectively, by gastric gavage besides a high-fat diet for 60 days. Malondialdehyde was increased significantly in rats' blood and tissue because of high-fat diets. Glutathione was decreased significantly in blood and tissues because of a high-fat diet. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were decreased in the blood and tissues of the high-fat-fed rats. The genes expression for C-reactive protein, interleukin-1β, leptin, and tumor necrosis factor-α were increased while gene expression for peroxisome proliferator-activated receptors was decreased in the liver of rats fed with a high-fat diet. Contrariwise, boron supplementation improves antioxidative response in terms of increased SOD and CAT activities, gene expression regulation, and improved anti-inflammatory activities. In a nutshell, boron has dose-dependent shielding antioxidative and tissue regenerative effects in rats.     

Rosiglitazone and fenofibrate improve insulin sensitivity of pre-diabetic OLETF rats by reducing malonyl-CoA levels in the liver and skeletal muscle

AimsRosiglitazone and fenofibrate, specific agonists of the peroxisome proliferator activated receptors-γ (PPARγ) and -α (PPARα), respectively, improve insulin sensitivity in diabetic animals and in patients with type 2 diabetes. Here we investigated how pre-diabetic Otsuka Long–Evans Tokushima Fatty (OLETF) rats fed with normal and high-fat diets respond to these PPAR agonists.Main methodsPre-diabetic OLETF rats were subjected to high-fat or standard diets with or without rosiglitazone or fenofibrate for 2 weeks. The metabolism of the rats and the levels of malonyl-CoA and activities of malonyl-CoA decarboxylase (MCD), acetyl-CoA carboxylase (ACC), and AMP-activated protein kinase (AMPK) in metabolic tissues were assessed.Key findingsRosiglitazone and fenofibrate significantly improved insulin sensitivity and reduced the levels of plasma triglycerides and free fatty acids in OLETF rats fed with a high-fat diet. Fenofibrate particularly reduced the body weight, fat, and total cholesterol in high fat diet OLETF rats. The highly elevated malonyl-CoA levels in the skeletal muscle and liver of OLETF rat were significantly reduced by rosiglitazone or fenofibrate due to, in part, the increased MCD activities and expression. On the other hand, ACC activities were unchanged in skeletal muscle and decreased in liver in high fat diet group. AMPK activities were dramatically decreased in OLETF rats and not affected by these agonists.SignificanceThese results demonstrate that treatment of pre-diabetic OLETF rats–particularly those fed a high-fat diet–with rosiglitazone and fenofibrate significantly improves insulin sensitivity and fatty acid metabolism by increasing the activity of MCD and reducing malonyl-CoA levels in the liver and skeletal muscle.     

Increased hepatic activity of inducible nitric oxide synthase in rats fed on a high-fat diet

The effects were examined of the dietary level of fat on the activity of inducible nitric oxide synthase (iNOS) in the liver of rats. In experiment 1, rats were fed on a diet containing 5% or 20% beef tallow or safflower oil for 32 d. The animals were given a subcutaneous injection of the carcinogen, 1,2-dimethylhydrazine (DMH), on d 4. The activity of hepatic iNOS was significantly elevated by the high-fat diet, but was unaffected by the dietary source of the fat examined. In experiment 2, rats were fed on a 5% or 20% beef tallow diet for 11 d or 32 d with or without the DMH treatment. Feeding the high-fat diet and DMH treatment caused higher activity of hepatic iNOS. In experiment 3, the high-fat diet elevated hepatic iNOS activity and the amount of its protein in the lipopolysaccharide-treated rats. The results suggest that hepatic NO production is enhanced by a high-fat diet.     

L-histidine induced changes in adenosine 3':5'-monophosphate levels in rat brain and amounts of apo-, holo-a and holo-b fatty acid synthetases in rat liver.

When fasted rats were fed a chow or fat-free diet supplemented 5% with L-histidine for three days, the brain adenosine 3′:5′-monophosphate (cAMP) level increased. A 50% increase occurred in rats fed a chow diet and 20% increase in rats fed a fat-free diet. Purification of liver fatty acid synthetase and the isolation of liver apo-, holo-$\text{a}$ and holo-$\text{b}$ fatty acid synthetases demonstrated that L-histidine feeding caused changes in the relative amounts of these enzymes. Apo- and holo-$\text{b}$ fatty acid synthetases increased while the holo-$\text{a}$ form simultaneously decreased. This effect was observed in rats fed either chow or fat-free diets supplemented with L-histidine.     

Roles of plasma interleukin-6 and tumor necrosis factor-alpha and FFA and TG in the development of insulin resistance induced by high-fat diet

The role of adipokines in development of insulin resistance still remains controversial. The purpose of the present study was to examine the dynamic changes of fasting plasma levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), free fatty acids (FFA) and insulin in a Sprague-Dawley rat insulin resistant model induced by high-fat diet. Heterotopic deposition of triglycerides (TG) in liver, skeletal muscles and pancreatic islet was also investigated. The fasting plasma level of insulin in rats in the high-fat diet group was significantly higher than that in the normal diet group on day 21 (P<0.01), suggesting that an increased insulin resistance developed in the high-fat diet group. However, no significant difference in the plasma IL-6 level was observed between the two groups (P>0.05), although in both groups, the plasma IL-6 level was significantly higher on day 21 than that of the day 0 (P<0.05). The plasma FFA level in the high-fat diet group began to increase significantly on day 21 (P<0.05), and elevated markedly on day 28, was positively correlated to the fasting plasma insulin level. Histological study revealed a more abundant TG deposition in liver and skeletal muscles (from quadriceps femoris) in the high-fat diet group than in the normal diet group on day 21, and the liver deposition was even higher on day 28. However, no deposition was observed in pancreatic islets. The plasma TNF-alpha level remained unchanged throughout the duration of the experiment. These results indicate that the progression of insulin resistance in high-fat diet rats is closely related to the plasma FFA elevation and the heterotopic deposition of TG in liver and skeletal muscles, but is unrelated to the plasma TNF-alpha and IL-6 levels.