Rutin attenuates metabolic changes, nonalcoholic steatohepatitis, and cardiovascular remodeling in high-carbohydrate, high-fat diet-fed rats

Metabolic syndrome (obesity, diabetes, and hypertension) increases hepatic and cardiovascular damage. This study investigated preventive or reversal responses to rutin in high-carbohydrate, high-fat diet-fed rats as a model of metabolic syndrome. Rats were divided into 6 groups: 2 groups were fed a corn starch-rich diet for 8 or 16 wk, 2 groups were fed a high-carbohydrate, high-fat diet for 8 or 16 wk, and 2 groups received rutin (1.6 g/kg diet) in either diet for the last 8 wk only of the 16-wk protocol. Metabolic changes and hepatic and cardiovascular structure and function were then evaluated in these rats. The corn starch-rich diet contained 68% carbohydrate (mainly cornstarch) and 0.7% fat, whereas the high-carbohydrate, high-fat diet contained 50% carbohydrate (mainly fructose) and 24% fat (mainly beef tallow) along with 25% fructose in drinking water (total 68% carbohydrate using mean food and water intakes). The high-carbohydrate, high-fat diet produced obesity, dyslipidemia, hypertension, impaired glucose tolerance, hepatic steatosis, infiltration of inflammatory cells in the liver and the heart, higher cardiac stiffness, endothelial dysfunction, and higher plasma markers of oxidative stress with lower expression of markers for oxidative stress and apoptosis in the liver. Rutin reversed or prevented metabolic changes such as abdominal fat pads and glucose tolerance, reversed or prevented changes in hepatic and cardiovascular structure and function, reversed oxidative stress and inflammation in the liver and heart, and normalized expression of liver markers. These results suggest a non-nutritive role for rutin to attenuate chronic changes in metabolic syndrome.     

Are brain and heart tissue prone to the development of thiamine deficiency?

Thiamine deficiency is a continuing problem leading to beriberi and Wernicke's encephalopathy. The symptoms of thiamine deficiency develop in the heart, brain and neuronal tissue. Yet, it is unclear how rapid thiamine deficiency develops and which organs are prone to development of thiamine deficiency. We investigated these issues in a thiamine deficient animal model. Twenty-four male Lewis rats were fed a thiamine deficient diet, which contained 0.04% of normal thiamine intake. Six control rats were fed 200 μg of thiamine per day. Every week a group of six rats on the thiamine-deficient diet was sacrificed and blood, urine and tissue were stored. Blood and tissue transketolase activity, thiamine and thiamine metabolites were measured and PCR of thiamine transporter-1 (ThTr-1) was performed. Transketolase activity was significantly reduced in red blood cells, liver, lung, kidney and spleen tissue after two weeks of thiamine deficient diet. In brain tissue, transketolase activity was not reduced after up to four weeks of thiamine deficient diet. The amount of thiamine pyrophosphate was also significantly conserved in brain and heart tissue (decrease of 31% and 28% respectively), compared to other tissues (decrease of ∼70%) after four weeks of thiamine deficient diet. There was no difference between tissues in ThTr-1 expression after four weeks of thiamine deficient diet. Despite the fact that the heart and the brain are predilection sites for complications from thiamine deficiency, these tissues are protected against thiamine deficiency. Other organs could be suffering from thiamine deficiency without resulting in clinical signs of classic thiamine deficiency in beriberi and Wernicke's encephalopathy.     

Dietary effect of pomegranate seed oil rich in 9cis, 11trans, 13cis conjugated linolenic acid on lipid metabolism in obese,hyperlipidemic OLETF Rats

Conjugated fatty acid, the general term of positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds, has attracted considerable attention because of its potentially beneficial biological effects. In the present study, dietary effect of pomegranate seed oil rich in punicic acid (9 cis, 11 trans, 13 cis -conjugated linolenic acid; 9c, 11t, 13c-CLNA) on lipid metabolism was investigated in obese, hyperlipidemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After 2 weeks feeding period, OLETF rats revealed obesity and hyperlipidemia compared with their progenitor LETO rats. Feeding of the diet supplemented with 9% safflower oil and 1% pomegranate seed oil (9c, 11t, 13c-CLNA diet) did not affect abdominal white adipose tissue weights and serum lipid levels compared with the diet supplemented with 10% safflower oil (control diet) in OLETF rats. However, the accumulated hepatic triacylglycerol was markedly decreased by 9c, 11t, 13c-CLNA diet in OLETF rats. Activities of hepatic enzymes related to fatty acid synthesis and fatty acid β-oxidation were not altered by 9c, 11t, 13c-CLNA diet. Levels of monounsaturated fatty acid (MUFA), major storage form of fatty acid, in serum triacylglycerol were markedly higher in obese, hyperlipidemic OLETF rats than in lean LETO rats. In addition, 9c, 11t, 13c-CLNA diet significantly decreased MUFA levels in OLETF rats. This is the first study showing that 9c, 11t, 13c-CLNA suppresses delta-9 desaturation in vivo, and we suggest that the alleviation of hepatic triacylglycerol accumulation by 9c, 11t, 13c-CLNA diet was, at least in part, attributable to the suppression of delta-9 desaturation in OLETF rats.     

Functional lipids and the prevention of the metabolic syndrome

The metabolic syndrome is increasingly prevalent in worldwide. The quality and quantity of dietary lipids could be important modulators associated with the cardiovascular morbidity and mortality. At present, functional lipids such as conjugated linoleic acid (CLA) and phospholipids have attracted considerable attention because of their beneficial biological effects in attenuating metabolic syndrome. Supplementation of CLA reduces abdominal white adipose tissues, serum triacylglycerol (TAG) level, and liver TAG level in obese Otsuka Long-Evans Tokushima Fatty OLETF rats. These effects were attributed to enhanced fatty acid beta-oxidation and suppressed fatty acid synthesis in the liver. In addition, CLA enhanced energy expenditure in these rats. Anti-hypertensive properties of CLA have also been demonstrated. In obese/diabetic OLETF and Zucker rats, feeding of CLA prevented the development of obesity-induced hypertension. This was associated with an altered production of physiologically active adipocytokines, such as adiponectin, leptin and angiotensinogen. In addition, CLA could alleviate the development of insulin resistance and fatty liver. Dietary phospholipids have physiological functions that are different to dietary TAG. We recently reported that phosphatidylcholine (PC) alleviated orotic acid-induced fatty-liver through the suppression of hepatic lipogenesis in rats, and omega 3-PC from salmon roe prevented the development of obesity-related diseases through the suppression of lipogenic gene expressions and the enhancement of lypolytic gene expressions in the liver of obese rats. However, reports which studying the nutritional functions of minor phospholipids, such as phosphatidylinositol (PI), are scarce. Our study indicated that dietary PI lowered lipids in the plasma and liver by suppressing hepatic TAG synthesis.     

G protein-coupled receptors: Key molecules in metabolic associated fatty liver disease development

Metabolic associated fatty liver disease (MAFLD) is a range of hepatic disorders with progression to steatohepatitis with risk of development of fibrosis, cirrhosis, and hepatocellular carcinoma. MAFLD is strongly related to metabolic disorders of active fatty acids, which seem to be selective according to their specific ligand of G protein-coupled receptors (GPRs) located in immune response cells. An approach to study the pathophysiological mechanisms of MAFLD could be through the expression of active fatty acids ligands. The expression of GPRs is associated with obesity, microbiota environment, and dietary characteristics in patients with MAFLD. More specifically, GPR41, GPR43, GPR20, and GPR120 have been associated with alteration of lipid metabolism in hepatic and intestinal cells, and consequently they have a key role in metabolic diseases. We observed that GPR120 is not expressed in nonoverweight/obese patients, regardless of the presence of MAFLD; meanwhile the expression of GPR41 is increased in patients with lean MAFLD. GPRs role in liver disease is intriguing and a field of research opportunity. More studies are necessary to define the role of active fatty acids in the development of metabolic diseases.     

The diurnal rhythm of energy expenditure differs between obese and glucose-intolerant rats and streptozotocin-induced diabetic rats

Otsuka Long Evans Tokushima Fatty (OLETF) rats were developed as a model of noninsulin-dependent diabetes mellitus (NIDDM) with mild obesity. Changes in carcass composition and in the daily profile of energy expenditure were examined before and after manifestation of diabetes (8 and 24 wk, respectively), and compared with the normal control Long Evans Tokushima (LETO) rats and streptozotocin (STZ)-induced diabetic LETO rats. OLETF rats had greater body weights than LETO rats and significantly greater absolute and relative fat weights. A diurnal rhythm of energy expenditure associated with two peaks was observed in LETO rats, but the two peaks were not apparent in OLETF rats at 24 wk of age. A diurnal rhythm associated with one peak was observed in STZ-induced diabetic LETO rats. Energy derived from fat constituted this peak; the pattern of the daily energy expenditure was significantly different from that of either nontreated LETO or OLETF rats at 24 wk of age. NIDDM in OLETF rats at 24 wk of age has only a small role in modification of the diurnal rhythm of energy expenditure, whereas STZ-induced diabetes significantly affected the rhythm.     

雄激素在多囊卵巢综合征合并非酒精性脂肪性肝病中的研究进展

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄期妇女常见的生殖内分泌紊乱性疾病,且常伴肥胖、胰岛素抵抗(insulin resistance,IR)和脂代谢紊乱等代谢异常.非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是常见的慢...     

INTRACELLULAR DISTRIBUTION OF THIAMINE IN NORMAL AND THIAMINE DEFICIENTS RATS

Thiamine deficiency caused a relatively uniform depletion of thiamine from subcellular fractions of rat liver, brain, and kidney.     

Metabolic Effects of Vitamin B1 Therapy under Overnutrition and Undernutrition Conditions in Sheep

As a precursor for a universal metabolic coenzyme, vitamin B1, also known as thiamine, is a vital nutrient in all living organisms. We previously found that high-dose thiamine therapy prevents overnutrition-induced hepatic steatosis in sheep by enhancing oxidative catabolism. Based on this capacity, we hypothesized that thiamine might also reduce whole-body fat and weight. To test it, we investigated the effects of high-dose thiamine treatment in sheep under overnutrition and calorie-restricted undernutrition to respectively induce positive energy balance (PEB) and negative energy balance (NEB). Eighteen mature ewes were randomly assigned to three treatment groups (n = 6 each). The control group (CG) was administered daily with subcutaneous saline, whereas the T5 and T10 groups were administered daily with equivoque of saline containing 5 mg/kg and 10 mg/kg of thiamine, respectively. Bodyweight and blood biochemistry were measured twice a week for a period of 22 days under PEB and for a consecutive 30 days under NEB. Surprisingly, despite the strong effect of thiamine on liver fat, no effect on body weight or blood glucose was detectable. Thiamine did, however, increase plasma concentration of non-esterified fatty acids (NEFA) during NEB (575.5 ± 26.7, 657.6 ± 29.9 and 704.9 ± 26.1 µEqL⁻¹ for CG, T5, and T10, respectively: p < 0.05), thereby favoring utilization of fatty acids versus carbohydrates as a source of energy. Thiamine increased serum creatinine concentrations (p < 0.05), which paralleled a trending increase in urea (p = 0.09). This may indicate an increase in muscle metabolism by thiamine. Reduction of fat content by thiamine appears more specific to the liver than to adipose tissue. Additional studies are needed to evaluate the potential implications of high-dose vitamin B1 therapy in muscle metabolism.     

Severe metabolic acidosis and heart failure due to thiamine deficiency

We report the case of a male patient with severe metabolic acidosis and heart failure caused by thiamine deficiency. He was admitted in August 1998 to the Tokai University Oiso Hospital because of severe dyspnea. The patient was diagnosed with heart failure and metabolic acidosis of unknown causes based on arterial blood gas analysis, chest x ray, and ultrasonic echocardiographic examinations. Our previous experience in treating a patient with thiamine deficiency caused by total parenteral nutrition without thiamine supplementation suggested that this patient was deficient in thiamine. The serum thiamine level was low and the lactate level was high. After intravenous administration of thiamine, the acidosis and heart failure disappeared. Dietary analysis showed that thiamine intake was low (0.32 mg/1000 kcal/d). Thiamine deficiency should be included in the differential diagnosis when encountering cases of heart failure with severe metabolic acidosis, even in developed countries.     

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats

ABSTRACT: BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides in fatty liver rats. METHODS: Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA) to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured. RESULTS: Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG) level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphatedehydrogenase (G6PDH) were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c) were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT) in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP) activity was observed in SCC-feeding rats. CONCLUSIONS: These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver.     

Abdominal obesity: metabolic complications and consequences for the liver

Obesity is associated with a number of metabolic and haemodynamic risk factors for cardiovascular disease and type 2 diabetes mellitus. This risk depends on a complex of metabolic and haemodynamic consequences of (visceral) fat accumulation, which probably results from the continuous delivery of fatty acids to the liver via the portal vein. Hypertriglyceridaemia, hyperinsulinaemia, hypertension, insulin resistance and increased hepatic glucose production are all independent risk factors for atherosclerosis. Their combination increases the risk of cardiovascular disease considerably. Triglyceride storage in hepatocytes is another consequence of increased fatty acid supply to the liver. Until recently, hepatic steatosis was considered a harmless condition secondary to obesity or alcoholism. However, it may lead to non-alcoholic hepatic steatosis, which predisposes to liver fibrosis and even cirrhosis.     

A Green Algae Mixture of Scenedesmus and Schroederiella Attenuates Obesity-Linked Metabolic Syndrome in Rats

This study investigated the responses to a green algae mixture of Scenedesmus dimorphus and Schroederiella apiculata (SC) containing protein (46.1% of dry algae), insoluble fibre (19.6% of dry algae), minerals (3.7% of dry algae) and omega-3 fatty acids (2.8% of dry algae) as a dietary intervention in a high carbohydrate, high fat diet-induced metabolic syndrome model in four groups of male Wistar rats. Two groups were fed with a corn starch diet containing 68% carbohydrates as polysaccharides, while the other two groups were fed a diet high in simple carbohydrates (fructose and sucrose in food, 25% fructose in drinking water, total 68%) and fats (saturated and trans fats from beef tallow, total 24%). High carbohydrate, high fat-fed rats showed visceral obesity with hypertension, insulin resistance, cardiovascular remodelling, and nonalcoholic fatty liver disease. SC supplementation (5% of food) lowered total body and abdominal fat mass, increased lean mass, and attenuated hypertension, impaired glucose and insulin tolerance, endothelial dysfunction, infiltration of inflammatory cells into heart and liver, fibrosis, increased cardiac stiffness, and nonalcoholic fatty liver disease in the high carbohydrate, high fat diet-fed rats. This study suggests that the insoluble fibre or protein in SC helps reverse diet-induced metabolic syndrome.     

Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats

Coffee, a rich source of natural products, including caffeine, chlorogenic acid, and diterpenoid alcohols, has been part of the human diet since the 15th century. In this study, we characterized the effects of Colombian coffee extract (CE), which contains high concentrations of caffeine and diterpenoids, on a rat model of human metabolic syndrome. The 8-9 wk old male Wistar rats were divided into four groups. Two groups of rats were fed a corn starch-rich diet whereas the other two groups were given a high-carbohydrate, high-fat diet with 25% fructose in drinking water for 16 wk. One group fed each diet was supplemented with 5% aqueous CE for the final 8 wk of this protocol. The corn starch diet contained ~68% carbohydrates mainly as polysaccharides, whereas the high-carbohydrate, high-fat diet contained ~68% carbohydrates mainly as fructose and sucrose together with 24% fat, mainly as saturated and monounsaturated fat from beef tallow. The high-carbohydrate, high-fat diet-fed rats showed the symptoms of metabolic syndrome leading to cardiovascular remodeling and nonalcoholic fatty liver disease. CE supplementation attenuated impairment in glucose tolerance, hypertension, cardiovascular remodeling, and nonalcoholic fatty liver disease without changing abdominal obesity and dyslipidemia. This study suggests that CE can attenuate diet-induced changes in the structure and function of the heart and the liver without changing the abdominal fat deposition.     

Caffeine attenuates metabolic syndrome in diet-induced obese rats

ObjectiveCaffeine is a constituent of many non-alcoholic beverages. Pharmacological actions of caffeine include the antagonism of adenosine receptors and the inhibition of phosphodiesterase activity. The A₁ adenosine receptors present on adipocytes are involved in the control of fatty acid uptake and lipolysis. In this study, the effects of caffeine were characterized in a diet-induced metabolic syndrome in rats.MethodsRats were given a high-carbohydrate, high-fat diet (mainly containing fructose and beef tallow) for 16 wk. The control rats were given a corn starch diet. Treatment groups were given caffeine 0.5 g/kg of food for the last 8 wk of the 16-wk protocol. The structure and function of the heart and the liver were investigated in addition to the metabolic parameters including the plasma lipid components.ResultsThe high-carbohydrate, high-fat diet induced symptoms of metabolic syndrome, including obesity, dyslipidemia, impaired glucose tolerance, decreased insulin sensitivity, and increased systolic blood pressure, associated with the development of cardiovascular remodeling and non-alcoholic steatohepatitis. The treatment with caffeine in the rats fed the high-carbohydrate, high-fat diet decreased body fat and systolic blood pressure, improved glucose tolerance and insulin sensitivity, and attenuated cardiovascular and hepatic abnormalities, although the plasma lipid concentrations were further increased.ConclusionDecreased total body fat, concurrent with increased plasma lipid concentrations, reflects the lipolytic effects of caffeine in adipocytes, likely owing to the caffeine antagonism of A₁ adenosine receptors on adipocytes.     

Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate,High Fat Diet-Fed Rats

Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats.     

Metabolic syndrome in childhood from impaired carbohydrate metabolism to nonalcoholic fatty liver disease

Compelling evidence supports the concept that nonalcoholic fatty liver disease (NAFLD) represents the hepatic component of metabolic syndrome (MetS). Intrahepatic fat seems to predict more strongly than does visceral adiposity an individual's cardiovascular risk and the likelihood that metabolic abnormalities are present in youth. Young individuals with fatty liver are more insulin resistant and present with a higher prevalence of metabolic abnormalities than do individuals without intrahepatic fat accumulation. They also present with a certain endothelial dysfunction and greater carotid intima-media thickness. Conversely, youth with MetS seem to have an increased risk of developing liver inflammation, a condition termed nonalcoholic steatohepatitis (NASH), and fibrosis. In the context of MetS, the liver is central in that it can drive both hepatic and systemic insulin resistance, trigger low-grade inflammation, and promote atherogenic processes. In the context of MetS, NAFLD and altered carbohydrate metabolism track from childhood to adulthood. Thus, prevention, recognition, and effective treatment of these two abnormalities may limit the burden of morbidity and mortality associated with obesity and may delay onset of cardiovascular disease in early adulthood. The present review aims at systematically presenting evidence of the critical interplay of fatty liver and altered glucose metabolism in youth. It attempts to provide pathogenetic explanations for such an association and the rationale for its treatment, with particular regard to nutritional interventions. Key teaching points: Overweight and obese youth should be screened for fatty liver disease once after puberty by liver function tests and ultrasonography. Screening for fatty liver should be accurately performed in young patients with features of metabolic syndrome. Obese patients with fatty liver are at increased risk for altered glucose metabolism, thus they should undergo an oral glucose tolerance test. A nutritional and behavioral intervention aimed at achieving a permanent change of the lifestyle in patients and their parents is recommended.     

Effect of dietary seal and fish oils on triacylglycerol metabolism in rats

Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were distributed mainly in the sn-1 and 3 positions of seal oil triacylglycerol and in the sn-2 position of fish oil triacylglycerol. Seal oil or fish oil-rich fats having constant polyunsaturated/monounsaturated/saturated fatty acids and n-6/n-3 polyunsaturated fatty acid (PUFA) ratios were fed to rats for 3 wk. Control rats were fed on a fat containing linoleic acid as the sole PUFA. Seal oil more effectively lowered serum and liver triacylglycerol concentrations than fish oil. The activities of fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH) and hepatic triacylglycerol lipase (HTGL) were significantly lower in the seal oil group than in the control group, whereas the activity of HTGL was significantly lower and the hepatic peroxisomal beta-oxidation and activity of lipoprotein lipase (LPL) in adipose tissue were significantly higher in the fish oil group than in the control group. These observations suggest that the predominant hypotriacylglycerolemic effect of seal oil is caused by the suppression of fatty acid synthesis.     

Effect of ethanol administration on the in vivo kinetics of thiamine phosphorylation and dephosphorylation in different organs. I. Chronic effects

The effects of chronic ethanol administration on different steps in the metabolism of thiamine (T), thiamine mono- (TMP) and pyrophosphate (TPP) were determined in vivo in the liver, kidney, heart, skeletal muscle and small intestinal mucosa. The radioactivity of T and its phosphoesters was measured in plasma and in the selected organs under steady-state conditions and at fixed time intervals (0.25-240 hr) after an i.p. injection of Thiazole-[2-14C]-thiamine (30 micrograms: 1.25 microCi) in rats chronically (35 days) ethanol-treated (daily dose of 4.7 g kg-1 body wt by gastric gavage). Two types of controls were used: pair-fed rats treated with a sucrose solution isoenergetic with ethanol, and water-treated rats. A nutritionally adequate diet, which supplied an excess of thiamine, was given to the rats, producing a virtually steady content of thiamine compounds in the tissues. The analytical data obtained were elaborated using appropriate compartmental mathematical models, which allowed the fractional rate constants, turnover rates and turnover times to be calculated. Alterations in thiamine metabolism were modest and differed according to the organs. The most widespread modification was to facilitate the entry of T (small intestine, kidney and heart) or TMP (small intestine and kidney), while no significant change of T and TMP release was seen. Sucrose had minimal effect in both steps. Enzymatic transformations of thiamine were likewise marginally affected. A general trend toward a slower T pyrophosphorylation and a faster T phosphate dephosphorylation was observed in the small intestine, kidney, heart and liver. Skeletal muscle was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary conjugated linoleic acid alleviates nonalcoholic fatty liver disease in Zucker (fa/fa) rats

Nonalcoholic fatty liver disease (NAFLD) is the preferred term to describe the spectrum of liver damage ranging from hepatic steatosis to steatohepatitis, liver fibrosis, and cirrhosis, and it is emerging as the most common liver disease in industrialized countries. Thus, the discovery of food components that would ameliorate NAFLD is of interest. Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid, has attracted considerable attention because of its potentially beneficial biological effects both in vitro and in vivo. We tested whether dietary CLA protects Zucker (fa/fa) rats from hepatic injury. After 8 wk of feeding, hepatomegaly, hepatic triglyceride (TG) accumulation, and elevated hepatic injury markers in plasma were markedly alleviated in CLA-fed Zucker rats compared with linoleic acid-fed (control) rats. These effects were attributed in part to the enhanced hepatic activities of carnitine palmitoyltransferase, a key enzyme of fatty acid beta-oxidation, and microsomal TG transfer protein, an important factor for lipoprotein secretion due to the CLA diet. We previously reported that the severe hyperinsulinemia in control Zucker rats was attenuated in CLA-fed rats due to an enhanced level of plasma adiponectin, which improves insulin sensitivity. In the present study, the adiponectin concentration was increased and the mRNA expression of tumor necrosis factor-alpha, an inflammatory cytokine, was markedly suppressed in the liver of CLA-fed Zucker rats. We speculate that the enhanced level of liver adiponectin may prevent the development and progression of NAFLD in CLA-fed Zucker rats.