Differential regulation of hepatic gene expression by starvation versus refeeding following a high-sucrose or high-fat diet

OBJECTIVES: The objective of this work was to determine the effects of starvation versus refeeding following a high-sucrose diet (HS) or high-fat diet (HF) on fatty acid metabolism in mice. METHODS: The mice were fed an AIN-76 control diet (CD), a modified HS, or an HF. The three dietary groups were subdivided into three groups each: those fed experimental diets for 12 wk, mice starved for 48 h after 12 wk on an experimental diet, and those with the same starvation treatment but with 72 h of refeeding after starvation, respectively. RESULTS: Serum total cholesterol levels of CD and HF groups decreased and then increased under starvation and refeeding states, respectively. Refeeding HS and HF increased serum levels of low-density lipoprotein (LDL) cholesterol compared with refeeding of the CD group. Starvation significantly increased hepatic levels of total cholesterol in the HS and HF groups compared with the CD group. Hepatic acyl coenzyme A (CoA) synthetase (ACS) levels in the CD and HS groups but not the HF group increased and then decreased under starved and refed states, respectively; an opposite regulation was observed in the HF group. Levels of hepatic acetyl-CoA carboxylase (ACC) in the HS and HF groups were significantly increased by refeeding. Hepatic levels of carnitine palmitoyltransferase-I mRNA were significantly enhanced by starvation and refeeding in the HS group but decreased in CD and then increased in the HF group. CONCLUSIONS: Changes in dietary energy nutrients, fasting, and refeeding affect hepatic ACS, CPT-I, and ACC mRNA expression, and these results will serve to enhance our understanding of the molecular mechanisms underlying regulation of fatty acid metabolism.     

断乳后饲料构成对大鼠肝脏CPT-Ⅰ mRNA表达影响

目的研究断乳后饲料构成对大鼠肝脏肉碱棕榈酰转移酶-Ⅰ（CPT-Ⅰ）mRNA表达的影响.方法新生Wistar雄性大鼠24d断乳,按体重随机分为A、B、C、D 4组,分别喂饲高碳水化合物、高蛋白质、高不饱和脂肪酸和高饱和脂肪酸构成饲料3周后,基础饲料喂养2周,A组按体重随机再分为A1、A2 2组.A1组喂饲基础饲料作为对照组,A2和B、C、D 4组给予高脂饲料喂养6周,A2组作为高碳水化合物组.动态检测大鼠的体重、体脂含量、血糖及肝脏肉碱棕榈酰转移酶-Ⅰ mRNA水平.结果实验末期,C组大鼠体重、体脂含量和血糖均明显低于A2组（P〈0.05）;B组大鼠体重和体脂含量明显低于A2组（P〈0.05）,但血糖水平高于A2组;D组大鼠体重明显低于A2组（P〈0.05）,但血糖和体脂含量与A2组差异无统计学意义（P＞0.05）.动态观察表明,C组大鼠CPT-Ⅰ mRNA水平持续升高,且在实验末期明显高于其他组.结论断乳后进食高不饱和脂肪酸构成饲料可能通过持续增加CPT-Ⅰ基因表达,抑制大鼠肥胖形成.     

Vitamin A deficiency modifies lipid metabolism in rat liver

Liver fatty acid metabolism of male rats fed on a vitamin A-deficient diet for 3 months from 21 d of age was evaluated. Vitamin A restriction produced subclinical plasma and negligible liver retinol concentrations, compared with the control group receiving the same diet with 4000 IU vitamin A (8 mg retinol as retinyl palmitate)/kg diet. Vitamin A deficiency induced a hypolipidaemic effect by decreasing serum triacylglycerol, cholesterol and HDL-cholesterol levels. The decrease of liver total phospholipid was associated with low phosphatidylcholine synthesis observed by lower [14C]choline incorporation into phosphatidylcholine, compared with control. Also, liver fatty acid synthesis decreased, as was indicated by activity and mRNA expression of acetyl-CoA carboxylase (ACC), and incorporation of [14C]acetate into saponified lipids. A decrease of the PPARalpha mRNA expression was observed. Liver mitochondria of vitamin A-deficient rats showed a lower total phospholipid concentration coinciding with a decrease of the cardiolipin proportion, without changes in the other phospholipid fractions determined. The mitochondria fatty acid oxidation increased by 30 % of the control value and it was attributed to a high activity and mRNA expression of carnitine palmitoyltransferase-I (CPT-I). An increase in serum beta-hydroxybutyrate levels was observed in vitamin A-deficient rats. Vitamin A deficiency alters the mitochondria lipid composition and also enhances fatty acid oxidation by modifying the production of malonyl-CoA, the endogenous inhibitor of CPT-I, due to decreased activity of liver ACC. The incorporation of vitamin A into the diet of vitamin A-deficient rats reverted all the changes observed.     

Regulation of acetyl CoA carboxylase and carnitine palmitoyl transferase-1 in rat adipocytes

OBJECTIVE: Acetyl CoA carboxylase (ACC) is a key enzyme in energy balance. It controls the synthesis of malonyl-CoA, an allosteric inhibitor of carnitine palmitoyltransferase-1 (CPT-I). CPT-I is the gatekeeper of free fatty acid (FFA) oxidation. To test the hypothesis that both enzymes play critical roles in regulation of FFA partitioning in adipocytes, we compared enzyme mRNA expression and specific activity from fed, fasted, and diabetic rats. RESEARCH METHODS AND PROCEDURES: Direct effects of nutritional state, insulin, and FFAs on CPT-I and ACC mRNA expression were assessed in adipocytes, liver, and cultured adipose tissue explants. We also determined FFA partitioning in adipocytes from donors exposed to different nutritional conditions. RESULTS: CPT-I mRNA and activity decreased in adipocytes but increased in liver in response to fasting. ACC mRNA and activity decreased in both adipocytes and liver during fasting. These changes were not caused directly by fasting-associated changes in plasma insulin and FFA concentrations because insulin suppressed CPT-I mRNA and did not affect ACC mRNA in vitro, whereas exogenous oleate had no effect on either. Despite the decrease in adipocyte CPT-I mRNA and specific activity, CO(2) production from endogenous FFAs increased, suggesting increased FFA transport through CPT-I for beta-oxidation. DISCUSSION: Stimulation of FFA transport through CPT-I occurs in both tissues, but CPT-I mRNA and specific activity correlate with FFA transport in liver and not in adipocytes. We conclude that the mechanism responsible for increasing FFA oxidation in adipose tissue during fasting involves mainly allosteric regulation, whereas altered gene expression may play a central role in the liver.     

Azuki bean polyphenols intake during lactation upregulate AMPK in male rat offspring exposed to fetal malnutrition

ObjectiveFetal malnutrition is an early-life inducer of dyslipidemia and glucose intolerance. The aim of this study was to examine whether maternal azuki bean (Vigna angularis) polyphenol (AP) intake during lactation affects the adenosine monophosphate–activated protein kinase (AMPK) pathway and lipid metabolism in offspring exposed to fetal malnutrition.MethodsPregnant Wistar rats were divided into three groups: a control diet offered during gestation and lactation (CC), a low-protein diet during gestation and a control diet during lactation (LPC); and a low-protein diet during gestation and a 1.0% AP-containing control diet during lactation (LPAP). Male pups were randomly selected for the study; half the pups were sacrificed at 3 wk of age and the other half were fed a standard diet and sacrificed at 23 wk. Hepatic triacylglycerol levels, phosphorylation levels of AMPK and acetyl-coenzyme A carboxylase (ACC), and mRNA levels of sterol regulatory element-binding protein-1c (SREBP-1c) were evaluated.ResultsSignificant decreases in body weights and hepatic triacylglycerol levels were found in the LPAP compared with the LPC group. Plasma adiponectin levels in the LPAP group were higher than those in the LPC group. AMPK phosphorylation was upregulated in the livers and skeletal muscles in young and adult LPAP compared with LPC rats. ACC phosphorylation was upregulated in skeletal muscles of LPAP rats. SREBP-1c mRNA expression was decreased in the livers of LPAP rats.ConclusionOur results suggest that maternal AP intake during lactation upregulates AMPK phosphorylation not only in young but also in adult offspring exposed to fetal malnutrition and may lead to decreased hepatic lipid accumulation by ACC phosphorylation and downregulation of SREBP-1c expression.     

单纯性肥胖儿童血清瘦素水平与血糖及血脂变化的关系

目的 研究单纯性肥胖儿童血清瘦素水平与血糖、胰岛素抵抗及血脂异常的关系。方法 采用放射免疫分析法、酶法对42对7-10岁肥胖及健康对照儿童进行血清瘦素、胰岛素水平及血糖、血脂水平的测定。结果 肥胖及对照儿童瘦素水平分别为2．74-45．125μg/L和0．53-10．18μg/L,经对数转换后肥胖组平均水平非常显著高于体重正常组。血清瘦素水平与体重指数(BMI)、腰臀围比(WHR)及体脂百分比均呈显著正相关关系。83％的肥胖儿童有瘦素抵抗,肥胖瘦素敏感组与体重正常组的血糖、胰岛素及血脂水平均差异无显著性,而肥胖瘦素抵抗组总胆固醇、甘油三酯(TG)、低密度脂蛋白胆固醇及胰岛素水平均显著高于体重正常组,肥胖瘦素敏感与瘦素抵抗儿童年龄、性别分布及BMI、WHR的差异无显著性,但瘦素抵抗组TG显著高于瘦素敏感组,高密度脂蛋白胆固醇显著低于瘦素敏感组。结论 肥胖儿童即存在瘦素抵抗,瘦素抵抗与代谢综合征及心血管疾病的危险因素密切相关,可作为筛查高危肥胖儿童的有用指标。     

共轭亚油酸对饮食诱导肥胖大鼠脂代谢及相关基因表达的影响

目的:通过研究共轭亚油酸(CLA)对饮食诱导肥胖大鼠脂肪酸转移蛋白、酰基CoA合成酶基因表达的影响,探讨CLA抗糖尿病机制。方法:选雄性Wistar大鼠,随机分为对照组、高脂组、高脂+CLA组(每100g饲料含CLA分别为0.75、1.50、3.00g),每组动物10只,观察CLA对肥胖大鼠血清游离脂肪酸(FFA)、胰岛素、血糖水平的影响,并应用RT-PCR法检测脂肪酸转移蛋白(FATP)、酰基CoA合成酶(ACS)、过氧化物酶体增殖物活性受体γ(PPARγ)mRNA的表达水平。结果:高脂组大鼠血清FFA、胰岛素和血糖水平显著高于对照组,CLA可降低肥胖大鼠血清FFA、胰岛素、血糖水平,并且可增加肥胖大鼠脂肪组织FATP、ACS、PPARγmRNA的表达水平。结论:CLA可通过激活PPARγ上调FATP、ACS基因的表达,改善肥胖大鼠的胰岛素抵抗。     

Leptin, soluble leptin receptor, lipid profiles, and LEPR gene polymorphisms in Thai children and adolescents

OBJECTIVE: To evaluate the relationships between leptin, soluble leptin receptor, lipid profiles, and LEPR gene polymorphisms in child and adolescent Thai subjects. DESIGN: Cross-sectional study of Thai children and adolescents. SUBJECTS: 116 male and 65 female at risk for overweight/overweight child and adolescent Thai subjects, and 33 male and 62 female healthy child and adolescent Thai subjects (age: 5-19 years). MEASUREMENTS: Leptin levels, soluble leptin receptor levels, lipid profiles, LEPR gene polymorphisms. RESULTS: Significantly higher levels of cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and leptin levels were observed in at risk for overweight/overweight group. On the other hand, high-density lipoprotein cholesterol (HDL-C) and soluble leptin receptor levels were significantly lower in the same group. Serum soluble leptin receptor levels were significantly negatively correlated with leptin. The at risk for overweight/overweight subjects with the Lys656Lys homozygous wild type LEPR gene had significantly higher cholesterol and LDL-C levels than those with Lys656Asn heterozygous and Asn656Asn homozygous mutant type. In contrast, subjects with Lys656Lys homozygous wild type had significantly lower leptin levels than those with Lys656Asn heterozygous and Asn656Asn homozygous mutant type. There was a statistically significant association between body mass index (BMI) and hyperleptinemia (odds ratio; OR = 2.49, p = 0.000) and females had more increased risk of hyperleptinemia than males (OR = 15.74, p = 0.004) in adolescent Thai subjects. CONCLUSION: The present study is the first report of Lys656Asn polymorphism of the LEPR gene associated with cholesterol, LDL-C, and leptin levels in Thai children and adolescents. Serum leptin levels were significantly higher in the at risk for overweight/overweight. In contrast, there were significantly lower soluble leptin receptor levels in the same group. In addition, there was a statistically significant association between BMI, sex, and hyperleptinemia in adolescent Thai subjects.     

Antiobesity effects of kimchi added with Jeju citrus concentrate on high-fat diet-induced obese mice

Citrus fruits contain an abundance of nutrients, including vitamins C and B₆ and hesperidin, which attribute to its beneficial health effects. Previously, kimchi with Jeju citrus concentrate (CK) elicited anti-obesity effects in 3T3-L1 adipocytes. Here, we aimed to investigate whether CK exhibits anti-obesity effects by reducing serum and hepatic lipid concentrations and anti-obesity-associated gene expression in high-fat diet (HFD)-induced obese C57BL/6N mice. Low-dose CK (LDCK, 50 mg/kg) and high-dose CK (HDCK, 200 mg/kg) were orally administered 3 times per week over 8 weeks with HFD diet. Body weight gain, food efficiency ratio, and tissue weight were measured. Serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, fasting glucose, fasting insulin, homeostatic model assessment-insulin resistance, leptin, and adiponectin concentrations were also assessed. The effect of CK on the lipid profile and lipid accumulation was analyzed. Body and white adipose tissue masses were significantly lower in the LDCK and HDCK groups than in the HFD group. Orally administered CK significantly decreased serum lipid, fasting glucose, fasting insulin, homeostatic model assessment-insulin resistance, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase levels. Hepatic lipid content also decreased in the LDCK and HDCK groups. Serum leptin concentrations decreased, whereas serum adiponectin concentrations increased, confirming the anti-obesity effects of LDCK and HDCK. The decrease of hepatic vacuoles and stained lipid droplets indicated inhibition of lipid accumulation. These results support the hypothesis that CK exhibits anti-obesity effects in vivo by reducing lipid accumulation and by regulating anti-obesity-related genes.     

Tissue-specific regulation of acetyl-CoA carboxylase gene expression by dietary soya protein isolate in rats

We have recently reported that intake of soya protein isolate (SPI) inhibited the DNA-binding activities of hepatic thyroid hormone receptor (TR). The genes for acetyl-CoA carboxylase (ACC), a rate-limiting enzyme in fatty acid synthesis, contain the thyroid hormone response element in their promoters and are regulated by TR. The present study has examined the effect of long-term feeding of SPI and soya isoflavones (ISF) on the gene expression and protein phosphorylation of different ACC isoforms in different tissues and plasma triacylglycerol (TAG) levels in rats. Sprague-Dawley female rats were fed diets containing 20 % casein or alcohol-washed SPI with or without supplemental ISF for 70, 190 and 310 d. SPI intake significantly reduced plasma TAG concentrations compared with casein, whereas supplemental ISF had no effect. Hepatic ACCalpha and ACCbeta mRNA abundance and protein content were markedly lower in the rats fed SPI than in those fed casein. The protein contents of ACCalpha in the kidney and ACCbeta, the predominant isoform in the heart and kidney, were unchanged by dietary SPI. The ratios of phospho-ACCalpha/ACCalpha and phospho-ACCbeta/ACCbeta were not different among dietary groups in all tissues measured. The present study demonstrates that ingestion of SPI decreases plasma TAG level and down-regulates ACCalpha and ACCbeta gene expression in the liver but not in the heart and kidney. The results indicate that the effect of SPI is tissue-specific and that alteration of ACC gene expression rather than phosphorylation status may play a major role in the regulation of ACC activities by soya proteins.     

Effects of biotin on pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects

BACKGROUND: Several studies have shown that biotin affects glucose homeostasis. Serum biotin concentrations are lower in subjects with type 2 diabetes than in control subjects. Lymphocyte propionyl-CoA carboxylase (PCC; EC 6.4.1.3) activity has proved to be a sensitive indicator of biotin status that is more accurate than is serum biotin concentration. OBJECTIVE: We studied the activity of PCC, pyruvate carboxylase (PC; EC 6.4.1.1), and acetyl-CoA carboxylase (ACC; EC 6.4.1.2) in type 2 diabetic and nondiabetic subjects. The effect of biotin administration (6.14 micro mol/d) on the activity of these enzymes and on several plasma metabolites was also studied. DESIGN: We compared the activities of carboxylases in circulating lymphocytes from patients with type 2 diabetes (n = 24) with those in circulating lymphocytes from nondiabetic subjects (n = 30). We also assessed the effect of biotin administration for 14 and 28 d on the activity of these enzymes and on the concentrations of several metabolites (type 2 diabetic patients, n = 10; nondiabetic subjects, n = 7). RESULTS: No significant differences in lymphocyte carboxylase activities were found between the type 2 diabetic patients and the nondiabetic subjects. Biotin administration increased the activity of PCC, PC, and ACC in all the subjects. No significant change in glucose, insulin, triacylglycerol, cholesterol, or lactate concentration was observed with the treatment in either the diabetic or the nondiabetic subjects. CONCLUSIONS: The activity of carboxylases does not differ significantly between type 2 diabetic and nondiabetic subjects. Pharmacologic doses of biotin increase lymphocyte PCC, PC, and ACC activities.     

中链甘油三酯饮食对神经肽Y及瘦素的作用研究

目的观察中链甘油三酯(MCT)对血清和下丘脑瘦素、神经肽Y(NPY)浓度,下丘脑长型瘦素受体(Ob-Rb)、mRNA表达的影响。方法20只Wistar雄性大鼠,用含30%MCT或长链甘油三酯(LCT)的饲料喂养8周,用ELISA法测定血清和下丘脑瘦素的水平,用放射免疫法检测外周血和下丘脑NPY的浓度,用real-time RT-PCR技术测定下丘脑NPY、瘦素受体(Ob-Rb)基因表达水平的差异。结果MCT组大鼠体重增长量和体脂含量均小于LCT组(P<0.01),MCT组瘦素脑/血比明显高于LCT组,MCT组大鼠下丘脑ob-Rb mRNA表达水平明显高于LCT组(P<0.01),下丘脑及血清NPY浓度明显低于LCT组(P<0.01)。结论MCT通过促进Ob-Rb基因表达,抑制NPY合成和分泌。     

Different dietary fats influence serum and tissue lipids and anti-cardiolipin antibody levels in autoimmune-prone NZB/W F1 mice

To investigate the influence of different dietary fats on lipids and anti-cardiolipin antibody levels, autoimmune NZB/W F1 mice were fed on diets containing 200 g dietary fat as palm oil, lard-soyabean oil (1:1, w/w), soyabean oil, rapeseed oil or fish oil/kg. In addition, each dietary fat group was divided into an early-feeding group with feeding from 2 months of age, and a late-feeding group with feeding from 5 months of age. Serum levels of triacylglycerol, phospholipid, cholesterol and anti-cardiolipin antibody were measured at regular intervals, and mice were killed at the age of 7 months for analysis of hepatic lipid and fatty acids. The results showed that hepatic triacylglycerol and cholesterol contents were lower in mice fed on fish oil than in those fed on palm oil. In contrast, hepatic phospholipid content was higher in mice of the fish oil group than in those of the other four dietary fat groups. Composition profiles for both hepatic and renal oleic acid (18: 1n-9), linoleic acid (18: 2n-6) and eicosapentaenoic acid (20: 5n-3) were similar to those of the dietary fats in mice of both early-feeding and late-feeding groups. Fish oil intake decreased arachidonic acid (20: 4n-6) concentration in kidney tissue but not in liver tissue. Serum triacylglycerol, cholesterol and phospholipid levels were lower in mice fed on fish oil than in those fed on palm oil. Immunoglobulin (Ig) M anti-cardiolipin antibody was lower for the fish oil group than for the other groups. The IgG anti-cardiolipin antibody level was significantly lower in mice fed on fish oil compared with that of the palm oil group only in the early-feeding group. There was a positive correlation between serum IgM anti-cardiolipin antibody and phospholipid levels (early-feeding group r 0.902, P < 0.05; late-feeding group r 0.894, P < 0.05). These findings suggest dietary fish oil may affect both lipid levels and anti-cardiolipin antibody, contributing to alleviation of the autoimmune process in autoimmune-prone NZB x NZW F1 mice.     

BMI is the main determinant of the circulating leptin in women after vertical banded gastroplasty

OBJECTIVE: To assess the main determinant of serum leptin concentration changes in morbidly obese patients treated by banded vertical gastroplasty. RESEARCH METHODS AND PROCEDURES: Serum leptin and insulin concentrations, insulin resistance, BMI, body weight, and body fat mass in 18 obese women and 8 obese men treated by vertical banded gastroplasty were studied. Lean women and men subjects were used as controls. RESULTS: Before surgery, serum leptin and insulin concentrations and insulin resistance index were significantly higher in morbidly obese patients than in control subjects. BMI, body fat mass, and serum triacylglycerol concentrations were also significantly higher in obese than in lean subjects. All of these parameters gradually decreased during 50 weeks after surgery. Univariate regression analysis displayed significant correlations between the following: serum leptin concentration and BMI (and body fat mass), serum leptin concentration and serum insulin concentration, and serum leptin concentration and insulin resistance index. Multivariate regression analysis indicated that only BMI was independently correlated with the decrease in serum leptin concentration. DISCUSSION: Obtained data suggest the following: 1) vertical banded gastroplasty causes reduction of body weight, serum leptin and insulin concentration, insulin resistance, and serum triacylglycerol concentration; and 2) BMI is the main determinant of the circulating leptin concentration in morbidly obese women after anti-obesity surgery.     

Gene expressions of leptin, insulin receptors and lipogenic enzymes are coordinately regulated by insulin and dietary fat in rats

Regulation of the gene expressions of leptin, insulin receptors and lipogenic enzymes was investigated after refeeding a fat-free diet or a 10 g/100 g corn oil diet to food-deprived rats. Plasma glucose and insulin concentrations began to increase 30 min after the feeding and further increased up until 8 h. In these rats, the expression of leptin mRNA in adipose tissue began to increase significantly only 30 min after feeding, and reached a maximum at 8-16 h. However, plasma leptin levels did not increase until 4 h after refeeding, then markedly increased and reached the maximal level after 8 h. The expression of leptin mRNA and plasma leptin concentrations generally were greater in rats fed the corn oil diet compared to those fed the fat-free diet. Insulin receptor mRNA concentrations in the liver and adipose tissue began to decrease 30 min after the refeeding, in contrast to the plasma insulin increase, and continued to decrease until 8 h. The expression of acetyl-CoA carboxylase and fatty acid synthase mRNA began to increase 4-8 h after feeding and reached maximal levels at 16-24 h. Leptin treatment suppressed the expression of lipogenic enzyme mRNA in rats fed the fat-free diet but not in corn oil-fed rats, in which the expression was suppressed by polyunsaturated fatty acids and leptin expression was higher. Thus, we suggest that the glucose and insulin-dependent expressions of leptin, insulin receptors and lipogenic enzymes are coordinately and/or mutually regulated by dietary manipulation.     

Adzuki resistant starch lowered serum cholesterol and hepatic 3-hydroxy-3-methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol 7alpha-hydroxylase mRNA levels in rats fed a cholesterol diet

We examined the effects of adzuki bean resistant starch on serum cholesterol and hepatic mRNA in rats fed a cholesterol diet. The mRNA coded for key regulatory proteins of cholesterol metabolism. The control rats were fed 15 % cornstarch (basal diet, BD). The experimental rats were fed BD plus a 0.5 % cholesterol diet (CD), or a 15 % adzuki resistant starch plus 0.5 % cholesterol diet (ACD) for 4 weeks. The serum total cholesterol and VLDL + intermediate density lipoprotein + LDL-cholesterol levels in the ACD group were significantly lower than those in the CD group throughout the feeding period. The total hepatic cholesterol concentrations in the CD and ACD groups were not significantly different. The faecal total bile acid concentration in the ACD group was significantly higher than that in the BD and CD groups. Total SCFA and acetic acid concentrations in the ACD group were significantly higher than those in the CD group but there were no significant differences in the concentrations between the ACD and BD groups. The hepatic LDL-receptor mRNA and cholesterol 7alpha-hydroxylase mRNA levels in the ACD group were significantly higher than those in the CD group and the hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase mRNA level in the ACD group was significantly lower than in the CD group. The results suggest that adzuki resistant starch has a serum cholesterol-lowering function via enhancement of the hepatic LDL-receptor mRNA and cholesterol 7alpha-hydroxylase mRNA levels and faecal bile acid excretion, and a decrease in the hepatic HMG-CoA reductase mRNA level, when it is added to a cholesterol diet.     

花色苷通过腺苷一磷酸激活蛋白激酶减少肝脏HepG2细胞的脂肪积聚

目的探讨花色苷单体矢车菊素-3-葡萄糖苷(Cy-3-g)对HepG2细胞脂肪含量的影响以及可能机制。方法HepG2细胞分别用1、10、100μmol/LCy-3-g处理1h,设置对照,检测腺苷一磷酸激活蛋白激酶(AMPK)及其磷酸化水平、肉碱脂酰转移酶-I(CPT-I)、乙酰辅酶A羧化酶(ACC)磷酸化水平、AMPK活性、甘油三酯含量以及脂肪酸氧化水平。结果与对照组相比,显著上调CPT-I蛋白的表达水平,显著增强AMPK的活性,显著促进AMPK蛋白磷酸化,但对AMPK蛋白表达水平无影响,显著减少HepG2细胞内的甘油三酯含量,10、100μmol/LCy-3-g能显著促进ACC的磷酸化,100μmol/LCy-3-g能显著促进HepG2细胞脂肪酸氧化。结论花色苷Cy-3-g可以减少HepG2细胞脂肪积聚;其机制可能与调节HepG2细胞AMPK-ACC-CPT-I信号通路,促进脂肪酸氧化有关。     

Dietary diacylglycerol induces the regression of atherosclerosis in rabbits

Recent studies of the relation between serum triacylglycerol concentration and the risk for coronary artery disease suggest that inefficient clearance of postprandial triacylglycerols promotes atherogenesis. We recently demonstrated that dietary diacylglycerol (DAG), rich in the 1,3-species, suppresses the postprandial increase in serum triacylglycerol levels compared with dietary triacylglycerol (TAG). Here, we investigated the effects of dietary DAG on atherosclerosis in rabbits with cholesterol-induced atherosclerosis. New Zealand White rabbits (n = 20) were fed a diet containing 3% lard and 1.3% cholesterol for 50 d to induce atherosclerotic lesions. Thereafter, the rabbits were assigned to 2 groups and fed 90 g/d nonpurified diet and orally administered 5 g DAG or TAG for an additional 34 d. Reference rabbits (n = 5) were fed only the nonpurified diet throughout the 84-d study. The area of atherosclerotic lesions and aortic lipid concentrations were significantly lower in DAG-fed rabbits compared with TAG-fed rabbits. The VLDL receptor and macrophage antigen-1 mRNA expression levels were significantly lower in DAG-fed rabbits than in TAG-fed rabbits. In the liver of DAG-fed rabbits, the triacylglycerol concentration was lower and the carnitine palmitoyltransferase activity higher than in TAG-fed rabbits. Stimulation of hepatic lipid catabolism might be related to the reduced lipid accumulation in the liver and aorta by reducing the release of triacylglycerol into the circulation. Thus, long-term consumption of DAG, which reduces postprandial lipemia, might be useful for the regression of atherosclerosis by stimulating hepatic lipid catabolism and thereby modulating monocyte/macrophage migration and aortic lipid accumulation.     

Dietary grape seed tannins affect lipoproteins, lipoprotein lipases and tissue lipids in rats fed hypercholesterolemic diets

The effects of monomeric and polymeric grape seed tannins on rat plasma lipoproteins, lipoprotein lipase, hepatic lipase and aortic and hepatic lipid concentration were studied. Male Sprague-Dawley rats received either a normal diet (with no added cholesterol and no tannins), a control diet (hypercholesterolemic diet) or hypercholesterolemic diets supplemented with 2% tannin monomers or 2% polymers 3 or 9 wk. Plasma total cholesterol, triacylglycerol, LDL cholesterol and VLDL concentrations were significantly higher and the HDL cholesterol concentration lower in controls and in rats fed the diet supplemented with monomers compared with rats fed polymeric tannins at both time points. Lipoprotein lipase and hepatic lipase activities were significantly higher in control and in monomer-fed groups than in the polymer-fed group. Hepatic and aortic cholesterol and triacylglycerol concentrations were significantly higher in control rats and those fed monomers than in the polymer-fed group. Moreover, plasma HDL cholesterol and hepatic lipase activity were closely associated with low aortic cholesterol and triacylglycerol in rats fed polymeric tannins. These rats also exhibited greater fecal excretion of cholesterol and especially bile acids than the control or monomer-fed groups. Thus dietary grape seed tannins have a pronounced anti-hypercholesterolemic effect by enhancing reverse cholesterol transport and also by reducing intestinal cholesterol absorption and increasing bile acid excretion.     

Dietary lipoic acid-dependent changes in the activity and mRNA levels of hepatic lipogenic enzymes in rats

Effects of dietary alpha-lipoic acid on hepatic and serum lipid concentrations and the activity and mRNA levels of lipogenic enzymes were examined in rats. Rats were fed experimental diets containing varying amounts of lipoic acid (0, 1, 2.5, 5 g/kg) for 21 d. Lipoic acid profoundly decreased serum and liver concentrations of TAG, and also lowered serum concentrations of phospholipid and NEFA, and the concentration of cholesterol in the liver. A hypoglycaemic effect of this compound was also observed. Lipoic acid dose-dependently decreased the activity and mRNA levels of fatty acid synthase, ATP-citrate lyase, glucose 6-phosphate dehydrogenase, malic enzyme and pyruvate kinase in the liver despite that reductions were considerably attenuated in the NADPH-producing enzymes. This compound also dose-dependently lowered the mRNA levels of spot 14, adiponutrin, stearoyl-CoA desaturase 1, and Delta5- and Delta6-desaturases. In addition, lipoic acid dose-dependently lowered serum concentrations of insulin and leptin, but increased those of adiponectin. Lipoic acid appeared to reduce hepatic lipogenesis and hence decreases serum and liver lipid levels. Alterations in serum concentrations of insulin and (or) adiponectin may trigger this consequence.