番茄红素对高脂血症模型大鼠肝脏保护作用研究

目的研究番茄红素对高脂血症大鼠肝脏的保护作用。方法 64只SD成年雄性大鼠按体重和血清总胆固醇(TC)随机分为对照组、模型组、氟伐他汀钠10mg/(kg bw d)、番茄红素4.4、11、22、44、110 mg/(kg bw d)共8个剂量组;实验(3w)期间,对照组饲基础饲料,其余饲高脂饲料;第2w起,对照组和模型组以溶剂1%CMC-Na灌胃,其余各组按确定剂量(1%CMC-Na为溶剂,1 ml/d)灌胃,历时2w。实验结束,检测肝脏总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、超氧化物歧化酶(SOD)、丙二醛(MDA)、脂蛋白脂酶(LPL)、肝脂酶(HL)、血管内皮生长因子(VEGF);光镜下观察肝脏病理变化并计算炎症活动度。以番茄红素各剂量组肝脏各项指标与模型组均值差的绝对数进行曲线拟合分析。结果与模型组相比,各干预组肝脏TC、TG、LDL-C、MDA和VEGF水平均有不同程度降低,SOD、LPL、HL活性均有不同程度增强;肝脏脂变和炎症现象均有不同程度减轻。番茄红素44mg/(kgbw d)组大鼠肝脏TC、TG、LDL-C、SOD、LPL、HL、MDA和VEGF水平分别为24.75±3.03、13.67±1.26、22.21±2.83mg/g、156.56±8.61、0.53±0.06、0.50±0.10 U/mg prot、14.87±1.15 nmol/mg prot和199.12±33.92 pg/mg prot。拟合得到9个曲线方程。结论番茄红素可降低高脂血症大鼠肝脏脂质,调节肝脏脂质代谢酶的活性,提高抗氧化能力减缓肝脏的脂质过氧化,影响VEGF的生成,避免炎症反应扩大而保护肝脏实质细胞和肝脏血管;采用拟合曲线方程在4.4～110 mg/(kg bw d)剂量范围,可初步了解不同剂量的番茄红素对高脂血症大鼠肝脏各指标变量的影响。     

Metabolic effects of dietary manganese supplementation in ob/ob mice

When fed a manganese-sufficient (20 ppm) diet, obese (ob/ob) mice have reduced levels of Mn in liver and brown adipose tissue (BAT), and depressed activities of succinate dehydrogenase (SDH) and manganese-containing superoxide dismutase (MnSOD) in BAT, compared to lean mice. Dietary Mn supplementation (200 ppm Mn) increased the Mn concentration in BAT in lean and obese mice and the Mn content of liver in the ob/ob mouse. Mn supplementation also led to an increase in the specific activities of SDH and MnSOD in BAT of lean and obese mice. In the obese mouse, these changes were paralleled by changes in the histological appearance of the tissue. The results indicate that the metabolism of Mn is altered in the liver and BAT of ob/ob mice, and that these alterations are responsive to dietary Mn supplementation.     

Carcass and liver composition following acute oxytetracycline treatment of ob/ob mice

Fully mature (24-week old) C57BL/6J ob/ob mice and their lean littermates received daily oxytetracycline injections (50 or 100 mg/kg) during a 10 day period. The effects of the drug on the glucose, IRI, corticosterone levels, and on hepatic and body composition of ad libitum fed obese mice were compared with those of food-restricted and ad libitum fed lean and obese control animals. When compared with food-restricted obese mice, drug treatment led to substantial reductions of serum glucose, serum IRI, carcass fat, and hepatic lipid content, while it increased lean body mass and liver glycogen concentration. Similarly, oxytetracycline decreased body weight, and serum glucose in lean mice, but the drug had no substantial effect on circulating IRI levels or on the lipid content of carcass. A significant increase in hepatic lipid was observed in drug-treated lean mice. No effects of the drug on basal corticosterone levels were noted in either phenotype. These data support previous findings showing the effectiveness of oxytetracycline to reverse many of the metabolic abnormalities of ob/ob mice. In addition, the present results suggest that the drug acts by independently altering abnormal metabolism in many target organs, including pancreas, adipose tissue, liver, and muscle, rather than by merely reducing circulating insulin levels or by generally increasing insulin sensitivity.     

Fish Oil Enriched n-3 Polyunsaturated Fatty Acids Improve Ketogenic Low-Carbohydrate/High-Fat Diet-Caused Dyslipidemia,Excessive Fat Accumulation,and Weight Control in Rats

Low-carbohydrate and high-fat diets have been used for body weight (BW) control, but their adverse effects on lipid profiles have raised concern. Fish oil (FO), rich in omega-3 polyunsaturated fatty acids, has profound effects on lipid metabolism. We hypothesized that FO supplementation might improve the lipid metabolic disturbance elicited by low-carbohydrate and high-fat diets. Male SD rats were randomized into normal control diet (NC), high-fat diet (HF), and low-carbohydrate/high-fat diet (LC) groups in experiment 1, and NC, LC, LC + 5% FO (5CF), and LC + 10% FO diet (10CF) groups in experiment 2. The experimental duration was 11 weeks. In the LC group, a ketotic state was induced, and food intake was decreased; however, it did not result in BW loss compared to either the HF or NC groups. In the 5CF group, rats lost significant BW. Dyslipidemia, perirenal and epididymal fat accumulation, hepatic steatosis, and increases in triglyceride and plasma leptin levels were observed in the LC group but were attenuated by FO supplementation. These findings suggest that a ketogenic low-carbohydrate/high-fat diet with no favorable effect on body weight causes visceral and liver lipid accumulation. FO supplementation not only aids in body weight control but also improves lipid metabolism in low-carbohydrate/high-fat diet-fed rats.     

Reduced brain norepinephrine metabolism in obese (ob/ob) mice is not normalized by tyrosine supplementation

Five-week-old female lean and obese (ob/ob) mice were fed a 20% protein diet (1.1% tyrosine) or a 20% protein diet supplemented with tyrosine (4% tyrosine). On d 4 of supplementation, brain norepinephrine (NE) synthesis rate and brain efflux of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), a major metabolite of NE in mouse brain, were measured after administration of the monoamine oxidase inhibitor pargyline. Control obese mice had a lower rate of NE synthesis and a lower MHPG efflux than lean controls. Tyrosine supplementation elevated brain tyrosine concentration twofold, but had no effect on NE synthesis rate or MHPG efflux in either group. Likewise, tyrosine supplementation for up to 1 mo had no effect on food intake, oxygen consumption or body weight in obese mice and only a transient effect in lean mice, in which oxygen consumption was higher on d 2 and 3 and food intake was higher on d 3 and 4 compared with nonsupplemented lean mice. We conclude that tyrosine availability is not a limiting factor in the reduced brain noradrenergic activity of obese mice.     

Flaxseed lignan attenuates high-fat diet-induced fat accumulation and induces adiponectin expression in mice

Flaxseed lignan secoisolariciresinol diglucoside (SDG) has been reported to prevent and alleviate lifestyle-related diseases including diabetes and hypercholesterolaemic atherosclerosis. This study assesses the effect of SDG on the development of diet-induced obesity in mice and the effect of the SDG metabolite enterodiol (END) on adipogenesis in 3T3-L1 adipocytes. We compared body weight, visceral fat weight, liver fat content, serum parameters, mRNA levels of lipid metabolism-related enzymes and adiponectin in mice fed either a low-fat diet (5 % TAG), high-fat diet (30 % TAG) or high-fat diet containing 0.5 and 1.0 % (w/w) SDG for 4 weeks. Administration of SDG to mice significantly reduced high-fat diet-induced visceral and liver fat accumulation, hyperlipaemia, hypercholesterolaemia, hyperinsulinaemia and hyperleptinaemia. SDG also suppressed sterol regulatory element binding protein 1c mRNA level in the liver and induced increases in the adiponectin mRNA level in the white adipose tissue and carnitine palmitoyltransferase I mRNA level in the skeletal muscle. Differentiated 3T3-L1 adipocytes were treated with 0, 5, 10 and 20 mumol/l END and then assayed for mRNA expression of adipogenesis-related genes and DNA binding activity of PPARgamma to the PPAR response element consensus sequence. END induced adipogenesis-related gene mRNA expression including adiponectin, leptin, glucose transporter 4 and PPARgamma, and induced PPARgamma DNA binding activity in 3T3-L1 adipocytes. In conclusion, SDG induced adiponectin mRNA expression and showed beneficial effects on lipid metabolism in diet-induced obesity in mice. Flaxseed lignans are suggested to regulate adipogenesis-related gene expressions through an increase in PPARgamma DNA binding activity.     

Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction

We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40?%, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35?% (P?相似文献   

Reduction of body weight by dietary garlic is associated with an increase in uncoupling protein mRNA expression and activation of AMP-activated protein kinase in diet-induced obese mice

This study investigated the antiobesity effect of garlic in diet-induced obese mice. Male C57BL/6J mice were fed a high-fat diet (45% fat) for 8 wk to induce obesity. Subsequently, they were fed a high-fat control diet, high-fat diets supplemented with 2%, or 5% garlic (wt:wt) for another 7 wk. Dietary garlic reduced body weight and the mass of various white adipose tissue deposits and also ameliorated the high-fat diet-induced abnormal plasma and liver lipid profiles. Garlic supplementation significantly decreased the mRNA levels of adipogenic genes in white adipose tissues (WAT). However, consumption of garlic increased the expression of mRNA for uncoupling proteins in brown adipose tissue (BAT), liver, WAT, and skeletal muscle. Mice treated with garlic maintained a significantly higher body temperature than untreated mice during a 6-h, 4°C cold challenge and, notably, AMP-activated protein kinase (AMPK) activity was stimulated in BAT, liver, WAT, and skeletal muscle. These results suggest that the antiobesity effects of garlic were at least partially mediated via activation of AMPK, increased thermogenesis, and decreased expression of multiple genes involved in adipogenesis.     

Cordyceps militaris alleviates non-alcoholic fatty liver disease in ob/ob mice

BACKGROUND/OBJECTIVES

Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model.

MATERIALS/METHODS

Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined.

RESULTS

Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels.

CONCLUSIONS

These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.     

Phosphatidylethanolamine-N-methyltransferase activity and dietary choline regulate liver-plasma lipid flux and essential fatty acid metabolism in mice

Phosphatidylethanolamine-N-methyltransferase (PEMT) catalyzes the methylation of phosphatidylethanolamine to form phosphatidylcholine (PC) and represents one of the two major pathways for PC biosynthesis. Mice with a homozygous disruption of the PEMT gene are dependent on the 1,2-diacylglycerol cholinephosphotransferase (CDP-choline) pathway for the synthesis of PC and develop severe liver steatosis when fed a diet deficient in choline. The present study used quantitative lipid metabolite profiling to characterize lipid metabolism in PEMT-deficient mice fed diets containing varying concentrations of choline. Choline supplementation restored liver, but not plasma PC concentrations of PEMT-deficient mice to levels commensurate with control mice. Choline supplementation also restored plasma triglyceride concentrations to normal levels, but did not restore plasma cholesterol ester concentrations in the PEMT-deficient mice to those equal to control mice. PEMT-deficient mice also had substantially diminished concentrations of docosahexaenoic acid [22:6(n-3)] and arachidonic acid [20:4(n-6)] in plasma, independent of choline status. Thus, choline supplementation rescued some but not all of the phenotypes induced by the knockout. These findings indicate that PEMT activity functions beyond its recognized role as a compensatory pathway for PC biosynthesis and that, in contrast, PEMT activity is involved in many physiologic processes including the flux of lipid between liver and plasma and the delivery of essential fatty acids to blood and peripheral tissues via the liver-derived lipoproteins.     

Matcha Green Tea Alleviates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice by Regulating Lipid Metabolism and Inflammatory Responses

Lately, matcha green tea has gained popularity as a beverage and food additive. It has proved to be effective in preventing obesity and related metabolic syndromes. However, the underlying mechanisms of its control effects against non-alcoholic fatty liver disease (NAFLD) are complicated and remain elusive. In the present study, we performed an in vivo experiment using male C57BL/6 mice fed with a high-fat diet and simultaneously treated with matcha for six weeks. Serum biochemical parameters, histological changes, lipid accumulation, inflammatory cytokines, and relevant indicators were examined. Dietary supplementation of matcha effectively prevented excessive accumulation of visceral and hepatic lipid, elevated blood glucose, dyslipidemia, abnormal liver function, and steatosis hepatitis. RNA sequencing analyses of differentially expressed genes in liver samples indicated that matcha treatment decreased the activity of lipid droplet-associated proteins and increased the activity of cytochrome P450 enzymes, suggesting improved metabolic capacity and liver function. The current study provided evidence for new dietary strategies based on matcha supplementation to ameliorate lipotoxicity-induced obesity and NALFD.     

Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3T3-L1 cells and C57BL/6J and ob/ob mice

Inflammation plays a major role in the development of chronic diseases such as cardiovascular disease and Type 2 diabetes. Further, it was demonstrated that obese animals and humans have significantly higher levels of circulating proinflammatory cytokines, such as interleukin-6 (IL-6). The aim of this study was to determine whether adipose tissue could be a major source of circulating IL-6 in leptin-deficient obese (ob/ob) mice by comparing the expression of IL-6 in different tissues of ob/ob mice. Our secondary goal was to determine whether preadipocytes are the source of adipose tissue IL-6. The ob/ob mice had higher levels of plasma IL-6 (P < 0.05) and adipose tissue IL-6 mRNA (P < 0.05) compared with lean mice. Interestingly, IL-6 mRNA levels of liver and spleen were not different between ob/ob and lean mice, whereas adipose tissue IL-6 mRNA levels were higher in the ob/ob mice compared with lean mice (P < 0.05). In addition, we showed that IL-6 secretion from the adipose tissue stromal vascular fraction cells was higher than that from fully differentiated adipocytes (P < 0.001). We further demonstrated that 3T3-L1 preadipocytes had significantly higher levels of lipopolysaccharide (LPS)-stimulated IL-6 mRNA and IL-6 secretion than differentiated 3T3-L1 adipocytes. Taken together, these data suggest that adipose tissue and preadipocytes from the adipose tissue stromal vascular fraction may contribute significantly to the increased plasma IL-6 levels in ob/ob mice.     

Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood

Nicotinamide riboside, an NAD⁺ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD⁺ decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.     

饲料中丙酸和丁酸对肥胖小鼠脂肪代谢的影响

目的 探讨外源性短链脂肪酸对高脂诱导的肥胖小鼠脂肪代谢的影响。方法 将40只3~4周龄C57BL/6J雄性小鼠分成4组,分别给予正常饲料、高脂饲料以及分别添加丙酸和丁酸的高脂饲料喂养4个月。喂养过程结束后,心脏采血,取性腺周围脂肪、肩胛骨下脂肪和肝脏。检测血浆甘油三酯(TG)、总胆固醇(TCH)等浓度,观察脂肪和肝脏组织细胞形态变化,同时检测甘油三酯脂肪酶(atgl)、激素敏感脂肪酶(hsl)、二酯酰甘油酰基转移酶2(dgat2)、肉碱脂酰转移酶(cpt)及解偶联蛋白1(ucp1)等基因mRNA表达水平。结果 与正常饲料喂养组相比,高脂饲料组小鼠体重、血浆TG和TCH水平、肝脏脂肪聚集均显著增加(P<0.05);而高脂饲料中添加丙酸和丁酸则抑制了小鼠体重的增加和肝脏脂滴聚集,同时降低了血浆TG和TCH水平(P<0.05)。脂肪代谢相关基因表达检测显示,与正常饲料组小鼠相比,高脂饲料组小鼠性腺周围脂肪组织和肝脏中atgl、hsl、cpt1c基因mRNA的表达量均显著性降低,而dgat2基因mRNA的表达量明显升高(P<0.05);而高脂饲料中添加丙酸和丁酸提升了性腺周围脂肪组织和肝脏中agtl、hsl、cpt1c基因mRNA的表达,而抑制了dgat2的表达(P<0.05)。肩胛骨下脂肪中上述基因的表达几乎未受到饲料丙酸和丁酸添加的影响(P>0.05)。结论 丙酸和丁酸可能通过促进脂肪分解和氧化对高脂饲料诱导肥胖小鼠的体重增加发挥抑制作用。     

Digestion rate of dietary starch affects the systemic circulation of lipid profiles and lipid metabolism-related gene expression in weaned pigs

The present study was conducted to investigate the effect of digestion rate of dietary starch on postprandial systemic circulating glucose, insulin and lipid profiles, and the activity and gene expression of lipid metabolism-related enzymes in weaned pigs. A total of twenty-four weaned pigs, surgically fitted with a catheter in the jugular vein, were randomly assigned to three dietary treatment groups, representing the high digestion rate starch (HDRS) group, the moderate-digestion rate starch (MDRS) group and the low-digestion rate starch (LDRS) group. The amylopectin:amylose ratios in the diets of each group were 27·6:1, 27·6:8·5 and 1:27·6, respectively. The serum concentrations of glucose, TAG, total cholesterol, LDL-cholesterol and HDL-cholesterol in the HDRS group were increased to the peak point at postprandial 1·5, 2·5, 2·5, 1·5 and 1·5?h, those in the MDRS group were at postprandial 2·5, 3·5, 3·5, 3·5 and 3·5?h and those in the LDRS group were at postprandial 2·5, 3·5, 3·5, 1·5 and 3·5?h, respectively. The serum concentration of insulin in the HDRS group was higher (P?相似文献   

Effects of dietary genistein on hepatic lipid metabolism and mitochondrial function in mice fed high-fat diets

OBJECTIVE: Genistein has been suggested to prevent insulin resistance and its related diseases. We investigated the effects of dietary genistein at different levels on hepatic lipid levels and mitochondrial functions in mice fed high-fat diets. METHODS: C57BL/6J mice were randomly divided into four groups and fed a high-fat diet containing genistein at levels of 0%, 0.1%, 0.2%, and 0.4% (HF, HF + 0.1G, HF + 0.2G, and HF + 0.4G) for 12 wk. We measured lipid levels in the blood and liver. We also observed messenger RNA (mRNA) expression of genes encoding proteins related to lipid and energy metabolism and antioxidant defense system and mitochondrial enzyme activities in the liver. RESULTS: The induction of fatty liver by HF was substantially decreased in the HF + 0.2G and HF + 0.4G groups. Peroxisome proliferator-activated receptorgamma coactivator mRNA was increased by HF + 0.4G. Although genistein did not affect peroxisomal acyl-CoA oxidase mRNA expression, it increased medium-chain acyl-CoA dehydrogenase mRNA expression in a dose-dependent manner and HF + 0.2G increased uncoupling protein-2 mRNA expression two-fold relative to HF mice. Genistein decreased malondialdehyde levels and increased glutathione levels in liver homogenates, regardless of dose. The HF + 0.1G diet increased mitochondrial glutathione peroxidase activity and mitochondrial succinate dehydrogenase activity. CONCLUSIONS: Although genistein at higher levels decreased hepatic fat accumulation possibly by increasing fatty acid oxidation and uncoupling protein, low-dose genistein increased mitochondrial enzyme activities in mice with fatty liver and obesity induced by high-fat diets.     

瘦素改善2型糖尿病ob/ob小鼠糖和脂质代谢作用机制的探讨

目的 研究瘦素对2型糖尿病小鼠糖脂代谢及肝功能的改善作用,并从氧化应激、内质网应激和胰岛素抵抗等方面探讨其可能机制。方法 选用瘦素缺陷的ob/ob小鼠作为2型糖尿病模型,根据是否给予瘦素处理分为两组（1 mg/（kg·d）, 腹腔内注射）;选用野生型C57BL/6J小鼠为正常对照。测定血清甘油三酯（triglyceride,TG）和总胆固醇（total cholesterol,TC）反映脂质代谢状况,血清谷丙转氨酶（alanine transaminase,ALT）和谷草转氨酶（aspartate aminotransferase,AST）反映肝功能; 酶联免疫吸附实验测定胰岛素水平;Western blot检测氧化应激指标还原烟酰胺腺嘌呤二核苷酸磷酸氧化酶 4（nicotinamide adenine dinucleotide phosphate reduced oxidase 4,NOX4）和过氧化氢酶 （catalase,CAT）、内质网应激标志葡萄糖调节蛋白78（glucose-regulated protein 78,GRP78）水平,胰岛素调控糖脂代谢通路蛋白激酶B（protein kinase B,AKT）的激活。结果 与野生型小鼠比较,ob/ob小鼠血糖、TG和TC、ALT和AST活力以及胰岛素水平皆升高（均有P<0.05）;与ob/ob小鼠比较,经瘦素处理的ob/ob小鼠血糖、TG和TC、ALT和AST活力以及胰岛素水平皆下降（均有P<0.05）。与野生型小鼠比较,ob/ob小鼠肝脏NOX4和GRP78水平增高（均有P<0.05）,CAT和p-AKT水平降低（均有P<0.05）;与未经瘦素处理的ob/ob小鼠相比,经瘦素处理的ob/ob小鼠肝脏中NOX4、GRP78降低（均有P<0.05）,CAT和p-AKT升高（均有P<0.05）。结论 瘦素可改善2型糖尿病小鼠糖脂代谢和肝功能,作用机制可能与其减轻肝脏氧化应激和内质网应激以及恢复对胰岛素的敏感性有关。     

Ferulic Acid Prevents Nonalcoholic Fatty Liver Disease by Promoting Fatty Acid Oxidation and Energy Expenditure in C57BL/6 Mice Fed a High-Fat Diet

There is a consensus that ferulic acid (FA), the most prominent phenolic acid in whole grains, displays a protective effect in non-alcoholic fatty liver disease (NAFLD), though its underlying mechanism not fully elucidated. This study aimed to investigate the protective effect of FA on high-fat diet (HFD)-induced NAFLD in mice and its potential mechanism. C57BL/6 mice were divided into the control diet (CON) group, the HFD group, and the treatment (HFD+FA) group, fed with an HFD and FA (100 mg/kg/day) by oral gavage for 12 weeks. Hematoxylin and eosin (H&E) staining and Oil Red O staining were used to evaluate liver tissue pathological changes and lipid accumulation respectively. It was demonstrated that FA supplementation prevented HFD-induced NAFLD, which was evidenced by the decreased accumulation of lipid and hepatic steatosis in the HFD+FA group. Specifically, FA supplementation decreased hepatic triacylglycerol (TG) content by 33.5% (p < 0.01). Metabolic cage studies reveal that FA-treated mice have elevated energy expenditure by 11.5% during dark phases. Mechanistically, FA treatment increases the expression of rate-limiting enzymes of fatty acid oxidation and ketone body biosynthesis CPT1A, ACOX1 and HMGCS2, which are the peroxisome proliferator-activated receptors α (PPARα) targets in liver. In conclusion, FA could effectively prevent HFD-induced NAFLD possibly by activating PPARα to increase energy expenditure and decrease the accumulation of triacylglycerol in the liver.     

Lycopene supplementation suppresses oxidative stress induced by a high fat diet in gerbils

The effect of lycopene supplementation on the antioxidant system was investigated by analyzing lipid peroxide levels, glutathione contents, and antioxidant enzyme activities in Mongolian gerbils fed a high fat diet. Gerbils were fed on each experimental diet for 6 weeks; normal diet (NC), normal diet with 0.05% lycopene (NL), high fat diet (HF), and a high fat diet with 0.05% lycopene (HFL). Dietary supplementation of lycopene increased hepatic lycopene level in gerbils fed a normal or high fat diet (P < 0.05). Liver and erythrocyte concentrations of lipid peroxide increased in gerbils fed a high fat diet, whereas lycopene supplementation decreased liver and erythrocyte concentrations of lipid peroxide (P < 0.05). Hepatic total glutathione content was higher in the NL group than that in the NC group (P < 0.05). Total antioxidant status in plasma increased following lycopene supplementation compared with that of the non-lycopene supplemented groups (P < 0.05). Hepatic catalase activity increased following dietary lycopene supplementation (P < 0.05). Superoxide dismutase activity in liver remained unchanged with lycopene supplementation, but erythrocyte superoxide dismutase activity increased in NL group compared with NC group (P < 0.05). Glutathione-S-transferase activity increased in the NL group compared to NC group (P < 0.05). Liver and erythrocyte glutathione peroxidase activity increased significantly in the NL group compared to that in the HF group (P < 0.05). Liver glutathione reductase activity was higher in the NL group than that in the NC group (P < 0.05). These results suggest that lycopene supplementation may be efficient for preventing chronic diseases induced by oxidative stress related to high fat diet.