Lipogenic gene expression in abdominal adipose and liver tissues of diet-induced overweight cats

The effect of overweight status on the expression of SREBP-1c and downstream lipogenic genes, such as ATP citrate lyase (ACL) and fatty acid synthase (FAS), in abdominal adipose and liver tissues was determined in cats using a diet-induced weight gain model. ACL and SREBP-1c mRNA expression was significantly reduced (～65% and 20%, respectively) in liver tissue, whereas FAS and SREBP-1c expression was significantly increased (～80% and 45%, respectively) in abdominal omental adipose tissue of overweight animals as compared to healthy animals. Additionally, ACL, FAS, and SREBP-1c expression was significantly reduced by ～50%, 75%, and 70%, respectively, in abdominal subcutaneous adipose tissue of overweight animals. Omental adipose tissue appeared to foster, whereas subcutaneous adipose and liver tissues appeared to defer lipid storage based on differences in SREBP-1c mRNA expression. Overall, reduced lipogenic gene mRNA expression patterns support the hypothesis that SREBP-1c expression is reduced in overweight and possibly obese cats, reflecting down-regulation of the lipogenic pathway to prevent further fat accumulation and weight gain.     

Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high‐fat diet‐fed mice

Animal by‐products can be recycled and used as sources of essential nutrients. Water‐soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high‐fat diet. Exercise‐trained mice had significantly less perirenal adipose tissue, whereas WSHI‐fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone‐sensitive lipase. WSHI‐fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation‐related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism‐related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high‐fat diet.     

基于芯片数据分析关于SREBP-1c调控脂肪代谢过程作用机理的研究

为了研究SREBP-1c作为脂肪代谢过程中重要的核转录因子参与调控动物脂肪代谢过程作用的机理,试验采用显著性差异表达分析及其通路分析在基因表达谱数据库(GEO)中收集到的转录因子SREBP-1c相关的小鼠脂肪组织的转录本芯片数据。结果表明:SREBP-1c是通过一系列的与细胞分化作用相关的靶基因及其通路参与调控脂肪代谢过程的。     

Antibiotics promote abdominal fat accumulation in broilers

Antibiotics stimulate the growth of animals but result in drug residues and bacterial resistance. In this study, the negative effect of antibiotics on abdominal fat deposition was evaluated in broilers. The results showed that adding both chlortetracycline (50 g/1,000 kg) and tylosin (50 g/1,000 kg) significantly increased abdominal fat weight, abdominal fat percentage (p < .05), and triglyceride and cholesterol levels (p < .05) in blood. Also, both products synchronously stimulated intestinal absorption and synthesis of liver fat. The expression levels of the peroxisome proliferator‐activated receptor γ (PPARγ), diacylgycerol acyltransferase 2 (DGAT2), lipoprotein lipase (LPL), and fatty acid‐binding protein (FABP4) genes in abdominal fat tissue significantly increased (p < .05 or 0.01) when antibiotics were added to the feed. However, no significant difference was found in expression of the fatty acid synthesis (FAS) or acetyl CoA carboxylase (ACC) genes. Further in vitro study results revealed that antibiotics had no effect on fat content or the related gene expression levels in preadipocytes. In summary, the antibiotics induced fat deposition in adipose tissues by activating extracellular absorption of fatty acids from intestinal absorption and synthesis of liver fat. However, it shows no direct regulation by adipose tissue.     

Effect of melatonin on visceral fat deposition,lipid metabolism and hepatic lipo-metabolic gene expression in male rats

Melatonin (MT) influences lipid metabolism in animals; however, the mechanistic effect of melatonin on liver fat and abdominal adipose deposition requires further clarity. In order to study the effects of melatonin on lipid metabolism, and hepatic fat and abdominal adipose deposition in animals, twenty Sprague–Dawley (SD) rats of 6 weeks of age with similar bodyweight were randomly divided into two groups: control (CTL) and MT-treated (10 mg/kg/day). During a 60-day experiment, food intake and bodyweight were measured daily and weekly respectively. At the end of treatment, blood samples were collected to collect plasma to quantify hormones and metabolic indicators of lipid metabolism. In addition, organ and abdominal adipose depots including liver, and omental, perirenal, and epididymal fat were weighed. Liver tissue was sampled for sectioning, long-chain fatty acid (LCFA) quantification, and gene chip and Real-time quantitative PCR (qPCR) analyses. The results showed that liver weight and index (ratio of liver weight to body weight) in MT group reduced by 20.69% and 9.63% respectively; omentum weight and index reduced by 59.88% and 54.93% respectively, and epididymal fat weight reduced by 45.34% (p = 0.049), relative to CTL. Plasma lipid indices, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC) with MT treatment decreased significantly compared with the control. Fat and 8 LCFA content in liver in MT group also decreased. Gene chip and qPCR demonstrated that there were 289 genes up-regulated and 293 genes down-regulated by MT. Further analysis found that the mRNA expression of lipolysis-related genes increased, while the mRNA expression of lipogenesis-related enzymes decreased (p < 0.05) with MT. This study concluded that melatonin greatly affected fat deposition, and hepatic LCFA supply and the expression of genes associated with lipogenesis and lipolysis.     

In ovo leptin administration affects hepatic lipid metabolism and microRNA expression in newly hatched broiler chickens

Background: A leptin-like immunoreactive substance has been found in chicken eggs and has been implicated in serving as a maternal signal to program offspring growth and metabolism. In the present study, we investigated the effects of in ovo leptin administration on hatch weight, serum and hepatic concentrations of metabolites and hormones, as well as on the expression of genes involved in hepatic lipid metabolism and the predicted microRNAs (miRNAs) targeting the affected genes. To this end we injected fertile eggs with either 0.5 μg of recombinant murine leptin or vehicle (PBS) before incubation. Results: Prenatally leptin-exposed chicks showed lower hatch weight, but higher liver weight relative to the body weight, compared to the control group. In ovo leptin treatment increased the hepatic content and serum concentration of leptin in newly hatched chickens. The hepatic contents of triglycerides (TG) and total cholesterol (Tch) were decreased, whereas the serum levels of TG, Tch and apolipoprotein B (ApoB) were increased. The hepatic mRNA expression of sterol regulator element binding protein 1 (SREBP-1c), SREBP-2, hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and cholesterol 7α-hydroxylase 1 (CYP7A1) was significantly up-regulated, as was the protein content of both SREBP-1c and SREBP-2 in hepatic nuclear extracts of leptin-treated chickens. Moreover, out of 12 miRNAs targeting SREBP-1c and/or HMGCR, five were significantly up-regulated in liver of leptin-treated chicks, including gga-miR-200b and gga-miR-429, which target both SREBP-1c and HMGCR. Conclusions: These results suggest that leptin in ovo decreases hatch weight, and modifies hepatic leptin secretion and lipid metabolism in newly hatched broiler chickens, possibly via microRNA-mediated gene regulation.     

DHA对高脂饲粮诱导肝脏脂肪积累的预防作用

【目的】探索二十二碳六烯酸(DHA)对高脂饲粮诱导肝脏脂肪积累的预防机制。【方法】将32只雄性SPF级C57BL/6小鼠均分为4组,对照组(Con)饲喂普通饲粮,模型组(Model)饲喂高脂饲粮,DHA组分别在高脂饲粮中添加0.2 g DHA(DHAL)和1.0 g DHA(DHAH),饲喂周期为20周。饲喂期间每天称量体重及食物重量,计算摄食量;饲喂结束,采集肝脏和血液,ELISA法检测肝脏脂联素和血清甘油三酯(TG)的含量,实时荧光定量PCR检测新生脂肪合成关键酶(SREBP-1c、FAS)、脂肪酸氧化关键基因(PPARα、PPARγ、CPT-1A和ACOX)、线粒体基因(PGC-1α)、褐色脂肪化基因(Prdm16、UCP1)的表达,Western blotting法检测肝脏磷酸化ACC、AMPK和AKT蛋白的表达。【结果】与Con组相比,Model组终体重、体脂重量和TG含量均显著增加(P<0.05),肝脏脂联素浓度显著降低(P<0.05)。与Model组相比,DHAL和DHAH组终体重、体脂重量和TG含量均显著降低(P<0.05),肝脏脂联素水平显著增加(P...     

风柜斗草提取物通过调控脂质代谢改善小鼠肝脂质沉积症

旨在探究风柜斗草提取物(Sarcopyramis napalensis Wall extract,SNE)对蛋氨酸胆碱缺乏(MCD)饮食诱导的肝脏脂质沉积的作用与机制。本研究将60只雄性C57BL/6小鼠随机分为6组,每组10只,设置MCS组(MCD饲料的对照饲料组)、MCS+风柜斗草提取物组(400 mg·(kg·bw)^-1)、MCD组、MCD+风柜斗草提取物低、中、高剂量组(100、200、400 mg·(kg·bw)^-1),造模及药物干预6周。进行肝组织切片HE染色、天狼猩红染色,检测血清碱性磷酸酶(AKP)、谷草转氨酶(AST)、谷丙转氨酶(ALT),肝组织谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活力水平及丙二醛(MDA)含量以评估肝脂质沉积、肝纤维化以及肝抗氧化情况。使用Western blot技术检测腺苷酸激活蛋白激酶(AMPK)蛋白的激活情况,使用qRT-PCR技术检测固醇调节元件结合蛋白-1C (SREBP-1c)、肝型脂肪酸结合蛋白(L-FABP)、脂肪酸转运蛋白-3(FATP-3)、脂肪酸转运蛋白-4(FATP-4)、细胞间黏附分子-l (ICAM-1)、血管细胞黏附分子-l (VCAM-1)、基质金属蛋白酶-2(MMP-2)、组织金属蛋白酶抑制剂-2(TIMP-2) mRNA表达水平,同时采用LC-MS/MS技术进行肝组织非靶向脂质组学分析。结果表明,给予200、400 mg·(kg·bw)^-1剂量的风柜斗草提取物时均可显著改善MCD饲料饲喂的小鼠肝脂肪变性,减少炎症簇以及肝纤维化程度。给予风柜斗草提取物100、200、400 mg·(kg·bw)^-1时均可显著降低MCD饲料饲喂的小鼠血清中ALT和AKP的活力以及肝组织中MDA的含量,显著提高小鼠肝中GSH-Px的活力。Western blot及qRT-PCR检测结果显示,风柜斗草提取物显著激活MCD饲料饲喂的小鼠肝组织AMPK;显著抑制MCD饲料饲喂的小鼠肝组织SREBP-1c、L-FABP、FATP-3、FATP-4、ICAM-1、VCAM-1、MMP-2、TIMP-2的mRNA表达水平。肝脂质组学检测结果显示,风柜斗草提取物显著降低MCD饲料饲喂的小鼠肝中甘油三酯(TG)、磷脂酰甘油(PG)以及神经酰胺(Cer)的相对含量;显著提高鞘磷脂(SM)以及辅酶Q9相对含量。结果提示,风柜斗草提取物可通过AMPK/SREBP-1c途径抑制TG合成,以及通过抑制FATP与L-FABP表达来减少肝对脂肪酸的摄取,从而改善MCD饲料饲喂的小鼠肝脂肪变性;通过提高MCD饲料饲喂的小鼠肝组织中SM和辅酶Q9相对含量以及降低Cer相对含量,改善肝细胞氧化应激损伤情况,进而改善MCD饮食诱导的小鼠肝炎症和纤维化,最终达到改善肝脂质沉积症的作用。     

日粮蛋白质水平对乌金猪肝脏组织脂类代谢相关基因表达的影响

为探讨日粮蛋白质水平对乌金猪肝脏组织脂类代谢相关基因表达的影响,试验选取体重约15 kg的乌金猪54头,随机分为3组,每组18头,为低、中和高蛋白质组,其在15～30、30～60及60～100 kg生长阶段的蛋白质水平分别为14%、12%、10%,16%、14%、12%和18%、16%、14%。猪在体重为30、60和100 kg时屠宰,取其肝脏组织,Real-time PCR定量检测脂类代谢相关基因的表达水平。结果显示,在30、60和100 kg时,乌金猪肝脏组织中ACC、FAS、SREBP-1C基因的表达水平均随着蛋白质水平的升高而降低;CPT-Ⅰ和PPARα基因的表达水平则随着蛋白质水平的升高而升高。由此表明,日粮高蛋白质水平显著降低肝脏脂肪酸合成代谢基因(ACC、FAS和SREBP-1C)的表达(P<0.05),提高脂肪酸分解代谢基因(CPT-Ⅰ和PPARα)的表达水平(P<0.05);脂肪酸合成减少,且被氧化的量增加,两者共同作用导致用于合成甘油三酯(TG)的脂肪酸含量降低,从而减少了从肝脏组织被运输到各个组织的TG含量,使机体沉积TG的能力降低。     

Comparative analysis of differentially expressed genes related to triglyceride metabolism between intramuscular fat and abdominal fat in broilers

ABSTRACT

1. Lipid metabolism is an indispensable process in an organism, though little is known about the regulatory mechanisms of fat deposition in different types of adipose tissues.

2. The differentially expressed genes related to triglyceride (TG) metabolism between abdominal and intramuscular fat (IMF) of Beijing-You chickens were investigated in this study.

3. TG content in abdominal fat (AF) (349.7 mg/g) was significantly higher (P < 0.01) than in the breast and thigh (12.3 mg/g and 24.8 mg/g, respectively).

4. Using Agilent chicken gene-expression profiling in adipose tissues between AF and muscle (breast and thigh), certain representative genes related to fatty acid metabolism, lipoprotein catabolism and esterification reactions were significantly upregulated (P < 0.05 or P < 0.01).

5. Genes involved in fatty acid oxidation or carbohydrate utilisation were significantly up- or downregulated (P < 0.05 or P < 0.01), including those involved with highly enriched pathways of lipid metabolism (PPAR, Wnt pathway and inositol phosphate metabolism), cell junctions (focal adhesion and regulation of actin cytoskeleton) and muscle contraction.

6. Overall, higher TG levels were observed in AF tissue than in adipose tissues of breast and thigh, which could be regulated through gene expression of pathways related to lipid metabolism (PPAR, Wnt pathway and inositol phosphate metabolism), cell junctions (focal adhesion and regulation of actin cytoskeleton) and muscle contraction. These results provide clues to understanding the molecular mechanisms of TG metabolism between abdominal and IMF.     

Dietary conjugated linoleic acid alters fatty acid composition of pig skeletal muscle and fat

The dietary dose responsiveness of conjugated linoleic acid (CLA) addition relative to the fatty acid profile of edible lean tissue was examined in grower pigs treated with or without porcine somatotropin (pST). Gilts and barrows were fed CLA at 0, 0.25, 0.5, 1.0, or 2.0% of diet by weight from 20 to 55 kg BW. Additional pigs were administered (pST) at 0 or 100 microg x kg BW x d(-1) and fed either 0.5 or 2.0% CLA. Animals were fed diets containing 18% CP, 1.2% lysine, and 3.5 Mcal of DE/kg at 110% of ad libitum intake. The fatty acid profile in latissimus dorsi and dorsal s.c. adipose tissue samples was determined by gas chromatography. Dietary CLA replacement of corn oil increased the percentage of total fatty acids as stearic acid, whereas the percentages as oleic and linolenic acids were reduced in lattisimus muscle. Treatment with CLA + pST increased the percentages of linoleic and arachidonic acids while reducing the percentages of palmitic and oleic acids in lattisimus muscle. Dietary CLA increased the percentages of palmitic and stearic acids in s.c. adipose tissue while reducing the percentages of oleic, linoleic, linolenic, and arachidonic acids. The percentage of palmitic acid was reduced in s.c. adipose tissue, whereas linoleic acid was increased with CLA + pST. No synergistic effect was detected between CLA and pST for reducing carcass lipid content in grower pigs. However, pST increased the percentage of polyunsaturated fatty acids in lattisimus muscle and s.c. adipose tissue while reducing the percentages of saturated fatty acids in swine fed CLA.     

Insulin and dexamethasone regulate stearoyl-CoA desaturase mRNA levels and fatty acid synthesis in ovine adipose tissue explants

Sheep adipose tissue explants were maintained in culture for 24 h in the presence of insulin, dexamethasone, or insulin and dexamethasone, and stearoyl-CoA desaturase (SCD) messenger RNA (mRNA) levels and fatty acid synthesis were measured. Insulin increased SCD mRNA levels (P = 0.008) and synthesis of both saturated (P = 0.07) and unsaturated (P < 0.001) fatty acids but had the greatest effect on unsaturated fatty acid synthesis, resulting in the overall production of a greater (P < 0.001) proportion of monounsaturated fat. Dexamethasone, alone, had the opposite effect but actually potentiated the effect of insulin in stimulating SCD expression and both saturated and monounsaturated fatty acid synthesis, without affecting the relative proportions of each. Across adipose tissue depots, the effect of hormones was similar, although the increase in SCD mRNA levels (P = 0.008) and monounsaturated fatty acid synthesis (P < 0.001) was greater in subcutaneous adipose tissue than in the internal (omental and perirenal) depots. These data clearly show that, in ovine adipose tissue, changes in SCD gene expression in response to insulin and dexamethasone are associated with changes in monounsaturated fatty acid synthesis and suggest that it may be possible to develop strategies to manipulate sheep tissues to produce a less-saturated fatty acid profile.