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Forkhead box O(Foxos)转录因子在调控机体代谢中发挥重要作用,在种属间高度保守,并受胰岛素信号控制.FoxOs在胰岛素敏感组织如肝脏、胰腺、骨骼肌和胃肠道中表达.在机体能量摄入受限或饥饿状态下,FoxOs位于细胞核内,激活相关基因转录,增加肝脏葡萄糖产生,减少胰岛素分泌,增加采食量,引起骨骼肌降解,为葡萄糖异生提供底物;然而在能量摄入过多或胰岛素抵抗时FoxOs被激活,失去转录调节活性;同时,FoxOs还参与调控细胞分化、增殖和细胞存活.本文综述了FoxOs转录因子控制胰岛素敏感组织中相关基因表达,从而调控机体代谢和组织发育.了解FoxOs转录因子的功能和作用机制,将为调控激素敏感组织发育和机体能量代谢提供依据. 相似文献
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《畜牧与兽医》2020,(2):67-72
为了探究蓝刺头多糖B(ETPB)对棕榈酸(PA)诱导的胰岛素抵抗L6骨骼肌细胞耗糖量及腺苷酸活化蛋白激酶(AMPK)表达的影响,体外培养大鼠L6成肌细胞,诱导分化为骨骼肌细胞并进行分化鉴定;采用CCK8法检测细胞存活率,筛选PA和ETPB的安全浓度;葡萄糖氧化酶法检测各组细胞耗糖量;实时荧光定量PCR法检测AMPK mRNA基因表达水平,Western blot法检测AMPK蛋白表达量。结果显示:PA诱导L6骨骼肌细胞发生胰岛素抵抗的最适造模浓度为0.4 mmol/L,ETPB的最大安全浓度为200 mg/mL;ETPB可显著提高胰岛素抵抗L6骨骼肌细胞耗糖量(P<0.05),上调AMPK mRNA表达水平,增加AMPK蛋白表达量。提示:ETPB可以通过提高AMPK基因及蛋白表达而促进胰岛素抵抗L6骨骼肌细胞耗糖,这可能是ETPB改善骨骼肌胰岛素抵抗的作用机制之一。 相似文献
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本研究旨在探讨地菍总黄酮（TFMD）对胰岛素抵抗（IR）小鼠的干预作用及其机制。试验以灌胃高脂乳剂建立胰岛素抵抗小鼠模型，同时灌胃给予地菍总黄酮混悬液（高剂量（600 mg/kg）、中剂量（300 mg/kg）及低剂量（150 mg/kg））进行治疗，治疗周期为30 d。试验结束后测定小鼠血清中空腹血清胰岛素（FINS）、空腹血糖（FBG）、胰岛素抵抗指数（HOMA-IR）、胰岛素敏感指数（ISI）、血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白（LDL）及高密度脂蛋白（HDL）水平；利用实时荧光定量PCR法检测各组小鼠肝脏中胰岛素受体（InsR）、过氧化物酶体增殖物激活受体-γ（PPAR-γ）及骨骼肌中葡萄糖转运体4（GLUT4）的mRNA表达水平；利用免疫组化技术检测各组小鼠肝脏中InsR、PPAR-γ和骨骼肌中GLUT4的蛋白表达水平。结果显示，与模型组相比，地菍总黄酮能降低IR小鼠的体重，降低血清FBG、FINS及HOMA-IR水平，升高ISI水平（P<0.01，P<0.05）；降低血清TG、TC及LDL含量，升高HDL含量（P<0.01，P<0.05）；同时提高IR小鼠肝脏中InsR、PPAR-γ及骨骼肌中GLUT4的mRNA表达量，提高小鼠肝脏InsR、PPAR-γ及骨骼肌中GLUT4的蛋白表达水平（P<0.01，P<0.05）。以上试验结果证实，地菍总黄酮能有效缓解小鼠试验性胰岛素抵抗症状，该活性与调节糖脂代谢、增强胰岛素敏感性有关。 相似文献
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肝脏中脂肪酸代谢平衡的破坏是肝脂肪变性的主要原因,胰岛素和葡萄糖都能独立调控肝脏中脂肪酸的生成,在这些调控中起重要作用的转录因子如SR EBP-1,C hR EBP,PPAR等与肝脂肪变性的发生有紧密联系。 相似文献
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围产期奶牛由于干物质摄入不足与能量输出增加,产生能量负平衡,导致机体代谢紊乱,引发营养代谢性疾病,阻碍奶牛养殖业的健康发展。胰岛素对肝脏、骨骼肌、脂肪等组织的稳定代谢具有重要调控作用,体内胰岛素通路功能的正常可保证围产期奶牛处于健康状态,降低营养代谢性疾病发生率。通过提高围产期奶牛能量代谢,改善氧化应激及胰岛素相关关键通路和激酶等方式可有效提高胰岛素敏感性,维持葡萄糖和脂质代谢稳态,提高健康状况和生产性能。本文阐述了胰岛素通路调控各组织代谢的作用机制、胰岛素抵抗的发生及对围产期奶牛糖代谢、脂代谢、健康状况和生产性能的影响,并揭示相应的调控措施,为预防围产期奶牛营养代谢性疾病提供理论参考依据。 相似文献
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《蚕业科学》2015,(3)
胰岛素抵抗(insulin resistance,IR)是Ⅱ型糖尿病的重要发病机制之一,且贯穿于Ⅱ型糖尿病的发生与病情发展全过程。利用天然、安全的植物提取物增强机体对胰岛素的敏感性已成为Ⅱ型糖尿病预防和治疗的一个重要策略。已有的研究表明,桑树来源的多羟基生物碱类化合物、黄酮类化合物、多糖类化合物等成分具有降血糖活性,这些活性物质可以调控过氧化物酶体增殖物激活受体-γ(PPARγ)、葡萄糖转运体4(GLUT4)、腺苷酸活化蛋白激酶(AMPK)等的表达及多种信号通路,改善脂肪、肝脏、骨骼肌组织的胰岛素抵抗及抑制胰岛细胞的凋亡等。今后应加强对桑树中可改善胰岛素抵抗的特征性活性组分或单体的分离鉴定,以及从脂质代谢调节的角度研究改善胰岛素抵抗的作用机制。 相似文献
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Fatty acids are thought to supply energy for cell traditionally. Recent studies have shown the effect of fatty acids on cellular growth, development and metabolism. Skeletal muscle is an important place for fatty acids consumption, and it's also the main target where fatty acids play its role. Palmitic acid is closely related to skeletal muscle insulin resistance (IR); Oleic acid can increase skeletal muscle fatty acids oxidation and triglyceride synthesis through peroxisome proliferator activated receptor;Linolenic acid relieves skeletal muscle insulin resistance by increasing glucose utilization; Conjugated linoleic acid (CLA) influences skeletal muscle metabolism via multiple signal passways;Docosahexaenoic acid (DHA) and arachidonic acid (ARA) can significantly change myosine heavy chain gene expression;Eicosapntemacnioc acid (EPA) has some effect on skeletal muscle glucose metabolism,mitochondrial action and Apelin system.This review focuses on the effects of different fatty acids on skeletal muscle.And we will have a better understanding about the diverse regulatory mechanism of various fatty acids, and we also hope that this paper will provide some theoretical foundations for the research and development of fatty acids products. 相似文献
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Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) infection of chickens that are more than a few days old results in asymptomatic cecal colonization with persistent shedding of bacteria. We hypothesized that while the bacterium colonizes and persists locally in the cecum it has systemic effects, including changes to metabolic pathways of skeletal muscle, influencing the physiology of the avian host. Using species-specific peptide arrays to perform kinome analysis on metabolic signaling pathways in skeletal muscle of Salmonella Typhimurium infected chickens, we have observed key metabolic changes that affected fatty acid and glucose metabolism through the 5''-adenosine monophosphate-activated protein kinase (AMPK) and the insulin/mammalian target of rapamycin (mTOR) signaling pathway. Over a three week time course of infection, we observed changes in the phosphorylation state of the AMPK protein, and proteins up and down the pathway. In addition, changes to a large subset of the protein intermediates of the insulin/mTOR pathway in the skeletal muscle were altered by infection. These changes occur in pathways with direct effects on fatty acid and glucose metabolism. This is the first report of significant cellular metabolic changes occurring systemically in chicken due to a Salmonella infection. These results have implications not only for animal production and health but also for the understanding of how Salmonella infection in the intestine can have widespread, systemic effects on the metabolism of chickens without disease-like symptoms. 相似文献
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B. Al‐Trad T. Wittek G. Gäbel M. Fürll K. Reisberg J. R. Aschenbach 《Journal of animal physiology and animal nutrition》2010,94(6):685-695
A positive energy balance in dairy cows pre‐partum may decrease hepatic carnitine palmitoyltransferase (CPT) enzyme activity, which might contribute to disturbances of lipid metabolism post‐partum. The purpose of this study was to investigate whether skeletal muscle CPT activity can also be downregulated during positive energy balance. Mid‐lactating dairy cows were maintained on intravenous infusion of either saline (control) or glucose solutions that increased linearly over 24 days, remained at the 24‐day level until day 28 and were suspended thereafter. Liver and skeletal muscle biopsies, as well as four diurnal blood samples, were taken on days 0, 8, 16, 24, and 32, representing infusion levels equivalent to 0%, 10%, 20%, 30% and 0% of the net energy for lactation (NEL) requirement respectively. Glucose infusion increased serum insulin concentrations on day 16 and 24 while plasma glucose levels were increased at only a single time point on day 24. Serum beta‐hydroxybutyric acid concentrations decreased between day 8 and 24; whereas changes in non‐esterified fatty acids were mostly insignificant. Total lipid contents of liver and skeletal muscle were not affected by treatment. Hepatic CPT activity decreased with glucose infusion (by 35% on day 24) and remained decreased on day 32. Hepatic expression levels of CPT‐1A and CPT‐2 mRNA were not significantly altered but tended to reflect the changes in enzyme activity. In contrast to the liver, no effect of glucose infusion was observed on skeletal muscle CPT activity. We conclude that suppression of CPT activity by positive energy balance appears to be specific for the liver in mid‐lactating dairy cows. 相似文献
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Kirsti Rouvinen-Watt 《Canadian journal of veterinary research》2003,67(3):161-168
Nursing sickness, the largest single cause of mortality in adult female mink (Mustela vison), is an example of a metabolic disorder, which develops when the demands for lactation require extensive mobilization of body energy reserves. The condition is characterized by progressive weight loss, emaciation, and dehydration with high concentrations of glucose and insulin in the blood. Morbidity due to nursing sickness can be as high as 15% with mortality around 8%, but the incidence is known to vary from year to year. Stress has been shown to trigger the onset of the disease and old females and females with large litters are most often affected. Increasing demand for gluconeogenesis from amino acids due to heavy milk production may be a predisposing factor. Glucose metabolism is inextricably linked to that of protein and fats. In obesity (or lipodystrophy), the ability of adipose tissue to buffer the daily influx of nutrients is overwhelmed (or absent), interfering with insulin-mediated glucose disposal and leading to insulin resistance. Polyunsaturated fatty acids of the n-3 family play an important role in modulating insulin signalling and glucose uptake by peripheral tissue. The increasing demand on these fatty acids for milk fat synthesis towards late lactation may result in deficiency in the lactating female, thus impairing glucose disposal. It is suggested that the underlying cause of mink nursing sickness is the development of acquired insulin resistance with 3 contributing key elements: obesity (or lipodystrophy), n-3 fatty acid deficiency, and high protein oxidation rate. It is recommended that mink breeder females be kept in moderate body condition during fall and winter to avoid fattening or emaciation. A dietary n-3 fatty acid supplement during the lactation period may be beneficial for improved glycemic control. Lowering of dietary protein reduces (oxidative) stress and improves water balance in the nursing females and may, therefore, prevent the development and help in the management of nursing sickness. It is also surmised that other, thus far unexplained, metabolic disorders seen in male and female mink may be related to acquired insulin resistance. 相似文献
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The effect of peak lactation on the activities of a number of enzymes of glucose and lipid metabolism of perirenal and subcutaneous adipose tissue, skeletal muscle, liver, kidney cortex and mammary parenchyma of sheep are described. Enzymes studied included hexokinase (glucose utilization), pyruvate carboxylase (gluconeogenesis), pyruvate dehydrogenase (glucose oxidation and production of acetyl CoA for fatty acid synthesis), acetyl CoA carboxylase (fatty acid synthesis) and glycerol-3-phosphate acyltransferase (fatty acid esterification). Major changes that were found include a decrease in activities of enzymes of fatty acid synthesis and esterification in adipose tissues, decreased activity of pyruvate dehydrogenase in muscle and adipose tissues and increased pyruvate carboxylase; there was no change in activities of enzyme of fatty acid esterification in liver. Activities of hexokinase, acetyl CoA carboxylase and glycerol-3-phosphate acyltransferase have been estimated per tissue; this shows the quantitative importance of limiting glucose utilization by muscle and of suppression of fatty acid synthesis in adipose tissue for efficient partitioning of nutrients for milk production. 相似文献
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Ronnel [0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphorothioate] is an organophosphate pesticide with growth-promoting properties. Experiments were conducted to determine effects of ronnel on oxidation of and fatty acid synthesis from acetate and glucose as indices of metabolic activity in subcutaneous adipose tissue and skeletal muscle from 6-, 12- and 18-mo-old steers. Ronnel depressed metabolic activity in adipose tissue from 6- and 12-mo-old steers without concomitantly decreasing metabolic activity in skeletal muscle. Production of CO2 and fatty acids from acetate and glucose in tissues from 18-mo-old steers was influenced less by ronnel than in tissues from younger steers. Interactions of ronnel with thyroxine or growth hormone on acetate oxidation and conversion to fatty acids in adipose tissue also were investigated. Thyroxine increased acetate oxidation and decreased fatty acid synthesis. Ronnel interfered with the metabolic effects of thyroxine. Growth hormone, with or without ronnel, did not affect metabolic activity of adipose tissue. Ronnel seemingly alters the partitioning of acetate and glucose between major metabolic processes in adipose tissue and skeletal muscle. 相似文献
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Although the metabolic actions of insulin in fish have been investigated widely in the past several years, lipid metabolism has received little attention, especially in tissues like the liver or white muscle. In the present study, rainbow trout received insulin treatments both acutely (intraperitoneal injection) and chronically (through mino-osmotic pumps) to elucidate hormone metabolic actions at molecular levels on the 2 main insulin target tissues in trout, namely, liver and muscle. Plasma and free fatty acid concentrations in plasma, as well as mRNA measurements of some key enzymes involved in lipid metabolism, were assessed in these tissues after 6 h and 4 d of acute and chronic insulin treatments, respectively. Our results showed that although fish received the same final total amount of hormone in both treatments, the actions of insulin on lipid metabolism were both time and tissue dependent. After the acute insulin treatment, the main anabolic role of insulin was reflected in decreased plasma free fatty acid concentrations linked to enhanced hepatic lipogenesis. We also found that insulin increased the mRNA levels of enzymes involved in lipid oxidation, perhaps to counteract insulin-induced hypoglycemia. In contrast, our data show that after chronic insulin treatment, liver and muscle exhibit different metabolic strategies: whereas in the liver chronic insulin-induced hypoglycemia may stimulate lipolytic processes to spare glucose stores, the muscle responds directly to the anabolic hormone action by increasing its lipogenic capacity and by inhibiting pathways of lipid oxidation. 相似文献
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J. K. Suagee B. A. Corl K. L. Swyers T. L. Smith C. D. Flinn R. J. Geor 《Journal of animal physiology and animal nutrition》2013,97(2):245-254
High glycaemic feeds are associated with the development of insulin resistance in horses. However, studies that evaluated the effect of high glycaemic feeds used horses that either ranged in body condition from lean to obese or were fed to increase body condition over a period of months; thus, the ability of high glycaemic feeds to induce insulin resistance in lean horses has not been determined. This study evaluated the insulin sensitivity of 18 lean horses fed a 10% (LO; n = 6), 20% (MED; n = 6) or 60% (HI; n = 6) non‐structural carbohydrate complementary feed for 90 days. Although both the MED and HI diets increased insulinaemic responses to concentrate feeding in relation to the LO diet (p > 0.05), neither induced insulin resistance, as assessed by glucose tolerance test, following the 90‐day feeding trial. Interestingly, the post‐feeding suppression of plasma non‐esterified fatty acids was less pronounced in HI‐fed horses (p = 0.054) on days 30 and 90 of the study, potentially indicating that insulin‐induced suppression of adipose tissue lipolysis was reduced. As insulin‐resistant animals often have elevated plasma lipid concentrations, it is possible that altered lipid metabolism is an early event in the development of insulin resistance. The effects of high glycaemic feeds that are fed for a longer duration of time, on glucose and lipid metabolism, should be investigated further. 相似文献