G蛋白偶联受体120研究进展

游离脂肪酸(FFAs)是一种重要能量来源并起到信号分子的作用,外周游离脂肪酸水平升高与糖尿病、肥胖以及脂代谢紊乱紧密相关。G蛋白偶联受体(G protein-coupled re-ceptors,GPCR)是一种含有7个α螺旋的整合膜蛋白,是细胞表面最大的受体超家族。GPR120是一种新发现的游离脂肪酸受体,它直接或者间接参与调节体内一系列代谢过程,如激素分泌、葡萄糖代谢、脂质生成、信号转导等。作为一潜在的治疗多种代谢疾病的药物靶标,GPR120的生理功能及作用的分子机制等都值得进一步研究。     

G蛋白偶联受体120研究进展

游离脂肪酸(FFAs)是一种重要能量来源并起到信号分子的作用,外周游离脂肪酸水平升高与糖尿病、肥胖以及脂代谢紊乱紧密相关.G蛋白偶联受体(G protein-coupled re-ceptors,GPCR)是一种含有7个α螺旋的整合膜蛋白,是细胞表面最大的受体超家族.GPR120是一种新发现的游离脂肪酸受体,它直接或者间接参与调节体内一系列代谢过程,如激素分泌、葡萄糖代谢、脂质生成、信号转导等.作为一潜在的治疗多种代谢疾病的药物靶标,GPR120的生理功能及作用的分子机制等都值得进一步研究.     

GPR120基因及其生物学功能

GPR120是近期发现的G蛋白偶联受体家族(GPCR)的成员,是游离脂肪酸(FFAs)的特异性受体,它在改善胃肠道代谢,维持胃肠道稳态,降低胰岛素抵抗,减轻组织炎症,缓解肝脏脂肪的集聚,治疗糖尿病及肥胖等方面具有显著功效。基于国内外对GPCR的研究报道,本文就GPR120的配体活性、结构特征、组织分布、信号传导通路及生物学功能等作一综述。     

短期限饲对家兔肝脏和骨骼肌脂质代谢的影响

本试验旨在研究短期限饲对家兔肝脏和骨骼肌中脂质代谢相关基因表达的影响,以阐明短期限饲下家兔脂质代谢的调节机制。选取40日龄、体重相近、健康状况良好的商品代伊拉肉兔40只,随机分为对照组(自由采食)和试验组(限饲,饲喂量为对照组的70%左右),每组20个重复(公母各占1/2),每个重复1只。试验期为5 d。结果显示:短期限饲显著降低了家兔肝脏指数(P0.05),有降低家兔后腿肌重量的趋势(P=0.074 3),对家兔前腿肌、背腰肌、总肌肉(前腿肌+后腿肌+背腰肌)重量无显著影响(P0.05)。短期限饲显著降低了血浆中甘油三酯(TG)和极低密度脂蛋白(VLDL)含量(P0.05),对肝脏和背腰肌中TG含量的影响不显著(P0.05)。肝脏中,短期限饲显著降低了脂肪酸合成酶(FAS) mRNA的相对表达量(P0.05),显著上调了肉碱脂酰转移酶1(CPT1)、肉碱脂酰转移酶2(CPT2)、G蛋白偶联受体41(GPR41)、G蛋白偶联受体43(GPR43)、过氧化物酶体增殖物激活受体α(PPARα) mRNA的相对表达量(P0.05);骨骼肌中,短期限饲显著上调了脂蛋白脂肪酶(LPL)、脂肪酸结合蛋白(FABP)、G PR41、G PR43 mRNA的相对表达量(P0.05),显著下调了CPT2 mRNA的相对表达量(P0.05),对CPT1、PPARα、脂肪酸转运蛋白(FATP) mRNA的相对表达量无显著影响(P0.05)。由此得出,短期限饲抑制了家兔肝脏中脂质的合成和外运,促进了脂肪酸在肝脏中的氧化利用,GPR41、GPR43和PPARα参与此过程;短期限饲促进了家兔骨骼肌对脂肪酸的摄取和利用,GPR41和GPR43参与此过程。     

短期限饲对生长肉兔脂肪组织中脂质代谢的影响

本试验旨在研究短期限饲对生长肉兔脂肪组织中脂质代谢相关基因表达和相关信号通路的影响,阐明生长肉兔能量稳态的调节机制。试验选用40日龄、体重相近的伊拉肉兔40只,随机分为2组:对照组(自由采食组)和限饲组(饲喂量是对照组的70%左右),每组20个重复,每个重复1只兔,试验持续5 d。结果表明:1)与对照组相比,短期限饲显著降低了生长肉兔的日增重(P0.05),有降低生长肉兔体内总脂肪沉积量的趋势,对生长肉兔体内肩胛脂肪和肾周脂肪沉积量影响均不显著(P0.05)。2)与对照组相比,短期限饲显著降低了脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶(ACC)、脂蛋白脂酶(LPL)的基因表达(P0.05),却显著升高了过氧化物酶体增殖物激活受体(PPARα、PPARγ)、肉碱脂酰转移酶(CPT1、CPT2)和G蛋白偶联受体(GPR41)的基因表达(P0.05),对激素敏感脂肪酶(HSL)和G蛋白偶联受体(GPR43)的基因表达无显著影响(P0.05)。3)与对照组相比,短期限饲对脂肪中甘油三酯(TG)的浓度和磷酸化的磷酸腺苷激活蛋白酶(AMPK)蛋白表达水平无显著影响(P0.05)。综上,短期限饲可抑制生长肉兔脂肪组织中脂肪酸的合成,促进脂肪酸分解; PPARα和GPR41信号通路可能参与了生长肉兔脂肪组织能量稳态的调节。     

胆汁酸的作用与分子调控机制

很多研究表明,胆汁酸能够促进肠道中胆固醇、脂质和脂溶性维生素的吸收。除此之外,胆汁酸还是一个重要的信号调节分子,能够激活肝脏和胃肠道细胞中特异性核受体、G蛋白偶联受体以及细胞信号传导通路,从而改变与编码调控胆汁酸、葡萄糖、脂肪酸和脂蛋白的合成、代谢、运输以及能量代谢的相关酶(蛋白)的基因表达。文章详细论述了胆汁酸的作用以及胆汁酸作为信号分子的调控机制。     

丁酸对乳腺组织基因表达的调控作用及其机制

丁酸是重要的短链脂肪酸,可作为信号分子结合其受体在机体发挥一些重要的生理作用,如调节乳腺、肝脏及脂肪组织的脂质代谢。丁酸的作用机制是多方面的,其中许多机制与其参与基因表达的调控作用有关。丁酸不仅调节某一个基因的表达,还参与信号通路及基因网络的调节。本文综述了丁酸作为重要的乳成分合成前体物、组蛋白去乙酰酶(DHAC)抑制剂、G蛋白偶联受体的配体对乳腺组织基因表达的调控作用及其相关机制。     

烟酸对脂肪代谢的影响及其作用机制

烟酸(NA)是动物必需维生素之一,在动物三大营养物质代谢中起着至关重要的作用,作为烟酰胺腺嘌呤二核苷酸(NAD)和烟酰胺腺嘌呤二核苷酸磷酸(NADP)的前体,可以在供能代谢反应中传递氢和电子.烟酸具有调节脂肪的作用,能够影响机体的脂肪代谢.烟酸通过脂联素、瘦素和胰岛素等激素和G蛋白偶联受体(GPR109A)、二酰基甘油...     

黑素皮质素受体4(MC4R)基因多态性与动物生长性能的相关性研究

黑素皮质素受体4(Melanocortin 4 receptor,MC4R)是G蛋白偶联受体(G Protein coupled receptors,GPCRs)超家族的一个成员,在动物的体重、能量稳态和采食量的调控中具有重要作用。综述了MC4R基因的结构与定位、生物学功能以及MC4R基因与动物生长性能的相关性研究进展。     

Kisspeptin在鸵鸟间脑内的定位和分布研究

<正>Kisspeptin亦称Metastin,是由黑色素瘤转移抑制基因(Kiss-1基因)编码的肽类激素,为G蛋白偶联受体GPR54的内源性配体。Kisspeptin及其受体在脑和多种器官组织分布,具有影响癌细胞的生长和转移、调节生殖功能和影响内分泌等作用。W.Kuohung等[1]在研究Kisspeptin和其受体GPR54在细胞移行     

脂联素及其受体激动剂在禽脂肪性肝病中的应用展望

脂联素(adiponectin)是一种能参与调控糖和脂质代谢、能量调节、免疫反应以及抵抗炎症、氧化应激和细胞凋亡等多种生理过程的激素。禽脂肪性肝病是由于禽肝脏中脂肪酸合成与酯化、脂肪酸转运、脂肪酸氧化、脂肪分解和利用等代谢途径发生异常, 导致的脂类代谢紊乱、肝细胞脂肪变性和炎症反应。文章介绍了脂联素及其分子结构, 脂联素受体及其参与的信号通路, 并重点阐述了脂联素对肝脏脂质代谢、炎症、氧化应激、肝细胞凋亡与自噬方面的调节作用及机制, 以及脂联素受体激动剂的生理作用。同时, 结合禽脂肪性肝病的发生发展机制, 对脂联素及其受体激动剂的应用前景进行了展望。文章为预防和治疗禽类乃至其他动物的脂肪性肝病提供了新的思路。     

多不饱和脂肪酸的生物学功能及其在鸡生产中的应用研究进展简

多不饱和脂肪酸是一种具有特殊生物学功能的物质,在机体免疫调节、细胞增长、基因调控、脂质代谢及抗癌等方面都具有重要的作用,作者简述了多不饱和脂肪酸的生物学功能及其在鸡生产中的应用研究进展,包括对鸡生产性能、蛋肉品质和免疫机制等方面的调节作用。     

Genetic variants of the unsaturated fatty acid receptor GPR120 relating to obesity in dogs

G protein-coupled receptor (GPR) 120 is an unsaturated fatty acid receptor, which is associated with various physiological functions. It is reported that the genetic variant of GPR120, p.Arg270His, is detected more in obese people, and this genetic variation functionally relates to obesity in humans. Obesity is a common nutritional disorder also in dogs, but the genetic factors have not ever been identified in dogs. In this study, we investigated the molecular structure of canine GPR120 and searched for candidate genetic variants which may relate to obesity in dogs. Canine GPR120 was highly homologous to those of other species, and seven transmembrane domains and two N-glycosylation sites were conserved. GPR120 mRNA was expressed in lung, jejunum, ileum, colon, hypothalamus, hippocampus, spinal cord, bone marrow, dermis and white adipose tissues in dogs, as those in mice and humans. Genetic variants of GPR120 were explored in client-owned 141 dogs, resulting in that 5 synonymous and 4 non-synonymous variants were found. The variant c.595C>A (p.Pro199Thr) was found in 40 dogs, and the gene frequency was significantly higher in dogs with higher body condition scores, i.e. 0.320 in BCS4–5 dogs, 0.175 in BCS3 dogs and 0.000 in BCS2 dogs. We conclude that c.595C>A (p.Pro199Thr) is a candidate variant relating to obesity, which may be helpful for nutritional management of dogs.     

Transition period-related changes in the abundance of the mRNAs of adiponectin and its receptors,of visfatin,and of fatty acid binding receptors in adipose tissue of high-yielding dairy cows

Adipose tissue expresses adipokines, which are involved in regulation of energy expenditure, lipid metabolism, and insulin sensitivity. To adapt for the transition from pregnancy to lactation, particularly in high-yielding dairy cows, adipokines, their receptors, and particular G-protein coupled receptors (GPRs) are of potential importance. Signaling by GPR 41 stimulates leptin release via activation by short-chain fatty acids; GPR 43/109A inhibits lipolysis, and GPR 109A thereby mediates the lipid-lowering effects of nicotinic acid and β–hydroxybutyrate. The aim of this study was to compare the mRNA expression of adiponectin and visfatin, adiponectin receptors 1 and 2 (AdipoR1/2), leptin receptor (obRb), insulin receptor as of the aforementioned GPRs during the transition period in high-yielding dairy cows. Biopsies from subcutaneous fat and blood samples were obtained from 10 dairy cows 1 week before and 3 weeks after calving. For AdipoR1 and AdipoR2 mRNA abundance as well as for leptin concentrations in plasma, a reduction (P ≤ .05) was observed postpartum; for visfatin and putative GPR 109A mRNA abundance in adipose tissue, there was a trend (P < .1) for analogous changes. In contrast, the mRNA content of obRb and GPR 41 in adipose tissue was higher (P ≤ .05) in samples from early lactation than in those from late gestation. Our results indicate decreasing adiponectin sensitivity in adipose tissue after calving, which might be involved in the reduced insulin sensitivity of adipose tissue during early lactation. In addition, visfatin, GPR 41, and GPR 109A may further modulate insulin sensitivity.     

2008-2009年反刍动物营养研究进展Ⅳ.脂肪营养

反刍动物产品是膳食的重要组成,其脂肪品质及脂肪酸组成与人体健康密切相关。笔者综述了2009年在ADSA-ASAS大会、ASAS-CAAV大会和CNKI、PubMed等数据库中与反刍动物脂类营养相关的文献。研究热点主要集中于添加油脂对产品中脂肪组成的调控作用、日粮脂肪在瘤胃的代谢作用、乳腺脂肪酸代谢机制及脂肪代谢相关基因的研究。     

Evidence for functional G-coupled protein receptors 43 and 120 in subcutaneous and intramuscular adipose tissue of Angus crossbred steers

We conducted 3 independent experiments to demonstrate functional G-coupled protein receptor 43 (GPR43) and GPR120 in bovine intramuscular (i.m.) and subcutaneous (s.c.) adipose tissues. We hypothesized that media volatile fatty acids and long-chain fatty acids would affect cAMP-activated protein kinase-alpha (AMPKα) protein expression and cAMP concentrations differently in i.m. and s.c. adipose tissue. Experiment 1: oleic acid (18:1n-9) decreased phosphorylated AMPKα protein (p-AMPKα) and the p-AMPKα/AMPKα protein ratio in i.m. preadipocytes, increased the p-AMPKα/AMPKα protein ratio in bovine satellite cells, and had no effect in s.c. preadipocytes. Experment 2: ex vivo explants from the 5th to 8th longissimus thoracic rib muscle section of Angus crossbred steers were cultured 48 hr in media containing 0.25 µM ciglitizone, 5 mM glucose, and 5 mM acetate, in the absence or the presence of 100 µM oleic acid. Oleic acid increased acetate incorporation into fatty acids and GPR43 gene expression in i.m. adipose tissue (P < 0.05), but oleic acid had no effect on fatty acid synthesis or GPR43 expression in s.c. adipose tissue. Experiment 3: fresh s.c. and i.m. adipose tissue from the 5th to 8th longissimus thoracic rib muscle section of Angus crossbred steers was transferred immediately to 6-well culture plates containing 3 mL of KHB/Hepes/5 mM glucose. Samples were preincubated with 0.5 mM theophylline plus 10 μM forskolin for 30 min, after which increasing concentrations of acetate or propionate (0, 10⁻³, 10^−2.3, and 10⁻³ M) in the absence or the presence of 100 μM oleic acid or 100 µM palmitic acid (16:0) were added to the incubation media. Acetate had no effect on forskolin-stimulated cAMP production in s.c. adipose tissue but decreased cAMP in i.m. adipose tissue (P < 0.05); this indicates a functional GPR43 receptor in i.m. adipose tissue. The combination of 10⁻² M acetate and oleic acid decrease cAMP production in s.c. adipose tissue, consistent with GPR120 receptor activity, but oleic acid and palmitic acid attenuated the depression of cAMP production caused by acetate in i.m. adipose tissue. Palmitic acid depressed cAMP production in s.c. adipose tissue, and increased cAMP production in i.m. adipose tissue (P < 0.05). Propionate had no effect on cAMP production in s.c. or i.m. adipose tissue. These results provide evidence for functional GPR43 receptors in i.m. adipose tissue and GPR120 receptors in s.c. adipose tissue, both of which would suppress lipolysis.     

脂肪酸结合蛋白7的研究进展

脂肪酸结合蛋白7(FABP7)是脂肪酸结合蛋白(FABPs)家族成员之一,FABP7基因对大脑发育及中枢神经系统的调节至关重要。同时,FABP7位于脂质代谢的经典通路PPAR通路中,在脂质代谢、基因调控、细胞生长和分化过程中发挥重要的作用。目前,关于FABP7基因的研究主要集中于大脑发育及中枢神经系统的调节,对于家畜脂质代谢分子机制方面的研究相对较少。本文对FABP7的结构、分布及其在脂质代谢、神经系统和癌细胞增殖相关研究进展进行阐述,为今后利用FABP7基因相关育种研究提供参考。     

Expression of GPR30 and GPR43 in oral tissues: deriving new hypotheses on the role of diet in animal physiology and the development of oral cancers

Food components and salivary hormones modulate the function of various tissues in the oral cavity. However, the mechanisms underlying such interactions are poorly understood. This study aimed at the detection of GPR30 and GPR43 in oral epithelia. Although unknown yet, the expression of these receptors is hypothesized to be fundamental for the actions of salivary oestrogens, dietary isoflavones and short chain fatty acids (SCFA) in the oral environment. Either immunoblotting or RT-PCR techniques were used for receptor detection in bovine and primate oral tissues. Here we show for the first time that mRNA of the G-protein-coupled oestrogen receptor, GPR30, and the short chain fatty acid receptor, GPR43, are expressed in bovine parotid glands. Furthermore, GPR30 protein is expressed in bovine parotid gland and the tongue of the primate Theropithecus gelada. With GPR30 being a target for dietary isoflavones and GPR43 being a suggested target for short chain fatty acids, we propose new hypotheses concerning the receptors' roles in salivary gland physiology and pathology. Our findings may trigger more detailed studies on GPRs to unravel their role in regulatory mechanisms in the oral cavity as well as in cancer development in relation to diets or biologically active compounds like soy isoflavones.