运动对老年肥胖大鼠脂联素的影响

目的：探讨运动对老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达、血浆脂联素浓度及胰岛素抵抗的影响。方法：取雄性SD大鼠,鼠龄21 d,分青春期、壮年期和老年期三个阶段喂养高脂饲料（脂肪率为36.3%~40.0%）,建立老年肥胖模型。鼠龄达到60周后,取自然生长老年大鼠随机分为对照组（C）和老年运动组（AE）,n=6;取老年肥胖大鼠随机分为肥胖对照组（OC）和肥胖运动组（OE）,n=6。动物跑台坡度0°,运动速度及时间为（15 m/min×15 min）,4组/次,组间休息5 min,每次共运动60 min,5次/周,持续运动8周。8周后,检测内脏脂肪组织脂联素mRNA和蛋白质表达,测定血糖、血浆脂联素浓度和胰岛素浓度,计算胰岛素抵抗。结果：运动干预后,与对照组比较,肥胖对照组大鼠脂联素mRNA和蛋白质表达显著减低,血糖浓度和胰岛素抵抗明显增高;而老年运动组大鼠脂联素mRNA和蛋白质表达显著增高。与肥胖对照组大鼠比较,肥胖运动组大鼠脂联素mRNA和蛋白质表达显著增高、血浆脂联素水平增高,血糖浓度和胰岛素抵抗明显减低。结论：老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达均降低,伴随胰岛素抵抗、血糖升高。运动能显著增加其内脏脂肪组织脂联素mRNA和蛋白质表达,升高血浆脂联素水平,改善胰岛素抵抗,降低血糖。     

运动干预对肥胖机体体内瘦素等脂肪细胞因子作用的影响

肥胖是近年主要的流行病之一,是危害健康的全球公共卫生问题。肥胖是一种慢性低度全身性炎症,伴随着一些炎性细胞的浸润和改变,并存在脂肪细胞因子分泌紊乱。瘦素是由白色脂肪细胞分泌的一种蛋白类激素,也是促炎细胞因子,在调控体内能量与代谢等方面发挥重要作用。运动干预会使肥胖机体体内促炎因子(瘦素、TNF-α、IL-6)水平含量降低,抗炎因子(脂联素)水平含量升高。运动能够延缓肥胖机体体内炎症反应的发生。本文以体内瘦素的生理功能及作用机制为中心,系统综述了运动对肥胖性慢性炎症的调节,主要包括脂肪细胞因子瘦素、脂联素、IL-6、TNF-α,以此探讨运动干预减重降脂和减轻慢性炎症反应的机制,为防治慢性代谢性疾病提供新视角。     

反式脂肪酸对肥胖大鼠氧化还原态的影响

目的：利用高脂饲料建立大鼠肥胖模型,通过对添加不同剂量反式脂肪酸（TFAs）喂养的大鼠脑及血液氧化损伤相关指标比较,探讨TFAs对肥胖大鼠脑和血液抗氧化系统的影响机制。方法：健康雄性SD大鼠40只,随机分为4组：对照组（CON组）、喂饲基础饲料、饮食诱导的肥胖组（DIO组）,喂饲高脂饲料,1%及8%反式脂肪酸组（1% TFAs、8% TFAs组）喂饲添加1% TFAs及8% TFAs的高脂饲料。8周后,心脏取血后,处死动物,留取脑组织及血液以检测相关指标。结果：不同饲料喂养8周后,8% TFAs组大鼠脑丙二醛（MDA）含量明显高于CON组、 DIO组与1% TFAs 组（P<0.01）;CON组、DIO组、1% TFAs及8% TFAs组大鼠脑还原型谷胱甘肽（GSH）含量依次显著下降,差异有统计学意义（P<0.01）;1% TFAs组大鼠血清谷胱甘肽过氧化物酶（GSH-PX）活力低于DIO组、CON组（P<0.05）;与CON组相比,8% TFAs组大鼠脑核因子E2相关因子2（Nrf2）mRNA表达水平显著上调（P < 0.01）;8% TFAs组血红素加氧酶-1（HO-1）蛋白表达水平显著高于CON组（P<0.05）、DIO组（P<0.05）及1% TFAs组（P<0.01）。结论：高含量TFAs摄入可引起肥胖大鼠血液和脑发生氧化损伤,上调氧化损伤相关基因和蛋白表达。     

Orexin-A在肥胖大鼠摄食和自由活动中的调控

目的:探讨Orexin-A对肥胖大鼠摄食和自由活动的影响。方法:雄性SD大鼠下丘脑外侧区(LH)置管,预先测量体重(BW),脂体重(FM)和瘦体重(LM),据此对大鼠分组并分别提供高脂(HF)和低脂(LF)饮食饲喂,通过置管向大鼠LH注射人工合成脑脊液(a CSF)或orexin-A(OXA)。在饲喂前后监测OXA对大鼠自发动态运动(SPA)以及摄食量,体重(BW),脂体重(FM)和瘦体重(LM)的影响,以及每日LH注射OXA是否能够抵抗高脂饮食引起的摄食诱导肥胖(DIO)。结果:高脂饮食饲喂之后,高摄食诱导肥胖(DIO)大鼠和低DIO大鼠间体重增加量(ΔBW)、摄食量和高脂饮食饲喂后的体重无差异(P0.05),但与低脂饮食组大鼠相比,上述各指标均显著增加(P0.05)。低DIO大鼠的24 h SPA和活跃期SPA显著高于高DIO大鼠(P0.05)。LH注射OXA可使严重DIO降低而轻微DIO增加,DIO程度对LH注射OXA后的SPA的影响呈非线性的。每日双侧LH注射OXA可抑制早期DIO但并不改变大鼠摄食量。LH注射OXA使大鼠SPA增加,影响能量消耗,有助于DIO抵抗。结论:Orexin-A可通过增加大鼠活动量,调控肥胖大鼠的摄食和DIO抵抗作用。     

高脂饮食及运动对2型糖尿病大鼠脂联素、瘦素及血糖水平的影响

目的：观察高脂饮食及运动对糖尿病大鼠脂联素、瘦素及血糖水平的影响。方法：选取SD清洁大鼠80只,雌雄各半,随机分为5组（n=16）：空白对照组（A）,普通饮食组（B）,高脂饮食组（C）,普通饮食干预组（普通饮食+运动干预,D）,高脂饮食干预组（高脂饮食+运动干预,E）;除空白组外,其余四组均给予高糖高脂饲料喂养6周后,腹腔链脲佐菌素（30 mg/kg）制备2型糖尿病模型（T2DM）;大鼠建模后,空白组、普通饮食组及普通饮食干预组给予常规饲料,高脂组及高脂饮食干预组大鼠给予高脂饲料,普通饮食干预组及高脂饮食干预组给予运动干预,采用滚筒训练器进行运动,运动频率为每天1次,每周6次,持续6周。6周后测量大鼠脂联素、瘦素、血糖及相关生化指标。结果：除空白组外,其余四组大鼠实验后脂联素水平明显降低（P<0.05）、瘦素、血糖、糖化血红蛋白、甘油三酯明显升高（P<0.05）;高脂饮食组大鼠瘦素、血糖、糖化血红蛋白、甘油三酯水平明显高于高脂饮食干预组（P<0.01）;高脂饮食干预组大鼠瘦素、血糖、糖化血红蛋白、甘油三酯水平高于普通饮食组（P<0.05）;普通饮食组瘦素、血糖、糖化血红蛋白、甘油三酯水平高于普通饮食干预组（P<0.05）;T2DM大鼠模型各组瘦素、血糖、糖化血红蛋白、甘油三酯水平均明显高于对照组（P<0.01）。高脂饮食组大鼠脂联素水平明显低于高脂饮食干预组（P<0.01）;高脂饮食干预组脂联素水平低于普通饮食组（P<0.05）;普通饮食组脂联素水平低于普通饮食干预组（P<0.05）;T2DM大鼠模型各组脂联素水平均明显低于对照组（P<0.01）。脂联素与血糖,瘦素与血糖均有相关性（R<-0.06/R>0.06,P<0.05）。结论：严格的饮食控制及运动有助于控制2型糖尿病大鼠血糖水平的稳定,其可能与控制调节大鼠体内瘦素及脂联素水平有关。     

Orexin-A对高脂饮食诱导肥胖大鼠摄食和体重的影响

目的:探讨Orexin-A对高脂饮食诱导的肥胖大鼠摄食和体重的影响。方法:通过检测SD大鼠24 h动态SPA的分布情况来定义HA大鼠和LA大鼠,创建饮食诱导肥胖(DIO)大鼠模型,向HA和LA大鼠延髓外侧下丘脑(rLH)和黑质多巴胺致密部(SN))微量注射orexin-A,观察orexin-A对能量消耗、自发动态运动(SPA)的作用,以及动态SPA对饮食诱导肥胖(DIO)的抵抗作用。结果:雄性SD大鼠在标准饮食情况下,24 h动态SPA呈正偏态分布,非固定SPA(ambulatory SPA)与瘦体重(lean mass,LM)(P0.05)以及总体重(P0.05)显著相关。HA和LA大鼠(high and low activity rats)间的固有SPA(intrinsic SPA)差异有显著统计学意义(P0.05)。与LA大鼠相比,HA大鼠延髓外侧下丘脑(rLH)和黑质多巴胺致密部(SN)的orexin-A反应性更高。在r LH和SN注射orexin-A能显著增加动态SPA(r LH:P0.05;SN:P0.05)。在HA和LA大鼠的r LH注射orexin-A,每种剂量与注射相同剂量的a CSF的大鼠相比效果有显著差异。而对于SN注射OXA,只有注射高剂量OXA的HA大鼠,与对照组相比,才出现著差异。在r LH注射OXA后,对HA/LA大鼠动态SPA均有显著影响(P0.05)。HA大鼠比LA大鼠能量消耗更高。不同的饮食对于HA和LA大鼠转化为SPA有不同的影响,HA大鼠对DIO敏感性低于LA大鼠。与LA大鼠相比,在LF(Low Fat)饮食条件下,转化为脂肪量的热量更少。结论:Orexin-A可通过增加大鼠活动量,使高脂饮食诱导的肥胖大鼠体重减轻。     

不同强度电针对肥胖大鼠脂肪组织炎症相关因子的影响

探讨不同强度电针对肥胖大鼠脂肪组织核因子-κBp65(NF-κBp65)、单核细胞趋化蛋白-1(MCP-1)和肿瘤坏死因子-α(TNF-α)的作用差异.将SD大鼠随机分为普通饮食组、高脂饮食组、5 V电针组、2.5 V电针组,除普通饮食组外其余各组大鼠均饲以高脂饲料.取"足三里"、"三阴交"穴,不同强度电针治疗14 d后,用蛋白质印迹技术(Western blot)检测肥胖大鼠附睾脂肪组织NF-κBp65的表达,酶联免疫吸附法(ELISA)检测肥胖大鼠附睾脂肪组织MCP-1、TNF-α的含量.研究发现两电针组肥胖大鼠体重、Lee’s指数、脂肪组织中NF-κBp65表达、MCP-1和TNF-α含量较高脂饮食组显著降低(P<0.01),5 V电针组较2.5 V电针组下降效果更为明显(P<0.01,P<0.05).结果表明电针可改善肥胖脂肪组织炎症反应状态,减轻肥胖大鼠体重,且5 V电针组效果优于2.5 V电针组.     

白藜芦醇对高脂饲养小鼠脂肪组织氧化还原状态及血脂的影响

本研究旨在探索白藜芦醇(RSV)对不同程度肥胖小鼠脂肪氧化应激状态和血脂的影响。高脂日粮(HFD)处理12周的昆明小鼠分为3类:肥胖抵抗(DIO-R)、中体重(Med)和肥胖(DIO),分别饲喂HFD、HFD+0.3 g/kg RSV和HFD+0.6 g/kg RSV日粮18周,并以正常日粮小鼠为对照。结果表明,0.6 g/kg RSV处理可显著降低DIO小鼠体重、腹脂率,显著提高脂肪组织抗氧化能力,改善血脂。0.3 g/kg RSV处理对DIO-R小鼠也有类似趋势,但0.6 g/kg RSV处理引起DIO-R小鼠脂肪组织抗氧化能力下降、血脂紊乱。总之,RSV在不同程度肥胖小鼠具有剂量特异性的氧化应激调控作用。     

黄芪水提取物减轻高脂饮食引起的小鼠肥胖

目的:研究黄芪水提取物(Astragalus radix extract,ARE)对高脂饮食(High fat diet,HFD)引起的小鼠肥胖的作用及可能机制。方法:将30只C57 BL/6小鼠随机分为正常喂养组(ND组,n=10)、高脂喂养组(HFD组,n=10)和高脂喂养+黄芪水提取物处理组(ARE组,n=10)。记录三组小鼠体重及食物摄入。在喂养16周时,对小鼠附睾白色脂肪称重,并进行HE染色观察脂肪细胞大小;对小鼠肝脏进行进行HE染色观察肝脏脂肪变性情况。应用ELISA方法检测血清瘦素及脂联素水平。应用Western Blot检测脂肪组织过氧化物酶体增殖物激活受体γ(Peroxisome proliferator activated receptorγ,PPARγ)表达。结果:1与ND组相比,HFD组体重及热量摄入均显著增加,表明肥胖模型建立成功;ARE处理组的体重较HFD组显著下降,但其热量摄入与HFD组相当。2与ND组相比,HFD组白色脂肪组织重量增加、脂肪细胞增大、肝细胞出现显著脂肪变性;ARE处理组上述指标较HFD组明显改善。3与ND组相比,HFD组瘦素水平升高、脂联素水平下降;ARE处理组与HFD组相比,瘦素水平降低、脂联素水平升高。4与ND组相比,HFD组PPARγ表达显著增加,而ARE处理组较HFD组PPARγ表达下降。结论:黄芪水提取物可能通过抑制PPARγ减轻高质饮食引起的肥胖。     

高脂饮食诱导的C57BL／6J肥胖小鼠脂肪组织RIP140基因表达水平的研究

目的：探讨高脂饮食致肥胖小鼠脂肪组织RIP140mRNA表达水平的变化及其与胰岛素抵抗的关系。方法：将C57BL／6J雄性小鼠随机分为正常饮食（NFD）组、高脂饮食（HFD）纽分别喂养14周后,测量两组小鼠体重,以NFD组小鼠体重作为对照,选取HFD组中体重大于对照组小鼠平均体重20％的小鼠作为肥胖组小鼠。对照组和肥胖组小鼠取血测甘油三酯（TG）、总胆固醇（TC）、空腹血糖（FBG）、空腹胰岛素水平（FIns）,计算稳态模型胰岛素抵抗指数（HOMA-IR）;采用RT—PCR技术检测两组小鼠附睾脂肪组织RIP140 mRNA的表达水平,并进行统计学分析。结果：HDF组小鼠中有12只符合标准计入肥胖组。肥胖组小鼠TG、TC、FBG、Fins（P〈0．05）,HOMA-1R（P〈0．01）均明显高于对照组;肥胖组小鼠脂肪组织RIP140mRNA的表达高于对照组,差异具有统计学意义（P〈0．05）;相关分析显示小鼠脂肪组织R1P140 mRNA表达水平与TG水平呈正相关（r=0．536,P〈0．05）,与胰岛素抵抗指数呈正相关（r=0．465,P〈0．05）,而与TC、FBG、Fins水平相关分析无统计学意义（P〉0．05）。结论：高脂饮食诱导的肥胖小鼠脂肪组织RIP140 mRNA表达增加,并与胰岛素抵抗程度呈正相关。     

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.     

Serum and gene expression levels of leptin and adiponectin in rats susceptible or resistant to diet-induced obesity

The aim of the present study was to identify the role of leptin and adiponectin in the development of resistance or susceptibility to diet-induced obesity in rats. For this purpose, male Wistar rats were fed with standard laboratory diet (control group) or cafeteria diet. After 15 days, two groups of rats with different response respect to the cafeteria diet were identified, and were assigned as diet-induced obesity (DIO) and diet resistant (DR) rats. The high-fat diet induced a very significant increase in both body and fat mass weight in DIO group. However, DR rats, gained even less weight than control-fed animals. Food intake was increased in cafeteria-fed rats (both DIO and DR) in comparison to control group; but hyperphagia was higher in DIO rats. In addition, feed efficiency (the ratio of weight gained to calories consumed) was significantly decreased in DR as compared to DIO rats. Regarding leptin, a significant increase in both adipose tissue gene expression and serum levels was observed in DIO rats in comparison with other groups (control and DR). A significant increase in both adiponectin circulating levels and adipose tissue mRNA expression was also observed in DIO animals as compared with the other groups. These data suggest that the susceptibility to obesity of DIO rats might be secondary, at least in part, to an earlier development of leptin resistance, which could lead to alterations in food intake (hyperphagia) and energetic metabolism. However, neither changes in leptin or adiponectin seem to be involved in the adaptive mechanisms that confer resistance to high fat intake.     

食源性肥胖对SD大鼠卵泡发育相关激素及瘦素水平的影响

目的:通过建立大鼠肥胖模型,检测其血脂水平与一系列卵泡发育相关激素指标,试探讨肥胖对大鼠卵泡发育相关激素的影响及可能机制。方法:从30只6-7周龄的SD雌性大鼠中随机选取10只采用普通饲料饲养8周作为对照组(con组);其余20只采用高脂饲料饲养2周,再从中选取体质量增长较快的10只大鼠,继续高脂饮食饲养6周,作为肥胖组(orl组)。第8周末,称量两组大鼠体质量后,禁食水24小时,次日用断尾法采血,离心分离血清,应用化学发光法检测血清雌激素(Eestrogen,E2)、卵泡刺激素(Follicle-Stimulating Hormone,FSH)、黄体生成素(Luteinizing Hormone,LH)、睾酮(Testosterone,T)、瘦素(Leptin)及血脂水平。结果:1.肥胖组大鼠的血清血脂Leptin水平较对照组明显升高;2.肥胖组大鼠血清T水平较对照组明显升高3.肥胖组大鼠血清Leptin水平较对照组明显升高,差异无显著性;4.肥胖组大鼠血清LH水平较对照组稍降低,差异无显著性;5.肥胖组大鼠血清E2、FSH水平与对照组水平相当,无显著变化。结论:高脂饮食诱导的肥胖可能会引起大鼠一系列激素水平的变化,进而影响卵泡发育,这可能与瘦素水平升高有关。     

Diet-induced obese rats exhibit impaired LKB1-AMPK signaling in hypothalamus and adipose tissue

AMPK not only acts as a sensor of cellular energy status but also plays a critical role in the energy balance of the body. In this study, LKB1-AMPK signaling was investigated in diet-induced obese (DIO) and diet resistant (DR) rats. In hypothalamus, DIO rats had lower level of LKB1, AMPKα and pAMPKα than chow-fed or DR rats. Both orexigenic peptide NPY and anorexigenic peptide POMC expression were reduced in hypothalamus of DIO rats. i.c.v. injection of AICAR, an activator of AMPK, increased NPY expression but did not alter POMC expression in DIO rats. In periphery, LKB1 protein content and pAMPKα level were lower in the adipose tissue of DIO rats compared to chow-fed and DR rats. Moreover, pAMPKα and LKB1 protein levels obtained from epididymal fat pad were inversely correlated with epididymal fat mass. LKB1 protein content and pAMPKα in skeletal muscle of DIO rats were not different from those in the muscles of chow-fed and DR rats. In summary, DIO rats, but not DR rats, have impaired LKB1-AMPK signaling in hypothalamus and adipose tissue, suggesting the disturbed energy balance observed in DIO rats is related with abnormalities of AMPK signaling in a tissue specific manner.     

高脂饮食诱导肥胖易感和肥胖抵抗的表型差异

超重与肥胖是许多代谢相关疾病的危险因素,严重威胁人类健康和生命。通常认为肥胖的发生是遗传因素与环境因素相互作用的结果。在构建饮食性肥胖模型过程中,动物常出现两种截然不同的表型,即肥胖易感和肥胖抵抗。既往研究主要基于体重、体成分、物质与能量代谢、行为学（如摄食偏好）等探讨肥胖易感型和肥胖抵抗型表型差异,然而其内部调控机制,仍没有较为明确而系统的阐述。本文在综述表型特征的基础上,从脂质代谢、胃肠道激素水平和肠道炎症、肠道微生物群和肠-脑轴信号通路、下丘脑-垂体-甲状腺轴、下丘脑弓状核食欲调节系统功能改变以及表观遗传学等方面探讨高脂饮食诱导肥胖表型差异的可能机制。     

Slower gastric emptying in high-fat diet induced obese rats is associated with attenuated plasma ghrelin and elevated plasma leptin and cholecystokinin concentrations

Gastrointestinal (GI) motility and gut hormones have been considered to be involved in the development and maintenance of obesity. Our aim was to assess the relationships between gastric emptying (GE), GI transit and gut hormones and leptin concentrations in diet-induced obese rat model. Male 6-week-old Sprague-Dawley rats were fed with a high-fat (HF) diet for 8weeks to generate diet-induced obesity (DIO) and diet resistant (DR) rats. GE, GI transit and plasma ghrelin, cholecystokinin (CCK), PYY and leptin concentrations were determined in DIO, DR and control (CON) rats. The DIO rats had slower GE, higher plasma leptin and CCK concentrations, and lower plasma ghrelin concentration compared with CON and DR rats. GE was correlated with plasma ghrelin (r=0.402, P=0.028), CCK (r=-0.518, P=0.003) and leptin concentration (r=-0.514, P=0.004). The slower GE, which can be considered as an adaptive response aimed at HF diet induced obesity, may be mediated by changes of plasma ghrelin, CCK and leptin concentrations.     

肥胖大鼠模型的建立及其脂代谢相关分子机制研究

目的建立饮食诱导的肥胖(diet-induced obesity,DIO)大鼠模型并初步探讨其发病的分子机制。方法用脂肪含量30%的高脂饲料饲喂雄性SD大鼠25周,观察大鼠体重、Lee’s指数、肝组织病理改变,检测大鼠空腹血糖及空腹血清胰岛素水平,并通过real-time PCR,检测成模大鼠肝脏中乙酰辅酶A羧化酶(ACC)、脂肪酸合酶(FAS)、激素敏感酯酶(HSL)以及固醇调节元件结合蛋白-1c(SREBP-1c)的表达变化。结果高脂饲料饲喂6周后,DIO组大鼠体重、Lee’s指数均显著增加;25周后肝脏脂肪异常蓄积,出现中重度脂肪肝,空腹血糖及胰岛素水平显著升高,出现明显的胰岛素抵抗。肝脏中ACC、FAS和HSL表达显著增加,SREBP-1c表达水平达到正常组的2.56倍,两组间差异极其显著。结论成功建立了DIO大鼠模型,通过检测脂代谢相关基因的表达水平,初步阐释了营养性肥胖的发生与脂代谢变化之间的关系,SREBP-1c,ACC,FAS和HSL参与了DIO的形成,从而初步揭示了脂代谢变化与营养性肥胖的发生的关系。     

Vaspin gene in rat adipose tissue: relation to obesity-induced insulin resistance

Visceral adipose fat has been claimed to be the link between obesity and insulin resistance through the released adipokines. This study aimed to assess the expression of vaspin as one of the recent adipokines in rats abdominal subcutaneous and visceral fat in diet-induced obese (DIO) and in DIO performing 3 weeks swimming exercise (DIO + EXE) compared to control and control + exercise (C + EXE) groups. Vaspin mRNA and protein expression assessed using RT-PCR and Western blotting analysis revealed vaspin expression in DIO and DIO + EXE but not in controls groups. In DIO group, visceral vaspin expression was higher than in that of subcutaneous fat and was positively correlated with body weight. Upregulation of visceral vaspin expression in DIO was concomitant with the development of insulin resistance (increase in fasting serum insulin and HOMA-IR) and rise in serum leptin level. Unchanged visceral vaspin mRNA in DIO + EXE rats, with significant improvements of insulin resistance parameters and serum leptin compared to DIO group was found. In conclusion, increased visceral vaspin expression in obesity was associated with insulin resistance. Further investigations into the molecular links between vaspin and obesity may unravel innovative therapeutic strategies in people affected by obesity-linked insulin resistance, metabolic syndrome, and type 2 diabetes.     

Ontogeny of diet-induced obesity in selectively bred Sprague-Dawley rats

Outbred Sprague-Dawley rats selectively bred for their propensity to develop diet-induced obesity (DIO) become heavier on low-fat diet than those bred to be diet resistant (DR) beginning at approximately 5 wk of age. Here we assessed the development of metabolic and neural functions for insights into the origins of their greater weight gain. From week 5 to week 10, chow-fed DIO rats gained 15% more body weight and ate approximately 14% more calories but had only slightly greater adiposity and plasma leptin than DR rats. From day 3 through week 10, DIO and DR rats had similar mRNA expression of arcuate nucleus neuropeptide Y, proopiomelanocortin, agouti-related peptide, and all splice variants of the leptin receptor (OB-R). When fed a high-energy (HE; 31% fat) diet, 7-wk-old DIO rats had a 240% increase in plasma leptin levels after only 3 days. Despite this early leptin rise, they maintained a persistent hyperphagia and became more obese than chow-fed DIO rats and DR rats fed chow or HE diet. Their failure to reduce caloric intake, despite high levels of leptin, suggests that selectively bred DIO rats might have reduced leptin sensitivity similar to that seen in the outbred DIO parent strain.     

Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats

In rats selectively bred to develop diet-induced obesity (DIO) or to be diet-resistant (DR), DIO maternal obesity selectively enhances the development of obesity and insulin resistance in their adult offspring. We postulated that the interaction between genetic predisposition and factors in the maternal environment alter the development of hypothalamic peptide systems involved in energy homeostasis regulation. Maternal obesity in the current studies led to increased body and fat pad weights and higher leptin and insulin levels in postnatal day 16 offspring of both DIO and DR dams. However, by 6 wk of age, most of these intergroup differences disappeared and offspring of obese DIO dams had unexpected increases in arcuate nucleus leptin receptor mRNA, peripheral insulin sensitivity, diet- and leptin-induced brown adipose temperature increase and 24-h anorectic response compared with offspring of lean DIO, but not lean DR dams. On the other hand, while offspring of obese DIO dams did have the highest ventromedial nucleus melanocortin-4 receptor expression, their anorectic and brown adipose thermogenic responses to the melanocortin agonist, Melanotan II (MTII), did not differ from those of offspring of lean DR or DIO dams. Thus, during their rapid growth phase, juvenile offspring of obese DIO dams have alterations in their hypothalamic systems regulating energy homeostasis, which ameliorates their genetic and perinatally determined predisposition toward leptin resistance. Because they later go onto become more obese, it is possible that interventions during this time period might prevent the subsequent development of obesity.