人类皮下和网膜脂肪组织脂肪细胞因子的表达

目的 探讨脂肪细胞因子在成人皮下和网膜脂肪组织中的表达水平。方法 应用即刻定量PCR方法测定16例成人皮下和网膜脂肪组织中瘦素、脂联素、肿瘤坏死因子α（TNF-α）和抵抗素的表达水平。结果 正常体重组和超重组皮下脂肪组织瘦素mRNA水平均明显高于网膜组织（P〈0．01）;正常组网膜脂肪组织脂联素mRNA水平较皮下组织有升高趋势（P=0．07）;TNF-α和抵抗素mRNA表达水平低下且无显著部位差异。无论皮下或网膜脂肪组织瘦素表达水平均与体重指数（BMI）成正相关（皮下：r=0．68,P〈0．01;网膜：r=0．71,P〈0．01））,而网膜脂肪组织脂联素表达与BMI呈明显负相关（r=-0．60,P〈0．05）。结论 基因编码的一些细胞因子在脂肪组织中的表达呈部位特征,肥胖时皮下和网膜脂肪组织瘦素过度表达,而内脏脂肪组织脂联素表达下调,这可能是肥胖相关的胰岛素抵抗发生的潜在危险因素。     

重症急性胰腺炎大鼠单核细胞趋化蛋白1的表达

目的 探讨单核细胞趋化蛋白1（MCP-1）在重症急性胰腺炎（SAP）发病及其相关的急性肺损害（ALI）中的作用。方法 48只雄性SD大鼠随机分为SAP组和手术对照组,采用向胆胰管逆行注射5％牛磺胆酸钠建立大鼠SAP模型,术后1、3、6和12h分别观察血清淀粉酶,胰腺和肺组织病理组织学改变,酶联免疫固相吸附试验（EUSA）法测定血清中MCP-1水平,免疫组织化学法和逆转录-聚合酶链反应（RT-PCR）法检测胰腺和肺组织中MCP-1蛋白和MCP-1 mRNA的表达。结果 SAP组术后6、12h血清中MCP-1水平高于手术对照组（P〈0．05）,胰腺组织和肺组织中的MCP-1蛋白和MCP-1 mRNA的表达亦高于手术对照组（P〈0．05或P〈0．01）,且MCP-1的表达与胰腺和肺组织的病理学改变呈正相关。结论 MCP～1可能在SAP发病及其相关的ALI中起了重要的作用。     

独一味对内毒素血症BALB／c小鼠血清细胞因子的影响

目的检测独一味预处理对内毒素血症BALB／C小鼠血清细胞因子水平的影响,初步探讨独一味对炎症的调节机制。方法用独一味浸膏液对雄性BALB／c小鼠进行灌胃预处理,5d后给予内毒素促使内毒素血症的发生,6h后动物断头取血,制备血清样品,利用LiquiChip系统检测血清细胞因子水平。结果细胞因子检测发现,非致死性内毒素血症6h时血清细胞因子普遍增高,为正常水平的数倍到数百倍（P〈0．01）。给予独一味处理可以改变内毒素血症细胞因子的血清水平,使血清MCP-1约下降20％（P〈0．01）,血清TNFa约下降40％（P〈0．01）,使血清IL-1β约上升1倍（P〈0．01）,血清IL-4上升了37％（P〈0．01）,血清IL-10约上升20％（P〈0．01）,独一味对血清IL-6水平没有明显影响（P〉0．05）。结论独一味对内毒素血症不同细胞因子的调节不同,具有选择性和多样性。其提高了抗炎细胞因子的水平,减少了部分促炎因子的表达,避免发生过激的炎症反应,保护机体组织,且同时还提高IL-1等促炎细胞因子的表达,增强机体的天然免疫机制。     

急性脑梗死患者血清白细胞介素-6、白细胞介素-8及脂联素水平变化及意义

目的探讨急性脑梗死（ACI）患者的血清IL-6、IL-8及脂联素水平变化。方法采用ELISA法检测98例急性脑梗死患者血清白细胞介素6（IL-6）、白细胞介素8（IL-8）及脂联素含量,并与98例健康对照组比较分析。结果急性脑梗死组血清IL-6、IL-8水平明显升高,而脂联素水平则显著降低,两组差异均有统计学意义（均P〈0．01）;血清IL-6和IL-8水平随梗死体积增大和神经功能缺损程度加重而升高,脂联素水平则降低;血清脂联素水平与血清IL-6、IL-8水平呈显著负相关（r=-0．733,r=-0．715;均P〈0．05）,IL-6与IL-8呈显著正相关（r=0．830,P〈0．01）。结论血清IL-6、IL-8及脂联素水平反映了病情轻重及神经功能缺损程度,与脑梗死的临床变化有较密切关系。     

脂联素对高糖环境下hRPE活性及VEGF mRNA表达的影响

目的观察脂联素对高糖环境下人视网膜色素上皮细胞（hRPE）活性及血管内生长因子（VEGF）mRNA表达的影响,探讨脂联素对糖尿病视网膜病变（DR）可能具有的保护机制。方法①将hRPE随机分为对照组、高糖组、甘露醇组、脂联素组,培养48h后MTT法测定细胞活性。②再将hRPE分为对照组、高糖组、脂联素组,分别培养24、48、72h后用荧光定量PCR测定VEGF mRNA的表达。结果与对照组相比,甘露醇组细胞活性无明显改变（P〉0．05）,高糖组明显降低（P〈0．01）;加入脂联素后,细胞活性显著升高（P=〈0．01）。高糖组与对照组相比,mRNA表达明显上调,加入脂联素后表达呈时间依赖性下调,差异有统计学意义（P〈0．01）。结论脂联素可以促进hRPE增殖,下调VEGF mRNA的表达。提示脂联素可通过下调hRPE VEGF mRNA的表达来抑制DR中病理性新生血管的形成。     

硫酸镁对杂种犬急性肺动脉高压模型抗炎机制研究

目的探讨硫酸镁对急性肺栓塞肺动脉高压的影响及其抗炎机制。方法18只杂种犬,随机分为空白组、对照组及硫酸镁2．0mm／kg组（MgSO4 2．0组）,每组6只。其中空白组不给于任何处理,对照组只给予处理造成急性肺动脉高压,MgSO4 2．0组造成急性肺动脉高压稳定30min后,以2．0mm／kg 10min内静脉滴注给予硫酸镁;肺动脉、股动脉插管检测平均肺动脉压（MPAP）、体循环平均动脉压（MAP）,应用酶联免疫吸附以及放免法分别测定血清中白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）,westernblot测定肺组织中MCP—l蛋白表达。结果对照组MPAP较空白组显著升高,MgS042．0组MPAP较对照组显著下降（P〈0．05或〈0．01）;对照组MAP较空白组显著下降,MgSO4 2．0组MAP较对照组显著升高（P〈0．05或〈0．01）;对照组血清中TNF-α以及IL-6空白组显著升高,MgSO4 2．0组TNF-α以及IL-6较对照组显著下降（P〈0．05或〈0．01）;对照组MCP-1蛋白表达较空白组显著升高,MgSO4 2．0组MCP-1蛋白表达较对照组显著下降（P〈0．05或〈0．01）。结论硫酸镁可显著降低肺动脉高压,这可能与其抑制肺组织MCP-1表达,降低TNF-α以及IL-6,从而抑制炎性反应增强有关。     

脂联素和原发性高血压患者脉压指数相关性的研究

目的分析血浆脂联素（adiponectin）与原发性高血压（essential hypertension,EH）患者的收缩压（SBP）、舒张压（DBP）、脉压（pulse pressure,PP）、平均动脉压（MAP）和脉压指数（pulse pressure index,PPI）之间的相关性。方法56例新发现且未经过治疗的轻、中度EH患者和54例正常人,记录年龄、性别,测定体重指数（BMI）、空腹血糖（FPG）、血脂谱及血压,放射免疫分析法测定空腹胰岛素（FINS）、血浆脂联素水平。结果EH组血浆脂联素水平较对照组显著降低（P〈0．05）。Pearson相关分析显示：EH组血浆脂联素水平与SBP（P〈0．01）、PP（P〈0．05）、MAP（P〈0．05）和PPI（P〈0．01）呈显著负相关。对照组血浆脂联素水平与SBP、PP、MAP、PPI不具有相关性。结论原发性高血压患者伴有低脂联素血症,异常升高的血压可能是低脂联素血症的原因之一。     

辛伐他汀对代谢综合征患者炎性反应及胰岛素抵抗的影响

目的探讨辛伐他汀对代谢综合征患者炎性反应及胰岛素抵抗的影响。方法48例代谢综合征患者按入院单双号随机分为辛伐他汀组及对照组,两组均给予常规治疗,辛伐他汀组每天加用辛伐他汀40mg,1次／d,治疗8局,观察两组治疗前后血浆超敏C反应蛋白（hsCRP）及脂联素水平,并计算胰岛素抵抗指数。结果辛伐他汀组治疗后hsCRP水平较治疗前明显降低（P〈0．05）,而脂联素水平及胰岛素抵抗指数治疗前后无明显差异（均P〉0．05）;辛伐他汀组治疗后低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及总胆固醇水平较治疗前差异均有统计学意义（均P〈0．05）。结论辛代他汀可减轻代谢综合征患者的炎性反应,对胰岛素抵抗未见明显影响。     

持续性皮下胰岛素输注对初诊2型糖尿病患者脂联素水平的影响

目的探讨持续性皮下胰岛素输注（Continuous Subcutaneous Insulin Infusion,CSII）注射对初诊2型糖尿病患者脂联素水平的影响。方法将42例初诊2型糖尿病患者随机分为治疗组和对照组,治疗组采用CSII,对照组仅皮下胰岛素注射,2组治疗前及治疗后2周后,采用ELISA进行脂联素水平及HOMA指数、血脂水平评估。结果治疗组2周后,对照组及治疗组与治疗前对比脂联素均显著升高,治疗组比较对照组游离脂肪酸下降更明显,差异有统计学意义（P〈0．01）。脂联素水平与HOMA指数（P〈0．01）、游离脂肪酸（P〈0．05）、三酰甘油水平（P〈0．05）显著相关,与胆固醇、高密度脂蛋白、低密度脂蛋白无关（P〉0．05）。结论持续性皮下胰岛素输注均能快速有效的提高初诊2型糖尿病患者脂联素水平。     

替米沙坦对糖尿病合并高血压患者脂联素及胰岛素抵抗的影响

目的：观察替米沙坦治疗2型糖尿病伴高血压患者后血清脂联素的变化及其对胰岛素抵抗的影响。方法：42例2型糖尿病伴高血压患者，口服替米沙坦80～160mg，qd，共12周，观察治疗前和治疗后的血清脂联素、肿瘤坏死因子（TNF—α）浓度，并观察血压、血脂和胰岛素抵抗指数（IRT）水平。结果：替米沙坦治疗后收缩压和舒张压明显下降（P〈0．05），血清脂联素浓度明显升高（P〈0．05），TNF—α浓度明显下降（P〈0．05）；IRI下降（P〈0．05）。结论：替米沙坦在升高血清脂联素浓度和降低TNF-α浓度的同时，具有改善胰岛素抵抗的作用。     

胰腺癌细胞可溶性分泌物对小鼠脂代谢的影响

目的 探讨胰腺癌细胞可溶性分泌物对体内脂肪代谢的影响。方法 利用无血清培养基培养胰腺癌 Panc-1、MiaPaCa-2、BxPC-3细胞24 h后留取上清制得胰腺癌细胞条件培养基。全实验包括两个子实验,实验A将 37只BALB/c小鼠随机分为对照组（n=14）,Panc-1组（n=10）,MiaPaC-2组（n=6）和BxPC-3组（n=7）,分别注射正常 DMEM培养基和3种胰腺癌细胞（Panc-1,MiaPaCa-2,BxPC-3）条件培养基,每组小鼠连续7 d接受培养基的皮下注 射,每日2次。监测每只小鼠进食量及体质量,检测血浆葡萄糖、三酰甘油含量和肝脏中糖原含量,酶联免疫吸附法 （ELISA）测定血浆胰岛素水平,小鼠的腹股沟脂肪垫（BAT）、附睾脂肪垫（WAT）予以称质量,Western blot检测脂肪中 脂肪甘油三酯脂肪酶（ATGL）蛋白表达水平。实验B将30只BALB/c小鼠随机分为对照组（n=10）、1/2 M组（n=10）、M 组（n=10）,将正常DMEM培养基和不同剂量的MiaPaCa-2细胞条件培养基注射入对应组别小鼠体内,余处理与实验 A相同。结果 实验A中,小鼠进食量及体质量初期均下降,之后回升并趋于稳定,与对照组相比,MiaPaCa-2组和 BxPC-3组血浆胰岛素、血糖水平升高（P＜0.05）,肝糖原、三酰甘油水平下降（P＜0.05）,BAT和WAT质量增加（P＜ 0.05）,Panc-1组仅三酰甘油水平下降（P＜0.05）,3个胰腺癌细胞条件培养基注射组脂肪组织内ATGL表达水平均下 降（P＜0.05）;实验 B 中,与对照组相比,M 组血浆胰岛素和葡萄糖上升（P＜0.05）,肝糖原和三酰甘油均下降（P＜ 0.05）,BAT 和 WAT 质量增加（P＜0.05）,ATGL 表达水平下降（P＜0.05）,1/2 M 组仅胰岛素水平和脂肪垫质量上升 （P＜0.05）。结论 注射胰腺癌细胞条件培养基可造成小鼠体内脂肪代谢失衡,出现胰岛素抵抗、脂肪储存加强和脂 肪分解减弱的现象。     

Establishment and pathophysiological characterization of type 2 diabetic mouse model produced by streptozotocin and nicotinamide

This study was performed in order to establish a mouse model that represents the non-obese type 2 diabetes reflecting a majority of diabetic patients among Asian races and to show its pathophysiological profiles. Streptozotocin (STZ) was administered to C57BL/6J mice with or without nicotinamide (120 or 240 mg/kg, STZ/NA120 or STZ/NA240), twice with an interval of 2 d, and plasma glucose concentration, body weight, water intake, insulin contents and insulin signal-related proteins were monitored. STZ-induced hyperglycemia (fasting and non-fasting), body weight loss and polyposia were significantly depressed by NA dose-dependently. In STZ/NA120 and STZ/NA240 mice, pancreatic insulin content was retained by 28 and 43% of normal control (10.5+/-0.93 muU/ml), respectively, and histological damage of pancreatic beta cells was also less severe than that observed in STZ mice. When given the calorie-controlled high fat diet, the STZ/NA mice caused hyperlipidemia, and significantly increased insulin resistance. These observations suggest that the combined administration of STZ and NA causes partial depletion of pancreatic insulin and that the high fat constituents lead to insulin resistance in this model. The present mouse model, therefore, well exhibits the recent diabetic pathophysiological characteristics of a majority of Asian patients.     

C-terminal mini-PEGylation of glucose-dependent insulinotropic polypeptide exhibits metabolic stability and improved glucose homeostasis in dietary-induced diabetes

Glucose-dependent insulinotropic polypeptide has been proposed as a potential therapeutic for type 2 diabetes, however, efforts to bring forward this drug have been hindered due to its short circulating half-life. We have adopted a novel strategy to increase potency and prolong GIP action through C-terminal mini-PEGylation (GIP[mPEG]). In contrast to GIP, GIP[mPEG] was resistant to dipeptidylpeptidase-IV (DPP-IV) up to and including 24h. Both GIP[mPEG] and GIP concentration-dependently stimulated cAMP production (EC50 6.6 and 0.7 nM, respectively) and insulin secretion (p < 0.01 to p < 0.001) in pancreatic BRIN-BD11 cells. Acute injection of GIP[mPEG] together with glucose to high fat fed mice significantly lowered plasma glucose (p < 0.05) and increased plasma insulin responses (p < 0.05). Furthermore, GIP[mPEG] markedly lowered plasma glucose when administered 4-24h prior to a glucose load (p < 0.05). Daily administration of GIP[mPEG] for 20 days in high fat mice did not alter body weight, food intake or non-fasting plasma insulin, however, non-fasting plasma glucose concentrations were significantly lowered (p < 0.05). Moreover, glucose tolerance was significantly improved (p < 0.05) together with glucose-mediated plasma insulin responses (p < 0.05). Insulin sensitivity, pancreatic insulin content, triglyceride and adiponectin levels were not changed. In summary, these data demonstrate that C-terminal mini-PEGylation of GIP is a useful strategy to prolong metabolic stability and improve biological action thus representing a novel therapeutic option for type 2 diabetes.     

Obesity decreases the oxidant stress induced by tobacco smoke in a rat model

Obesity and emphysema are associated with low-grade systemic inflammation and oxidant stress. Assuming that the oxidant stress induced by emphysema would be decreased by obesity, we analyzed the oxidant/antioxidant state in a rat model combining both diseases simultaneously. Obesity was induced using sucrose, while emphysema by exposure to tobacco smoke. End-points evaluated were: body weight, abdominal fat, plasma dyslipidemia and malondialdehyde (MDA), insulin and glucose AUC, activities of Mn-superoxide dismutase (Mn-SOD), glutathione reductase (GR), glutathione transferase (GST) and glutathione peroxidase (GPx); lung MnSOD and 3-nitrotyrosine (3-NT) immunostaining, and expression of αV and β6 integrin subunits. In rats with obesity, the body weight, abdominal fat, plasma triglyceride levels, glucose AUC, insulin levels, GST activity, and αV and β6 integrin expressions were amplified. The rats with emphysema had lower values of body weight, abdominal fat, plasma insulin, triglycerides and glucose AUC but higher values of plasma MDA, GPx activity, and the lung expression of the αV and β6 integrins. The combination of obesity and emphysema compared to either condition alone led to diminished body weight, abdominal fat, plasma insulin MDA levels, GPx and GST activities, and αV and β6 integrin expressions; these parameters were all previously increased by obesity. Immunostaining for MnSOD augmented in all experimental groups, but the staining for 3-NT only increased in rats treated with tobacco alone or combined with sucrose. Results showed that obesity reduces oxidant stress and integrin expression, increasing antioxidant enzyme activities; these changes seem to partly contribute to a protective mechanism of obesity against emphysema development.     

Rapamycin impairs HPD-induced beneficial effects on glucose homeostasis

Background and Purpose

Rapamycin, which is used clinically to treat graft rejection, has also been proposed to have an effect on metabolic syndrome; however, very little information is available on its effects in lean animals/humans. The purpose of this study was to characterize further the effects of the continuous use of rapamycin on glucose homeostasis in lean C57BL6/J mice.

Experimental Approach

Mice were fed a high-protein diet (HPD) for 12 weeks to develop a lean model and then were treated daily with rapamycin for 5 weeks while remaining on a HPD. Metabolic parameters, endocrine profiles, glucose tolerance tests, insulin sensitivity index, the expression of the glucose transporter GLUT4 and chromium distribution were measured in vivo.

Key Results

Lower body weight gain as well as a decreased caloric intake, fat pads, fatty liver scores, adipocyte size and glucose tolerance test values were observed in HPD-fed mice compared with mice fed a high-fat or standard diet. Despite these beneficial effects, rapamycin-treated lean mice showed greater glucose intolerance, reduced insulin sensitivity, lower muscle GLUT4 expression and changes in chromium levels in tissues even with high insulin levels.

Conclusion and Implications

Our findings demonstrate that continuous rapamycin administration may lead to the development of diabetes syndrome, as it was found to induce hyperglycaemia and glucose intolerance in a lean animal model.     

Long‐term Administration of Rapamycin Reduces Adiposity,but Impairs Glucose Tolerance in High‐Fat Diet‐fed KK/HlJ Mice

Abstract: Rapamycin is an immunosuppressant drug used to prevent organ rejection in transplant patients. In this study, we investigated the metabolic effects of rapamycin in an obese animal model, KK/HlJ mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle for 42 days on a high‐fat diet. Treated mice lost body weight and adiposity, reduced weight gain and retroperitoneal and epididymal fat pads/body weight, decreased serum leptin and plasma triglyceride levels and had lower liver fat concentration. However, treated mice had higher serum insulin levels and food intake. Dissection of rapamycin‐treated mice revealed a marked reduction in fatty liver scores and fat cell size in retroperitoneal and epididymal adipocytes. Moreover, Western blot analysis revealed that rapamycin treatment resulted in decreasing adipophilin expression, as a marker of lipid accumulation, and reducing phosphorylation of mTOR downstream targets S6K1 compared to control group. Unfortunately, rapamycin‐treated animals showed a marked decline in glucose tolerance as judged by the 180‐min. area under the curve for plasma glucose levels, paralleled by increased generation of plasma reactive oxygen species. These results suggest that continual rapamycin administration may help to prevent diet‐induced obesity, while prolonged use of rapamycin may exacerbate glucose intolerance.     

Subacute inhalation exposure to ozone induces systemic inflammation but not insulin resistance in a diabetic mouse model

Epidemiological studies suggest that diabetics may be more susceptible to the adverse health effects from exposure to high ambient concentrations of ozone, the primary oxidant gas in photochemical smog. While increased morbidity and mortality from ozone inhalation has been linked to disruption of normal cardiovascular and airway functions, potential effects on glucose and insulin homeostasis are not understood. We tested the hypothesis that ozone exposure would worsen metabolic homeostasis in KKAy mice, a genetic diabetic animal model. Male KKAy mice were exposed to 0.5?ppm ozone for 13 consecutive weekdays, and then assessed for airway, adipose and systemic inflammation, glucose homeostasis, and insulin signaling. Ozone exposure increased plasma TNFα, as well as expression of VCAM-1, iNOS and IL-6 in both pulmonary and adipose tissues. Pro-inflammatory CD11b⁺Gr-1^lo7/4^hi macrophages were increased by 200% in adipose tissue, but unchanged in blood. Interestingly, glucose levels were not significantly different in the insulin tolerance test between air- and ozone-exposed mice, whereas fasting insulin levels and HOMA-IR in ozone-exposed animals were significantly reduced. These changes were accompanied by increased insulin signaling in skeletal muscle and liver, but not adipose tissues. Ozone also caused decrease in body weight and plasma leptin. Our results show that in addition to marked local and systemic inflammation, ozone increases insulin sensitivity that may be related to weight loss/leptin sensitization-dependent mechanisms in KKAy mice, warranting further study on the role of hyperglycemia in mediating cardiometabolic effects of ozone inhalation.     

Markedly reduced white adipose tissue and increased insulin sensitivity in adcyap1-deficient mice

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide implicated in several metabolic functions, including insulin secretion and sympathoadrenal activation. To clarify the roles of PACAP in maintenance of whole-body glucose and lipid homeostasis, the impact of the deletion of PACAP on glucose homeostasis, body weight, and adipose tissue mass was examined by comparing mice lacking the Adcyap1 gene encoding PACAP (Adcyap1(-/-)) with wild-type littermate controls. Adcyap1(-/-) mice showed significant hypoinsulinemia, although being normoglycemic, and lower body weight as well as reduced food intake. They also showed greatly reduced white adipose tissue mass, in which the mRNA expression of adipocyte fatty acid-binding protein (aP2), a marker of adipocyte differentiation, was decreased. Glucose and insulin tolerance tests revealed increased insulin sensitivity in Adcyap1(-/-) mice. In accordance with these observations, plasma levels of resistin, an adipocytokine implicated in insulin resistance, were decreased in Adcyap1(-/-) mice. After a high-fat dietary challenge for six weeks, Adcyap1(-/-) mice still showed lower body weights and increased insulin sensitivity. These results indicate the crucial roles of PACAP in energy metabolism, including lipid metabolism, and in the regulation of body weight, raising the possibility that the PACAP-signaling pathway that favors energy storage could be a therapeutic target for obesity.     

Effect of ouabain on insulin secretion in the anesthetized dog

The effect of ouabain on insulin secretion has been studied in the anesthetized dog. Blood glucose, plasma free fatty acids and plasma amino nitrogen were determined simultaneously. When infused at a dose of 1 μg/kg/min, ouabain significantly reduces blood glucose and plasma free fatty acid levels and increases plasma amino nitrogen. Plasma insulin concentrations are significantly increased in both arterial and pancreaticoduodenal venous blood. The pancreaticoduodenal vein blood flow is not significantly modified. Calculated pancreatic insulin production is markedly increased during ouabain infusion. These findings were confirmed using “one shot” injections of ouabain. The mechanism of the marked in vivo effect of ouabain on insulin production is discussed.     

Dietary corosolic acid ameliorates obesity and hepatic steatosis in KK-Ay mice

Corosolic acid (CRA), a constituent of Banaba leaves, has been reported to exert anti-hypertension, anti-hyperinsulinemia, anti-hyperglycemia, and anti-hyperlipidemia effects as well as to induce anti-inflammatory and anti-oxidative activities. The aim of this study was to investigate the inhibitory effects of CRA on the development of obesity and hepatic steatosis in KK-Ay mice, a genetically obese mouse model. Six-week-old KK-Ay mice were fed a high fat diet for 9 weeks with or without 0.023% CRA. Nine-week CRA treatment resulted in 10% lower body weight and 15% lower total fat (visceral plus subcutaneous fat) mass than in control mice. CRA treatment reduced fasting plasma levels of glucose, insulin, and triglyceride by 23%, 41%, and 22%, respectively. The improved insulin sensitivity in CRA-treated mice may be due on part to the increased plasma adiponectin and white adipose tissue (WAT) AdipoR1 levels. In addition, CRA treatment increased the expression of peroxisome proliferator-activated receptor (PPAR) alpha in liver and PPAR gamma in WAT. This is the first study to show that CRA treatment can contribute to reduced body weight and amelioration of hepatic steatosis in mice fed a high fat diet, due in part to increased expression of PPAR alpha in liver and PPAR gamma in WAT.