白藜芦醇对KKAy 小鼠的胰岛素敏感性影响及机制

目的：观察白藜芦醇对胰岛素抵抗小鼠(KKAy)胰岛素敏感性的影响,并探讨其机制。方法：将36 只8周龄KKAy 小鼠分成3 组,其中两组KKAy 小鼠分别饲喂添加白藜芦醇的AIN93G 饲料(2g/kg 饲料 或4g/kg 饲料),另一组KKAy 小鼠为模型组,另外以12 只同周龄C57BL/6J 小鼠为对照。观察白藜芦醇对小鼠血糖、血清胰岛素 水平、葡萄糖耐量、胰岛素耐量等的影响;Western blot 实验检测不同组小鼠肝脏中沉默信息调节因子1(silent information regulator 1,sirt-1)蛋白表达及胰岛素受体底物1(insulin receptor substrate 1,IRS-1)的磷酸化水平。结 果：白藜芦醇干预可以增强KKAy 小鼠胰岛素敏感性,改善胰岛素耐量和葡萄糖耐量;肝脏中sirt-1 的表达和IRS-1 的磷酸化水平均升高。结论：白藜芦醇可以改善小鼠胰岛素抵抗及糖耐量异常,这可能与白藜芦醇提高肝脏中sirt-1 的表达,从而激活胰岛素信号通路相关蛋白有关。     

新橙皮苷对3T3-L1前脂肪细胞分化的影响及其作用机制

为探讨新橙皮苷对脂肪细胞脂肪形成的影响及其作用机制,采用MTS法检测新橙皮苷对3T3-L1前脂肪细胞的细胞活力的影响,确定新橙皮苷的作用浓度后,油红O染色法和分光光度法测定3T3-L1脂肪细胞的分化及胞内甘油三酯的含量,RT-PCR测定脂肪形成相关基因CCAAT增强子结合蛋白α（CCAAT/enhancer binding proteinα,C/EBPα）和过氧化物酶体增殖激活受体γ（Peroxisome proliferators-activated receptorγ,PPARγ）mRNA表达,Western蛋白印迹法检测蛋白激酶B（Protein kinase B,PKB/Akt）、糖原合成酶激酶3β（Glycogen synthase kinase3β,GSK3β）和糖原合成酶（Glycogen synthase,GS）的磷酸化水平;利用GSK3β选择性的抑制剂LiCl作用3T3-L1脂肪细胞后,检测新橙皮苷对3T3-L1细胞分化、胞内甘油三酯含量、C/EBPα、PPARγ及aP2蛋白表达的影响。结果表明,新橙皮苷能极显著抑制脂肪细胞分化和胞内甘油三酯的形成（P<0.01）,激活Akt信号通路,促进p-Akt和p-GSK3β水平增加,极显著抑制C/EBPα、PPARγ、aP2 mRNA和蛋白表达（P<0.01）。新橙皮苷的这些影响部分地被GSK3β抑制剂LiCl所抑制（P<0.01）。新橙皮苷能够通过激活Akt/GSK3β信号通路抑制脂肪细胞分化。     

板栗壳色素通过AMPK信号通路改善肥胖小鼠的脂代谢紊乱

目的:探讨板栗壳色素(CSP)对肥胖小鼠脂代谢紊乱的改善作用及其分子机制。方法:将雄性C57BL/6J小鼠分为正常饮食(N)组、高脂饮食(HFD)组、高脂饮食+20 mg/kg CSP(HFD-L)组、高脂饮食+50 mg/kg CSP(HFD-H)组、高脂饮食+20 mg/kg儿茶素(HFD-C)组,每周测量小鼠体质量和进食量,14周后检测小鼠肝脏和附睾脂肪质量、血清血脂水平,进行脂肪与肝脏形态学分析,检测肝脏中脂肪代谢关键蛋白的表达等。结果:与HFD组相比,HFD-L和HFD-H组小鼠体质量增长量分别降低28.67%和39.16%;附睾脂肪质量分别降低23.63%和42.80%;CSP能减少进食量、脂肪细胞的扩大和肝脏脂肪的积累,降低血清TG、TC、LDL-C、ALT和AST水平,升高HDL-C,显著升高小鼠肝脏组织中p-AMPK/AMPK、p-ACC/ACC、PPARα的表达量,显著降低SREBP-1c和HMGCR的表达量,且作用效果比单一儿茶素效果好。结论:板栗壳色素具有改善肥胖小鼠脂代谢的作用,此作用与激活AMPK信号通路相关。     

樱桃李果实提取物对小鼠高脂膳食诱导肥胖的预防作用

探讨樱桃李果实提取物对小鼠高脂膳食诱导肥胖的预防作用。通过水提法获得果实粗提物,采用福林酚法测定多酚含量,DPPH法测定体外抗氧化活性。小鼠被饲喂高脂饲料的同时,喂食樱桃李果实提取物,每周测定小鼠体重,10周后测定小鼠血清、肝脏中的有关生化指标,采用荧光定量PCR测定肝脏脂代谢相关基因的表达。试验结果表明,樱桃李果实提取物能够显著降低高脂膳食诱导肥胖小鼠体重,降低血清及肝脏中甘油三酯(TG)、总胆固醇(T-CHO)含量,提高血清中超氧化物歧化酶(SOD)含量,降低血清碱性磷酸酶(AKP)、谷草转氨酶(AST/GOT)、谷丙转氨酶(ALT/GPT)含量;樱桃李果实提取物显著下调脂代谢相关转录调控因子过氧化物酶体增殖物激活受体(PPARγ)、CCAAT/增强子结合蛋白α(C/EBPα)、脂肪生成转录因子甾醇调节元件结合蛋白1c(SREBP-1c)、脂肪酸合成酶(FAS)的表达。结论:樱桃李果实提取物对高脂膳食诱导的小鼠肥胖具有预防作用,能提高机体的抗氧化活性,对其肝脏损伤有一定的保护作用。     

玉米黄素调控肥胖小鼠肝脏脂质及能量代谢作用

目的：研究玉米黄素对高脂饮食诱导肥胖小鼠肝脏脂质及能量代谢调控的影响。方法：建立高脂饮食诱导C57BL/6J肥胖小鼠模型,饲喂不同剂量玉米黄素（40和20 mg/kg）干预4周,测定其体重、脂肪和肝脏组织质量;对肝脏组织进行HE染色,并检测肝脏组织中脂质代谢相关因子CCAAT/增强子结合蛋白α（C/EBPα）、固醇调节元件结合蛋白-1c（SREBP1-c）、乙酰辅酶A羧化酶（ACC）和脂肪酸转位酶（CD36）,能量代谢相关因子过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC-1α）、解偶联蛋白1（UCP1）和沉默信息调节因子2同源蛋白1（SIRT1）的基因表达及其对AMP依赖的蛋白激酶（AMPK）信号通路的影响。结果：与高脂模型组相比,玉米黄素干预能够显著降低体重增加量、肝脏组织质量,降低肝脏组织脂代谢相关基因C/EBPα、SREBP1-c、ACC和CD36的表达,增加UCP1基因表达,低剂量组可显著激活AMPK信号通路。结论：玉米黄素可通过激活肝脏组织AMPK信号通路,下调AMPK靶基因C/EBPα、SREBP1-c、ACC和CD36的脂质合成基因表达水平,提高能量代谢UCP1基因水平,抑制肝脏脂质累积,并改善高脂饮食肥胖小鼠的病理状态。     

蕨菜提取物抗肥胖作用及其机制

研究蕨菜对3T3-L1前脂肪细胞分化和高脂饮食诱导C57BL/6J小鼠肥胖的抑制作用,初步探讨其作用机制。培养3T3-L1前脂肪细胞并诱导其分化,油红O染色比色分析蕨菜乙醇提取物(PAE)对其分化程度的影响,Western blot法检测其对脂肪细胞分化转录调控因子(PPARγ、CEBPα、SREBP-1c)与脂质合成相关基因(FAS、ACC)的表达水平。以高脂饮食6周建立C57BL/6J肥胖小鼠模型,将诱导成功的肥胖小鼠分为高脂对照组(HFD)、1%蕨菜乙醇提取物组(HFD+PAE),另设立正常饲料喂养的C57BL/6J小鼠为正常组(ND)。继续喂养8周后测定各组小鼠体质量,评价其脂代谢状况(甘油三酯、胆固醇)及糖代谢情况(血糖、葡萄糖耐量)。结果显示,PAE能显著抑制3T3-L1前脂肪细胞分化,减少细胞中脂质的沉积。PAE显著影响脂肪细胞分化过程中细胞分化转录调控因子PPARγ、CEBPα、SREBP-1c的蛋白表达(P0.05),同时降低脂质合成相关基因FAS、ACC的表达(P0.05)。经过高脂饮食诱导C57BL/6J肥胖小鼠体质量增加,体脂沉积显著,血糖、血脂水平明显高于ND组(P0.05)。PAE干预后,小鼠体质量、甘油三酯、血糖水平均较HFD明显降低(P0.05),葡萄糖耐量也得到显著改善(P0.05)。蕨菜乙醇提取物抑制了3T3-L1脂肪细胞分化,改善了肥胖小鼠体质量,消除了高血脂和高血糖异常,修复了葡萄糖耐量,这一作用可能与其调控脂肪细胞分化转录调控因子和脂质合成相关基因等密切相关。     

过氧物酶体增生激活受体配体及其生物学意义

PPARs是由不同基因编码的核受体,包括3种亚型PPARα、PPARδ和PPARγ,PPARs可与过氧化物酶体增长因子反应元件(PPREs)的特异敏感DNA序列结合,而呈现不同的表达。其中PPARα调节营养物质的代谢,包括调节脂肪酸氧化,糖异生,氨基酸代谢等;PPARδ表达能有效地控制血脂和心血管疾病;PPARγ在脂肪组织中表达,刺激脂肪生成。因此,PPAR成为设计合成糖尿病等不同类型人类代谢紊乱治疗药物的有效靶点。     

表没食子儿茶素没食子酸酯对小鼠非酒精性脂肪肝的干预作用

本文研究了表没食子儿茶素没食子酸酯(EGCG)对小鼠非酒精性脂肪性肝病(NAFLD)的干预作用。应用高脂饲料喂养Apo E-/-小鼠建立NAFLD小鼠模型,研究EGCG对NAFLD小鼠血液和肝组织中糖脂代谢、脂肪酸氧化、氧化应激水平、肝组织结构以及AMPK/SIRT1/SREBP-1c/PPARγ信号通路相关基因表达的影响。结果表明EGCG治疗后肝组织病理学变化明显改善,小鼠体质量、肝质量、肝质量指数较模型组显著降低至110.98%、115.01%,115.64%、136.48%和104.20%、118.70%(p<0.01);血液和肝组织中糖脂代谢、脂肪酸氧化、氧化应激水平改善幅度在11.85%~86.06%之间,与模型组比较具有显著性差异(p<0.05或p<0.01);升高肝组织中AMPKα、SIRT1 mRNA及p-AMPKα、SIRT1蛋白表达幅度在13.21%~75.82%之间,降低肝组织FASN、ACC-1、SREBP-1c、SCD-1、PPARγm RNA和FASN、p-ACC-1、p-SREBP-1c、SCD-1、PPARγ蛋白表达幅度在19.59%~92.07%之间,改善p-AMPKα/AMPKα、p-ACC-1/ACC-1和p-SREBP-1c/SREBP-1c比率在39.20%~93.07%之间,与模型组比较具有显著性差异(p<0.05或p<0.01)。本研究表明EGCG可通过调控AMPK/SIRT1/SREBP-1c/PPARγ信号通路相关基因的表达来改善NAFLD小鼠糖脂代谢、脂肪酸氧化和氧化应激状态。     

辣椒抽提物对缓解小鼠食源性肥胖及调控基因表达的作用

本文比较了二荆条辣椒乙醇抽提物与纯化的辣椒碱对食源性小鼠肥胖的影响,为辣椒抽提物减肥提供理论依据。C57BL/6小鼠被分为四组,分别为对照组、肥胖组(喂食高脂饲料)、辣椒醇提物组(辣椒抽提物+高脂饲料),辣椒碱组(纯化的辣椒碱+高脂饲料)。结果表明,与纯化的辣椒碱相比,辣椒提取物更加有效地抑制体重增加,减少脂肪积累、减小脂肪细胞大小,降低血清、肝脏和粪便甘油三酯(TG)和总胆固醇(TC)的含量。在肝脏和脂肪组织中,脂分解基因(PPARα、CYP7A1、LPL和CPT1α)在肥胖组显著下降,但在辣椒醇提物组和辣椒碱组的显著上调,并且辣椒醇提物组上调程度更高;促脂合成基因PPARγ和C/EBPα在肥胖组、辣椒醇提物组和辣椒碱组都上调,但辣椒醇提物组的上调程度最小。因此,辣椒提取物和辣椒碱都能起到减肥作用,但是辣椒提取物效果更好。     

Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice

Scope: To determine the effect of consumption of a quercetin‐rich diet on obesity and dysregulated hepatic gene expression. Methods and results: C56BL/6J mice were fed for 20 wk on AIN93G (control) or a Western diet high in fat, cholesterol and sucrose, both with or without 0.05% quercetin. Triglyceride levels in plasma, thiobarbituric acid‐reactive substances (oxidative stress marker) and glutathione levels and peroxisome proliferator‐activated receptor α expression in livers of mice fed with the Western diet were all improved after 8 wk feeding with quercetin. After 20 wk, further reductions of visceral and liver fat accumulation and improved hyperglycemia, hyperinsulinemia, dyslipidemia and plasma adiponectin and TNFα levels in these mice fed with quercetin were observed. The expression of hepatic genes related to steatosis, such as peroxisome proliferator‐activated receptor γ and sterol regulatory element‐binding protein‐1c was also normalized by quercetin. In mice fed with the control diet, quercetin did not affect body weight but reduces the plasma TNFα and hepatic thiobarbituric acid‐reactive substance levels. Conclusion: In mice fed with a Western diet, chronic dietary intake of quercetin reduces liver fat accumulation and improves systemic parameters related to metabolic syndrome, probably mainly through decreasing oxidative stress and reducing PPARα expression, and the subsequent reduced expression in the liver of genes related to steatosis.     

Vitamin D3 regulation of body fat,cytokines, and calpain gene expression

BACKGROUND: We conducted an in vivo experiment to determine whether vitamin D₃ acts as a fat synthesizer and/or meat tenderizer in mice. At 6 weeks of age, 20 male C57BL/6 wild‐type mice were randomly divided into two groups (10 mice per group) and fed a modified AIN93G diet with (vitamin D₃ diet) or without (basal diet) 10 IU 25‐OH‐cholecalciferol kg^?3 for 3 weeks. RESULTS: When vitamin D₃ was fed to mice for 3 weeks, body fat was significantly increased compared to mice fed a basal diet. There was, however, no difference in body weight between the two groups. Vitamin D₃ increased the gene expressions of pro‐inflammatory cytokines and peroxisome proliferator‐activated receptor gamma, but decreased interleukin‐15 in adipose tissue through nuclear vitamin D receptor and uncoupling protein‐2 signals. The muscle inducible nitrate oxide synthase content of mice fed vitamin D₃ was higher than those fed a basal diet, while muscle arginase l showed a reverse phenomenon. longissimuss dorsi muscle of vitamin D₃‐fed mice showed more severe fat deposition than those fed a basal diet. Vitamin D₃ amplified muscle u‐ and m‐calpain protein content and suppressed muscle calpastatin protein content. CONCLUSION: These findings suggest that vitamin D₃ can be used as a fat synthesizer and meat tenderizer in meat‐producing animals. Copyright © 2011 Society of Chemical Industry     

白藜芦醇对高脂诱导肥胖小鼠生长性能及肝脏糖脂代谢、能量代谢的影响

研究添加白藜芦醇对高脂日粮诱导肥胖小鼠的体重、采食量、脂质代谢、糖代谢及能量代谢的影响。选取40只C57BL/6J雄性小鼠,随机分成4组,分别采用低脂日粮(LFD)、低脂日粮+0.0276%白藜芦醇(LR)、高脂日粮(HFD)、高脂日粮+0.04%白藜芦醇(HR)饲喂12周。结果表明:与饲喂低脂日粮小鼠相比,高脂日粮组小鼠的体重显著增加(p<0.05),前4周的采食量显著减少(p<0.05),血清中谷草转氨酶(AST)和谷丙转氨酶(ALT)活性显著升高(p<0.05),肝脏中ALT和AST活性显著下降(p<0.05),脂质过氧化物(LPO)和丙二醛(MDA)含量均显著升高(p<0.05),己糖激酶(HK)、丙酮酸激酶(PK)和琥珀酸脱氢酶(SDH)活力显著下降(p<0.05);另外,饲喂高脂日粮小鼠肝脏MDH1、Sdha、PGC-1α mRNA的表达量显著下降(p<0.05)。饲喂添加了白藜芦醇的高脂日粮后,与高脂日粮组比,小鼠的体重显著降低(p<0.05),采食量显著增加(p<0.05),血清中AST和ALT活性显著降低(p<0.05),肝脏中AST活性显著升高(p<0.05),LPO和MDA含量显著降低(p<0.05),HK和PK活力显著升高(p<0.05)。另外,饲喂白藜芦醇对高脂日粮导致的肝脏中Hk2、Pkm、Cs、MDH1、Sdha mRNA表达量降低有显著的提高作用(p<0.05)。综上所述,日粮中添加0.04%的白藜芦醇能一定程度地缓解高脂日粮造成小鼠机体损伤,修复机体的脂质代谢、糖代谢和能量代谢。     

Membrane-rich milk fat diet provides protection against gastrointestinal leakiness in mice treated with lipopolysaccharide

Milk fat globule membrane is a protein-lipid complex that may strengthen the gut barrier. The main objective of this study was to assess the ability of a membrane-rich milk fat diet to promote the integrity of the gut barrier and to decrease systemic inflammation in lipopolysaccharide (LPS)-challenged mice. Animals were randomly assigned to one of 2 American Institute of Nutrition (AIN)-76A formulations differing only in fat source: control diet (corn oil) and milk fat diet (anhydrous milk fat with 10% milk fat globule membrane). Each diet contained 12% calories from fat. Mice were fed diets for 5 wk, then injected with vehicle or LPS (10 mg/kg of BW) and gavaged with dextran-fluorescein to assess gut barrier integrity. Serum was assayed for fluorescence 24 h after gavage, and 16 serum cytokines were measured to assess the inflammatory response. Gut permeability was 1.8-fold higher in LPS-challenged mice fed the control diet compared with the milk fat diet. Furthermore, mice fed the milk fat diet and injected with LPS had lower serum levels of IL-6, IL-10, IL-17, monocyte chemotactic protein (MCP)-1, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and IL-3 compared with LPS-injected mice fed the control diet. The results indicate that the membrane-rich milk fat diet decreases the inflammatory response to a systemic LPS challenge compared with corn oil, and the effect coincides with decreased gut permeability.     

Protective Effect of Dietary Ghrelin‐Containing Salmon Stomach Extract on Mortality and Cardiotoxicity in Doxorubicin‐Induced Mouse Model of Heart Failure

Ghrelin exhibits a cardioprotective effect. We examined whether orally administered ghrelin‐containing salmon stomach extract (sSE) instead of chemically synthesized ghrelin protects against doxorubicin (DOX)‐induced cardiotoxicity in mice. Mice were divided into four groups: (i) the control, (ii) DOX groups were fed a control diet (AIN‐93G), (iii) the sSE, and (iv) DOX + sSE groups were fed a 10% sSE diet (AIN‐93G + 10% sSE). After a 4‐week pretreatment of sSE, DOX or saline was administered to the corresponding groups by intraperitoneal injection. The groups fed the 10% sSE diet consumed significantly more food than the groups fed the control diet before the DOX injection. No mortality was observed in the DOX + sSE group, whereas 40% (2 of 5) mortality was observed in the DOX group. Compared with the DOX group, levels of ascites and plasma cardiac troponin I improved in the DOX + sSE group. Significantly lesser DOX‐induced collagen accumulation was observed in the left heart ventricle of the DOX group than in that of the DOX + sSE group. These results suggest that the dietary ghrelin contained in sSE mimics synthetic ghrelin in cardioprotective effect. Ghrelin in sSE (45 pmol/g) and the food intake‐stimulating effect of sSE may explain, at least in part, the protective effect of orally administered teleost ghrelin.     

杜仲籽油对2型糖尿病KKAy小鼠糖脂代谢及肠道菌群的影响

目的 探讨杜仲籽油对2型糖尿病KKAy小鼠糖脂代谢及肠道菌群的影响.方法 24只KKAy小鼠随机分为3组(模型组、阳性药组、杜仲籽油组),8只C57BL/6J小鼠为正常组.实验7周后测定小鼠体重、空腹血糖和空腹胰岛素、糖耐受量、血脂四项和肝功能两项,进行肝脏油红O染色和小鼠肠道菌群检测.结果 与模型组相比,杜仲籽油组降...     

Effects of Tomato and Soy Germ on Lipid Bioaccumulation and Atherosclerosis in ApoE−/− Mice

Dietary patterns with cardiovascular benefits have been recommended, but the relative contributions of individual foods and food components, alone or in combination, remain undefined. Male ApoE^?/? mice were fed either a purified AIN‐93G control diet, a Western diet (WD), or a WD with 10% tomato powder (TP), 2% soy germ (SG), or the combination, for 4 wk (n = 10 per group). Plasma total cholesterol and triglycerides were measured with enzymatic colorimetric kits, and serum amyloid A (SAA) was measured by ELISA. Liver lipids were extracted with chloroform:methanol, and triglycerides, free and esterified cholesterol measured with enzymatic colorimetric kits. Expression of Cyp27a1, Cyp7a1, Abcg5, and Abcg8 in the liver was determined by quantitative polymerase chain reaction. Sections of the aortic root and aorta were cut and stained with hematoxylin and eosin (H&E) to assess extent of atherosclerotic lesions. WD‐fed animals had greater liver and adipose weights, plasma cholesterol and SAA, hepatic lipids, and atherosclerosis than AIN‐93G animals. TP and SG did not decrease atherosclerosis as measured by H&E‐stained sections of the aortic root, aortic arch, and descending aorta. The TP diets further increased plasma cholesterol, but also led to increased expression of the Abcg5/8 transporters involved in cholesterol efflux. Addition of SG alone to the WD attenuated WD‐induced increases in plasma cholesterol, liver lipids, and gonadal adipose weight. The results of this study do not support the use of either TP or SG for reduction of atherosclerosis, but suggest some beneficial effects of SG on lipid metabolism in this model of cardiovascular disease.     

Taioba (Xanthosoma sagittifolium) Leaves: Nutrient Composition and Physiological Effects on Healthy Rats

Several studies have shown that fruits and vegetables contribute to protect against degenerative pathologies such as cardiovascular diseases, diabetes, and cancer, mainly due to the presence of dietary fiber (DF) and polyphenols. Taioba (Xanthosoma sagittifolium) is an edible aroid widely grown in many parts of Africa, America, and Asia. The tubers portions of taioba are widely consumed; however, the leafy portions are generally discarded, despite their high nutritive value. In this study, we have partly characterized the DF of lyophiized taioba leaf (LTL), and assessed the possible protective effects on biochemical parameters and on bile acid (BA) production in colon and cecum, when fed to healthy rats for 4 wk. Forty‐five Wistar rats were assigned to either of 5 groups: group 1 received AIN 93G diet (CG: Control); group 2 received AIN 93G containing 2.5% of cellulose + 2.5% inulin (CEIN_5%); group 3 received AIN 93G containing 2.5% of cellulose + 2.5% taioba fiber (CETA_5%); group 4 received AIN 93G containing 5% cellulose + 2.5% taioba fiber (CETA_7.5%); group 5 received AIN 93G containing 5% cellulose + 2.5% of inulin (CEIN_7.5%). LTL showed high contents of total fiber, predominantly comprising insoluble DF with glucose as the major monomer. Rats receiving LTL had increased fecal mass and fat excretion, and improved BA profiles by diminishing the proportion of secondary acids, thus suggesting that consumption of taioba leaf may have the property of lowering the risk of colon cancer.     

Body composition and hormonal effects following exposure to mycotoxin deoxynivalenol in the high-fat diet-induced obese mouse

Scope: To characterize the effects of ingesting the common foodborne mycotoxin deoxynivalenol (DON) on body weight and composition in the high‐fat (HF) diet‐induced obese mice, a model of human obesity. Methods and results: Female B6C3F1 mice were initially fed HF diets containing 45% kcal (HF45) or 60% kcal (HF60) as fat for 94 days to induce obesity. Half of each group was either continued on unamended HF diets or fed HF diets containing 10 mg/kg DON (DON‐HF45 or DON‐HF60) for another 54 days. Additional control mice were fed a low‐fat (LF) diet containing 10% kcal as fat for the entire 148‐day period. DON induced rapid decreases in body weights and fat mass, which stabilized to those of the LF control within 11 days. These effects corresponded closely to a robust transient decrease in food consumption. While lean body mass did not decline in DON‐fed groups, further increases were suppressed. DON exposure reduced plasma insulin, leptin, insulin‐like growth factor 1, and insulin‐like growth factor acid labile subunit as well as increased hypothalamic mRNA level of the orexigenic agouti‐related protein. Conclusion: DON‐mediated effects on body weight, fat mass, food intake, and hormonal levels in obese mice were consistent with a state of chronic energy restriction.