Docosahexaenoic acid-rich fish oil prevented insulin resistance by modulating gut microbiome and promoting colonic peptide YY expression in diet-induced obesity mice

It is unclear how docosahexaenoic acid(DHA)improves insulin resistance via modulating gut microbiome in obese individuals.We used diet-induced obesity(DIO)mice as a model to study the effects of DHA-rich fish oil(DHA-FO)on host metabolic disorders and colonic microbiome.DHA-FO reduced fat deposition,regulated lipid profiles and alleviated insulin resistance in DIO mice.Probably because DHA-FO prevented the permeation of lipopolysaccharide across intestinal epithelial barrier,and promoted peptide YY(PYY)secretion via the mediation of short chain fatty acids receptor(FFAR2)in colon.Furthermore,DHA-FO might regulate PYY expression by reversing microbial dysbiosis,including increasing the abundance ofAkkermansia muciniphila and Lactobacillus,and suppressing the growth of Helicobacter.DHA-FO also altered gut microbial function(e.g."linoleic acid metabolism")associated with PYY expression(r>0.80,P<0.05).Herein,DHA-FO enhanced insulin action on glucose metabolism by altering gut microbiome and facilitating colonic PYY expression in DIO mice.

The Effects of Xylitol on Body Weight Loss Management and Lipid Profile on Diet-Induced Obesity Mice

Xylitol is an alternative sweetener which has been previously reported to have many beneficial effects such as prevention from dental caries, reduction of visceral fat and increased synthesis of collagen. However, its role in body weight loss management has not been uncovered before. This study sought to investigate the effects of xylitol on body weight loss management, blood glucose and lipid profile on diet-induced obesity (DOI) mice. Fifteen male mice were subjected to high fat diet (60 kcal%) and normal drinking water for 28 days and then randomly divided into three (control, glucose and xylitol) groups. Each group of mice was then fed with normal diet for another 28 days with supplied normal drinking water (control);glucose solution 10% and xylitol solution 10%. Body weight loss was found to be significantly high in xylitol mice (2.56 ± 0.21, p = 0.003) compared to the other two groups. Lowest blood glucose level was found in the control group mice with the mean 7.65 ± 0.10 (p = 0.001). Xylitol mice had also showed the lowest total cholesterol level (4.20 ± 0.90, p = 0.000) than the other groups, but highest in HDL level (2.72 ± 0.14, p = 0.000). In conclusion, these findings proved that xylitol has the potential to reduce body weight, lowering the blood glucose but yet increase the HDL level.

Bitter Melon Powder Protects against Obesity-associated Fatty Liver Disease by Improving Colonic Microenvironment in Rats with High-fat Diet-induced Obesity

This study explored how bitter melon powder （BMP） alters the colonic microenvironment during the development of obesity-associated fatty liver in rats. We observed that BMP effectively inhibited the body weight gain and lipid accumulation in the liver, ameliorated glucose intolerance, and increased the colon weight after an 8-week treatment compared to that in the high-fat diet （HFD） group. BMP significantly decreased fecal water toxicity towards HT-29 cells, as revealed by the cell counting kit （CCK）-8 assay results, and the mRNA expression of Toll-like receptor 4 （TLR4） in colon mucosa. Additionally, gut permeability in the BMP group was restored to normal levels. Finally, BMP alleviated the inflammatory state of the rat colon mucosa and liver tissues as well as the systemic inflammation.

Monascus pilosus-fermented black soybean inhibits lipid accumulation in adipocytes and in high-fat diet-induced obese mice

Objective:To explore the anti-obesity effects and the mechanism of action of Monascus pilosus(M.pilosus)-fermented black soybean(MFBS)extracts(MFBSE)and MFBS powders(MFBSP)in adipocytes and high-fat diet(HFD)-induced obese mice,respectively.Methods:Black soybean was fermented with M.pilosus,and the main constituents in MFBS were analyzed by HPLC analysis.In vitro,MFBSE were examined for anti-adipogenic effects using Oil-Red O staining.In vivo,mice were fed a normal-fat diet(NFD)control,HFD control or HFD containing 1 g/kg MFBSP for 12 weeks,and then body weight gain and tissues weight measured.Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects.Results:MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity.MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice.MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes,such as peroxisome proliferator-activated receptorγ(PPARγ),fatty acid-binding protein 4(FABP4),and fatty acid synthase(FAS),in adipocytes and in white adipose tissue(WAT)of HFD-induced obese mice.Conclusions:These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFDinduced obese mice.

Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy

AIM:To characterize development of diet-induced nonalcoholic steatohepatitis(NASH)by performing live biopsy in wild-type and genetically obese mice.METHODS:Male wild-type C57BL/6J(C57)mice(DIO NASH)and male Lep ob/Lep ob(ob/ob)mice(ob/ob-NASH were maintained on a diet high in trans-fat(40%)fructose(22%)and cholesterol(2%)for 26 and 12 wk respectively.A normal chow diet served as control in C57 mice(lean chow)and ob/ob mice(ob/ob chow)After the diet-induction period,mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted.Mice were then stratified into groups counterbalanced for steatosis score and fibrosi stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk.Global gene expression in liver tissue was assessed by RNA sequencing and bioin formatics.Metabolic parameters,plasma liver enzyme and lipids(total cholesterol,triglycerides)as well a hepatic lipids and collagen content were measured b biochemical analysis.Non-alcoholic fatty liver disease activity score(NAS)(steatosis/inflammation/ballooningdegeneration)and fibrosis were scored.Steatosis and fibrosis were also quantified using percent fractional area.RESULTS:Diet-induction for 26 and 12 wk in DIONASH and ob/ob-NASH mice,respectively,elicited progressive metabolic perturbations characterized by increased adiposity,total cholesterol and elevated plasma liver enzymes.The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis.Overall,the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice.During the eight week repeated vehicle dosing period,the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation.Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice(0 vs4.7±0.4,P<0.001 compared to lean chow)and ob/ob-NASH mice(2.4±0.3 vs 6.3±0.2,P<0.001compared to ob/ob chow),respectively.Furthermore,fibrosis stage was significantly elevated for DIO-NASH mice(0 vs 1.2±0.2,P<0.05 compared to lean chow)and ob/ob NASH(0.1±0.1 vs 3.0±0.2,P<0.001compared to ob/ob chow).Notably,fibrosis stage was significantly(P<0.001)increased in ob/ob-NASH mice,when compared to DIO-NASH mice.CONCLUSION:These data introduce the obese dietinduced DIO-NASH and ob/ob-NASH mouse models with biopsy-confirmed individual disease staging as a preclinical platform for evaluation of novel NASH therapeutics.

Effects of Maternal Linseed Oil Supplementation on Metabolic Parameters in Cafeteria Diet-induced Obese Rats

Because linseed oil may influence maternal and fetal metabolisms, we investigated its role in the modulation of lipid metabolism in cafeteria diet-induced obese rats and their offspring. Female Wistar rats were fed control or cafeteria food, which were either supplemented or not supplemented with linseed oil （5%） for I month before and during gestation. At parturition, serum and tissue lipids and enzyme activities were analyzed. Cafeteria diet induced adverse metabolic alterations in both mothers and offspring. Linseed oil improved metabolic status. In conclusion, linseed oil displayed health benefits by modulating tissue enzyme activities in both obese mothers and their newborns.

Comparative study on the difference of obesity model induced by two kinds of high fat diet in Sprague-Dawley rats

Objective: To explore the differences of obese Sprague-Dawley(SD)rats model induced by lard oil high-fat(HF)diet or purified HF diet. Methods: SD weanling rats were randomly divided into three groups: D1 group,where rats were fed by lard oil HF diet;D2 group,where rats were fed by purified HF diet;C group,where rats were fed on chow. After 12 weeks,diet-induced obesity rat(stop 33% based on weight)were selected for further study,and the rest rats from group D1 and D2 were excluded. The food intake and weight were weighted daily and weekly,respectively. The subcutaneous,visceral and total fat contents of rats was measured by 256-row CT scan and the Lee index was calculated accordingly. The kidney,liver,testis,spleen and heart were weighted respectively. Serum leptin and insulin levels were quantified. The pathology in liver and adipose tissues were analyzed by HE staining. Oral glucose tolerance test(OGTT)was used to compare the glucose tolerance ability. Serum total cholestero(lT-CHO),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),triglyceride(TG)and inflammatory cytokines IL-6,TNF-α were detected as well. Results: After 12 weeks,the body weight,subcutaneous fat,visceral fat,total fat mass,wet weight of liver,kidney and heart,area under blood glucose curve and the levels of serum insulin,leptin,T-CHO,LDL-C,TG,IL-6 and TNF-α in group D2 were significantly increased compared to those of group C and group D1. HDL-C of group D2 was markedly lower than that in group C(P<0. 05). The visceral fat,total fat content and HDL-C in group D1 were significantly different from those of group C(P<0. 05). Steatosis and enlarged adipocyte were found in the livers of rats in group D1 and D2,and the lesions were more significant in group D2. Conclusion: Purified HF diet was more effective in inducing metabolic abnormalities,steatosis,peripheral chronic inflammation in obese SD rat models. But lard oil HF diet was more economical when only inducing visceral steatosis was required.

基于下丘脑瘦素受体介导的JAK2/STAT3通路探讨穴位埋线治疗食源性肥胖大鼠的中枢机制

【目的】观察穴位埋线对食源性肥胖(DIO)大鼠体质量、脂代谢、血清瘦素和下丘脑瘦素受体(LepR)介导的Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)通路mRNA及蛋白表达的影响。【方法】将40只雄性SD大鼠随机分成正常组10只和造模组30只。采用高脂饮食诱导建立DIO大鼠模型。造模成功后将成模大鼠随机分为模型组、埋线组和埋线+AG490(JAK2/STAT3通路阻断剂)组,每组10只。埋线组、埋线+AG490组于造模成功后第1、8、15、22天进行埋线,穴位选取中脘、水道、天枢、脾俞、胃俞、三焦俞,共治疗4次,埋线+AG490组穴位埋线治疗期间每天腹腔注射AG4901 mg/kg;正常组和模型组仅抓取固定。治疗前后测量体质量。治疗后检测脂代谢指标甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)以及血清瘦素水平,实时定量聚合酶链反应(RT-PCR)法检测下丘脑LepR、JAK2、STAT3的mRNA表达,Western Blot法检测下丘脑LepR、JAK2、STAT3的蛋白表达。【结果】治疗前,与正常组比较,模型组、埋线组、埋线+AG490组体质量均升高(P<0.01),与模型组比较,埋线组、埋线+AG490组体质量无显著性差异(P>0.05)。治疗后,与正常组比较,模型组体质量,瘦素及TG、TC、LDL-C水平升高,LepR、JAK2、STAT3 mRNA及蛋白表达水平降低(均P<0.01);与模型组比较,埋线组体质量,瘦素及TG、TC、LDL-C水平降低,LepR、JAK2、STAT3 mRNA及蛋白水平升高(均P<0.01);与埋线+AG490组比较,埋线组体质量,瘦素及TG、TC、LDL-C水平降低,LepR、JAK2、STAT3 mRNA及蛋白水平升高(P<0.05或P<0.01)。【结论】穴位埋线对DIO大鼠具有良好的减重降脂作用,其中枢机制可能与下调血清瘦素水平,激活下丘脑LepR介导的JAK2/STAT3通路有关。

Changes of Neuronal Activities after Gut Electrical Stimulation with Different Parameters and Locations in Lateral Hypothalamus Area of Obese Rats

This study tested the effects of the gastrointestinal pulse train electrical stimulation with different parameters and at different locations on the neuronal activities of the lateral hypothalamus area（LHA） in obese rats in order to find the optimal stimulation parameter and location. Eight gastric electrical stimulations（GES） with different parameters were performed and the neuronal activities of gastric-distension responsive（GD-R） neurons in LHA were observed. The effects of stimulations with 8 parameters were compared to find the optimal parameter. Then the optimal parameter was used to perform electrical stimulation at duodenum and ileum, and the effects of the duodenal and ileac stimulation on the GD-R neurons in LHA were compared with the gastric stimulation of optimal parameter. The results showed that GES with the lowest energy parameter（0.3 ms, 3 mA, 20 Hz, 2 s on, 3 s off） activated the least neurons. The effects of GES with other parameters whose pulse width was 0.3 ms were not significantly different from those of the lowest energy parameter. Most gastric stimulations whose pulse width was 3 ms activated more LHA neurons than the smallest energy parameter stimulation, and the effects of those 3 ms gastric stimulations were similar. Accordingly, the lowest energy parameter was recognized as the optimal parameter. The effects of stimulations with the optimal parameter at stomach, duodenum and ileum on the LHA neuronal activities were not different. Collectively, gastrointestinal electrical stimulation（GIES） with relatively large pulse width might have stronger effects to the neuronal activities of GD-R neurons in LHA of obese rats. The effects of the GIES at different locations（stomach, duodenum and ileum） on those neurons are similar, and GES is preferential because of its easy clinical performance and safety.

Adipose tissue resistin gene expression in DIO and DR rats

Objective： To investigate the expression of resistin gene in diet-induced obesity （DIO） and diet resistance （DR） rats. Methods： DIO and DR models were prepared with male SD rats after 6 weeks feeding by a diet of relatively high fat, sucrose, and caloric content （HE diet）. Body-weight, fat mass, and the concentration of serum insulin were measured, and the expression of resistin and Peroxisome proliferator-activated receptory-7（PPAR-7） gene in whit adipose tissue （WAT） was also detected by RT-PCR. Results： ① Body weight, fat mass and the concentration of serum insulin were significantly increased in DIO rats and decreased in DR rats. ② The expression of resistin and PPAR7 gene was upregulated in DIO group and supressed in DR group, but the expression of resistin was not detectable in all samples within three groups. Conclusion： Resistin may serve as a link between obesity and insulin resistance, but the individual difference is enormous.

Reducing obesity and inflammation in mice with organically-derivatized polyoxovanadate clusters

Obesity,characterized by the dysregulation of energy balance in adipose tissue and other metabolic organs,is frequently accompanied by chronic low-grade inflammation.As long-acting insulin sensitizers,the organically-derivatized polyoxovanadates(POVs),can extend the dosing interval of antidiabetic drugs from hourly to almost daily.In this work,the protective activity of POVs is investigated by an eight-week in vivo experiment,in which a small amount of POVs was administrated orally to a mouse model of dietinduced obesity every day.The present study shows that administration of POVs significantly decreases the body weight of mice,reduces adipose tissue accumulation,and simultaneously reduces adipose tissue inflammation.In addition,the anti-obesogenic population of i NKT cells is protected potentially by POVs,which subsequently alleviates visceral adipose tissue inflammation in high-fat-diet(HFD)-fed mice against diet-induced obesity.By contrast,the change in body weight after POV treatment is the result of a substantial reduction in fat mass,with no obvious effects on lean body mass.These findings demonstrate that supplementary of POVs would be an effective way to combat obesity and metabolic disorders while lowering metabolic inflammation.

Calorie control increased vaspin levels of serum and periepididymal adipose tissue in diet-induced obese rats in association with serum free fatty acid and tumor necrosis factor alpha

Background Vaspin was recently identified as a novel adipokine that is predominantly secreted from adipose tissue and exerts insulin-sensitizing effects. This study was undertaken to elucidate the regulative effects of calorie control on the expression of vaspin and its potential mechanism.Methods Diet-induced obese Sprague Dawley （SD） rats were adopted as experimental models and accepted interventions of various ingestions and pioglitazone. Various differentiated stages of cultured 3T3-L1 cells were dealt with pioglitazone or TNFα in vitro for 48 hours to further verify findings in animal experiments.Results The rats were successfully induced into an obese experimental model with hyperinsulinemia, hyperlipidemia, and increased serum free fatty acid and TNFa by 12-week high-fat diet. It was found that depending on whether the rats were fed by a high-fat diet or a basal diet, there was extremely higher vaspin in the periepididymal fat pad than in subcutaneous adipose tissues by 16 weeks. Vaspin in sera and the periepididymal fat pad was much lower in rats with a high-fat diet than those with a basal diet （all P 〈0.05）, but vaspin in subcutaneous fat tissues was prone to increase in rats with a high-fat diet. A 4-week calorie restriction or pioglitazone on the obese rats resulted in a partial recovery of vaspin levels in sera and periepididymal adipose tissues, especially the latter revealed a more obvious superiority and increased vaspin levels of subcutaneous adipose. Surprisingly, the treatment of 4-week high-fat diet on non-obese rats did not significantly depress vaspin of sera and periepididymal adipose tissues. However, it is unknown if re-feeding generated the effect on vaspin levels of obese and non-obese rats on sera or adipose tissues. The correlation analysis showed that vaspin levels of serum and periepididymal fat tissues were negatively correlated with serum FFA, TNFα and insulin; meanwhile, there was a positive correlation between serum vaspin and vaspin of periepididymal fat tissues. Pioglitazone enhanced vaspin levels in cultured 3T3-L1 cells and supernatant in various differentiated stages, and this effect became more and more obvious along with the change of preadipocytes into mature fat cells. Administration of TNFα caused suppression on vaspin expression in differentiated stages of 3T3-L1 cells.Conclusions The present data indicated that a long-term high-fat diet could induce obesity metabolic syndrome in SD rats and finally lead to lower vaspin of sera and periepididymal fat, while pioglitazone and chronic calorie-control ingestion could enhance the production of vaspin. It was undoubtedly demonstrated that vaspin expression was strongly associated with insulin sensitivity, serum FFA, and TNFα.

TRPC5 is essential in endothelium-dependent contraction of aorta from diet-induced obese mice

The role of the Ca^(2+)-permeable ion channel TRPC5 in regulating vasocontraction in obesity is poorly understood.Here,we investigated whether TRPC5 contributes to vascular dysfunction in obesity by promoting endothelium-dependent contraction via activation of cytosolic phospholipase A2(cPLA_(2))in the aortic endothelial cells of obese mice.Acetylcholine-induced endothelium-dependent relaxation and contraction in the aorta were measured us-ing wire myography.PLA_(2)activity was measured by the fluorogenic PLA_(2)substrate Bis-BODIPY^(TM)FL C_(11)-PC.The intracellular Ca^(2+)level in response to acetylcholine was measured by Fluo-4 fluorescence.Endothelium-derived contracting factors were assessed by enzyme immunoassay.Diet-induced obesity(DIO)attenuated endothelium-dependent vasodilation,enhanced endothelium-dependent contraction(EDC),and increased the expression of TRPC5 in the mouse aorta.Activation of TRPC5 promoted EDC in the wild-type mouse aorta,whereas pharma-cological inhibition and genetic knockout of TRPC5 decreased EDC in the DIO mouse aorta.Moreover,cPLA_(2)phosphorylation and activity were higher in aortic endothelial cells from DIO mice,and this was attenuated by inhibition and knockout of TRPC5.Cyclooxygenase 2(COX-2)expression was increased in DIO mouse endothe-lium and was decreased by a TRPC5 inhibitor and knockout of TRPC5.Release of prostaglandins F_(2α(PGF_(2α)and E 2(PGE 2)was involved in TRPC5-regulated EDC in DIO mice.This study demonstrated that TRPC5 contributes to endothelial and vascular dysfunction and is involved in EDC through activation of cPLA_(2)and enhanced COX-2-PGF_(2α)/PGE_(2)levels in DIO mice.

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。

肥胖SD大鼠骨骼肌组织中SOCS-3mRNA的表达

目的:初步探讨肥胖SD大鼠骨骼肌组织中SOCS-3mRNA的含量与高leptin血症的关系。方法:用高脂饮食制备饮食诱导的肥胖(DIO)SD大鼠模型,应用放射免疫分析法检测血清leptin水平,应用RT-PCR半定量检测骨骼肌组织中SOCS-3mRNA的含量,并进行相关分析。结果:DIO大鼠存在高leptin血症,但其骨骼肌组织中SOCS-3mRNA的含量与对照大鼠没有差别,而且骨骼肌组织中SOCS-3mRNA的含量与大鼠的肥胖程度及血清leptin水平没有相关性。结论:DIO大鼠的leptin抵抗与骨骼肌组织中SOCS-3mRNA的含量无关。

不同剂量STZ与高脂饲料联合诱导糖尿病小鼠模型

探讨不同剂量链脲霉素(streptozotocin,STZ)联合高脂膳食建立2型糖尿病小鼠模型的效果。选择C57BL/6J小鼠,5周龄开始饲喂高脂饲料,持续10周,将膳食诱导的肥胖(dietinduced obesity,DIO)小鼠随机分为对照组及3个试验组[分别为试验组A(腹腔注射STZ 50mg/kg)、B(腹腔注射STZ 70mg/kg)、C(腹腔注射STZ 100mg/kg)],每组均为10只动物。试验组小鼠腹腔注射STZ后与对照组一起继续饲喂高脂2周。分别检测各组小鼠造模前后空腹血糖,胰岛素水平及成模后糖耐量。结果表明试验A、B、C 3组的成模率分别为70%、90%、100%,其血糖含量(分别为229.4±8.72、349.4±6.71、432.5±11.0 mg/dL)显著地高于对照组(168.7±4.18mg/dL);其血浆胰岛素含量(分别为1.83±0.288,0.659±0.058,0.438±0.023ng/mL)明显低于对照组(2.95±0.218ng/mL)。不同STZ剂量可诱导不同程度的糖尿病症状。

High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids

AIM： To investigate whether high-fat-feeding is associ- ated with increased intestinal permeability via altera- tions in bile acid metabolism.METHODS： Male C57BI/6J mice were fed on a high-fat （n = 26） or low-fat diet （n = 24） for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile ac- ids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor （FXR） and tumor necrosis factor

Effect of mango seed kernel extract on the adipogenesis in 3T3-L1 adipocytes and in rats fed a high fat diet

Mangoes (Mangifera indica L.) are one of the most important tropical foods. The seed is one of the main by-products of mango processing. Therefore, it is important to find an economically viable use for this waste (e.g., as a food additive or supplement with high nutraceutical value). We investigated the anti-obesity effects of mango seed kernel extract with hot water (MSKE-W) in 3T3-L1 adipocytes and in a high fat diet (HFD)-induced obesity rat model. MSKE-W caused a significant decrease in the activity of glycerol 2-phosphate dehydrogenase in 3T3-L1 adipocytes without eliciting cell cytotoxicity and inhibited cellular lipid accumulation through down-regulation of transcription factors such as PPARγ and C/EBPα. In the animal model, rats fed an HFD containing 1% MSKE-W gained less weight than rats fed an HFD alone. The visceral fat mass in rats fed an HFD containing 1% MSKE-W tended to be lower than that in rats fed an HFD alone. Furthermore, histological examination of rat livers from an HFD showed steatohepatitis. However, rats on an HFD containning 1% MSKE-W showed no histopathological changes in liver tissue. Our results indicate that MSKE-W influences anti-obesity effects, both in vitro and in vivo, and suggest that MSKE-W provides a novel preventive potential against obesity.

补脾与醒脾药物抗DIO大鼠肥胖疗效及对脂肪激素和炎症因子的影响

目的:观察补脾、醒脾药物对饮食诱导肥胖(DIO)大鼠肥胖疗效及对脂肪激素和炎症因子的影响。方法:Wister大鼠120只,制作DIO大鼠40只和肥胖抵抗(DIO-R)大鼠10只,DIO大鼠分为DIO模型组、西布曲明组、醒脾组、补脾气组4组,分别以0.9%氯化钠溶液、西布曲明、醒脾药物、补脾气药物灌胃,空白对照组与DIO-R组予0.9%氯化钠溶液。灌胃16周,测量肥胖程度及脂肪含量。取血测定胰岛素抵抗指数(IR)、血糖、甘油三酯、胆固醇,肿瘤坏死因子(TNF-α)、脂联素(adiponectin)。取脂肪匀浆测定TNF-α、脂联素等有关脂肪激素和炎症因子。结果:DIO模型组体质量、体质量指数、脂肪系数、IR明显升高(P<0.01);血糖、血脂有增高趋势;血清和脂肪中脂联素下降(P<0.05),血清和脂肪中TNF-α升高(P<0.05,P<0.01)。经药物干预后,西布曲明组体重指数下降(P<0.05),脂肪匀浆TNF-α明显降低(P<0.01)。醒脾组血清和脂肪匀浆中TNF-α减低(P<0.05,P<0.01),血清脂联素升高(P<0.05)。补脾气组治疗后体质量、体质量指数、血糖和IR明显降低(P<0.01),血清和脂肪匀浆中TNF-α减低(P<0.05,P<0.01)、脂联素明显升高(P<0.01)。结论:补脾药物能抑制高脂饲料诱导的肥胖和胰岛素抵抗,优于醒脾药物,其机制与促进脂肪脂联素分泌,降低TNF-α水平有关。"脾气亏虚"是肥胖的病机关键之一。

Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice

The prevalence of obesity-associated conditions raises new challenges in clinical medication.Although altered expression of drug-metabolizing enzymes(DMEs)has been shown in obesity,the impacts of obese levels(overweight,obesity,and severe obesity)on the expression of DMEs have not been elucidated.Especially,limited information is available on whether parental obese levels affect ontogenic expression of DMEs in children.Here,a high-fat diet(HFD)and three feeding durations were used to mimic different obese levels in C57BL/6 mice.The hepatic expression of five nuclear receptors(NRs)and nine DMEs was examined.In general,a trend of induced expression of NRs and DMEs(except for Cyp2c29 and 3a11)was observed in HFD groups compared to low-fat diet(LFD)groups.Differentialeffects of HFD on the hepatic expression of DMEs were found in adult mice at different obese levels.Family-based dietary style of an HFD altered the ontogenic expression of DMEs in the offspring older than 15 days.Furthermore,obese levels of parental mice affected the hepatic expression of DMEs in offspring.Overall,the results indicate that obese levels affected expression of the DMEs in adult individuals and that of their children.Drug dosage might need to be optimized based on the obese levels.