Efficacy of Antisense Oligodeoxynucleotide of Neuropeptide Y Y5 Receptor on Treating of Hyperleptinemia by Intraventricular Administration in Diet-induced Obese Rats

Objective: To study the efficacy of antisense oligonucleotide of neuropeptide Y (NPY) Y5 receptor on treating hyperleptinemia by intracerebral ventricular administration in diet-induced obese rats.Methods: The obese rats were prepared by feeding a high-nutritive diet for 7 weeks. The lateral ventricle of obese rats was cannulated. Either 10 μl of different neuropeptide Y Y5 receptor oligodeoxynucleotide, including antisense, sense and missense oligodeoxynucleotide (5 g/L) or 10 μl saline was administered into the ventricle through cannula three times per day in every rat. Two days later the rats were slaughtered .The weights of both retroperitoneal and epididymal adipose tissues were measured, and the serum insulin and leptin were detected by radioimmunoassay method and the murine leptin ELISA kit respectively. Results: ①The level of serum was significantly higher in experimental rats than that in normal rats. Similarly, the level of serum insulin and the weights of both retroperitoneal and epididymal adipose tissues were increased in experimental rats. ②After the diet-induced obese rats were intraventricularly administered with NPY Y5 receptor antisense oligodeoxynucleotide, the levels of serum leptin and insulin were significantly decreased and combined with the reduction of weight in retroperitoneal adipose tissue. There was, however, no significant difference in the weight of epidymal adipose tissue between pre-treated and post-treated duration. ③There was significant positive correlation among the level of serum leptin, the level of serum insulin and the weight of retroperritoneal adipose tissue in diet-induced obese rats. Conclusion: Intracerebral ventricular administration of antisense oligodeoxynucleotide of neuropeptide Y Y5 receptor may alleviate hyperleptinemia in diet-induced obese rats and decrease the weight of retroperitoneal adipose tissue and the level of serum insulin.

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.

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.

Anti-Obesity, Anti-Atherosclerotic and Anti-Oxidant Effects of Pu-Erh Tea on a High Fat Diet-Induced Obese Rat Model

Pu-erh tea, a traditional Chinese beverage, has been believed to have many benefits to human health and without side effects. In this study, we systematically analyzed the main active components of Pu-erh tea and investigated its anti-obesity, anti-atherosclerotic and anti-oxidant effects using an obese rat model. Obesity was induced by feeding a high-fat diet and subsequently the experimental obese mice were fed with high-fat diet supplemented with low (2.5%), medium (5%) or high (7.5%) doses of Pu-erh tea powder for 6 weeks respectively. As result, the body weight gain of the rats was decreased by medium and high doses of Pu-erh tea treatments. Furthermore, the levels of serum total cholesterol (TC), triglyceride (TG) and atherosclerosis index (AI) were significantly lowered by Pu-erh tea compared to the control group. Conversely, high density lipoproteincholesterol (HDL-C) level of the rats was significantly elevated by Pu-erh tea treatments. In addition, Pu-erh tea treatments increased the activities of anti-oxidative enzymes such as superoxide dismutase (SOD) and glutathione peroxides (GSH-Px), whereas reduced the level of lipid peroxidation product malondialdehyde (MDA) in obese rats. Collectively, our find-ings revealed that Pu-erh tea exerts comprehensive benefits in anti-obesity, anti-atherosclerotic and anti-oxidant effects, therefore can be used as a promising functional food in obesity management.

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.

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.

Study on Action of Acupuncture on Ventromedial Nucleus of Hypothalamus in Obese Rats

Effects of acupuncture on the spontaneous discharge of nerve cells and levels of monoamine neurotransmitters in ventromedial nucleus of hypothalamus (VMH) of the obese rats were investigated. Results indicated that the levels of tyrosine (Tyr) and dopamine (DA) were lowered, the levels of 5-hydroxytryptamine (5-HT) and 5-hydoxyindole acetic acid (5-HIAA) increased, and the frequency of the spontaneous discharge of nerve cells in VMH lowered in the obese rat group as compared with the normal group. When acupuncture obtained the effect of weight reduction, the frequency of spontaneous discharges of nerve cells in VMH were markedly increased, and the levels of Tyr, DA and tryptamine (Typ) and 5-HT/5-HIAA ratio elevated, and the 5-HT level lowered. It is suggested that the virtuous regulative action of acupuncture on VMH might be one of the key factors in acupuncture for weight reduction.

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.

Effect of Soy Isoflavone Crude Extract Supplementation on High Fat Diet-induced Insulin Resistance in Ovariectomized Rats

Female Wister rats aged 8 weeks were randomly divided into sham operation group, ovariectomized （OVX） control group, and 20VX groups fed with soy isoflavone crude extract supplementation. The rats had free access to high fat diet and water for 9 weeks. No significant difference was found in body weight （BW）, total abdominal fat, food intake and food utilization rate between OVX control group and 20VX groups. However, the fasting blood glucose and blood lipid levels were significantly higher in 20VX groups than in OVX control group （P〈0.05）. Intraperitoneal glucose tolerance test （IGTI＂） showed that the area under AUC was smaller in 20VX groups than in OVX control group （P〈0.05）. These findings showed that soy isoflavone crude extract supplementation can improve glucose tolerance and prevent high fat diet-induced insulin resistance in ovariectomized rats.

Effects of Acupuncture on Monoamine Neurotransmitters in Raphe Nuclei in Obese Rats

Effects of acupuncture on the levels of neurotransmitters in the raphe nuclei were investigated in obeserats.It was found that the levels of tryptophan (Trp) and 5-hydroxyindoleacetic acid (5-HIAA) wereincreased,and 5-hydroxytryptamine (5-HT) level and 5-HT/5-HIAA ratio decreased in the raphe nucleiof the obese group as compared with the normal group;and that acupuncture could produce weightreduction,increase the 5-HT level and 5-HT/5-HIAA ratio,and decrease the contents of Trp and5-HIAA,but did not change the levels of dopamine (DA) and noradrenaline (NA).It is indicated thatbenign regulative action of acupuncture on 5-HT and its metabolism in the raphe nuclei is possibly oneof the factors for reducing weight by acupuncture.

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.

Partial Physiologic Differences between High-fat Diet Induced Obesity-prone and Obesity-resistant Rats

Objective: To observe the differences of partial physiologic indexes including weight, food intake, Lee's index, the wet weight of fat pad, plasma lipids and the genetic expression of LPL mRNA in adipose tissue between obesity-prone rats (OP) and obesity-resistant rats (OR) on a high-fat diet. Methods: After 1 week of free access to a high-fat diet (HFD), 48 rats were separated on the basis of 1 week body weight percentage gained in OP (OP≥P75) or OR (OR≤P25) groups. Rats were continuously fed on the HFD for another 4 weeks. The body weight and food intake were recorded in the course of model-making. And the Lee's index, the plasma lipid and lipoproteins, the wet weight of both epididymal and retroperitoneal fat pad were measured after the rat was killed. And the level of LPL mRNA expression in adipose tissue was detected by Northern Blot technique. Results: ① In OP rats, the speed of body weight gain, the cumulative energy intake, the Lee's index, and the wet weight of fat pad at both epididymal and retroperitoneal sites were significantly higher than those in OR rats, but there was no significant difference in the level of plasma lipid and lipoproteins between these two groups. ② After 1 week and 5 weeks on the high-fat diet, the gain of body weight in OP rats were about 6.45 and 4.25 times of those in OR rats. Meanwhile, the cumulative energy intake in OP rats was only about 1.13 and 1.15 times of those in OR rats. ③ Despite the depressive effect of the high-fat diet on the level of LPL mRNA expression in adipose tissue, there was a significant level of LPL mRNA in adipose tissue of OP rats compared with that in OR rats. Conclusion: The physiologic differences exist between OP and OR rats. Besides a higher level of energy intake, the higher energy efficiency associated with LPL mRNA expression in adipose tissue may also contribute to the enhancement of susceptibility to obesity in OP rats.

Effects of octreotide on glucose transporter type 2expression in obese rat small intestine

AIM： TO investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 （GLUT2） in obese rat intestinal mucosa. METHODS： We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls. The obese rats were separated into an octreotide treated group 9f 16 rats and an obese group of 15. The intervention （：jroup was injected with octreotide at 40 ±g/kg body weight every 12 h for 8 d. Rat body weight was measured weekly to calculate Lee＇s index. After euthanization, maltase and sucrase activities in the small intestine were measured by activity assays, and the fasting plasma glucose level was measured. The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction and Western blotting assays. RESULTS： Body weight, Lee＇s index, fasting plasma glucose level, maltase activity in small intestinal mucosa, mucosa and apical GLUT2, GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group （605.61 ± 141.00 vs 378.54 ±111.75, 337.61 ± 10.82 vs 318.73 ± 20.10, 8.60± 1.38 vs 7.33 ± 0.70, 156.01 ± 58.81 vs 50.43 ± 30.49, 390 744.2± 62 469.21 vs 170 546.50 ± 50 646.14, 26 740.18 ±3809.60 vs 354.98± 57.19, 0.26± 0.11 vs 0.07± 0.02, and 2.08 ± 0.59 vs 1.27 ± 0.38, respectively, all P 〈 0.01）. Sucrase activity did not differ between the two groups. Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats （508.27 ± 94.39 vs 605.61 ± 141.00, 7.58 ± 1.51 vs 8.60±1.38, respectively, all P 〈 0.05）. The intestinal mucosa and apical GLUT2, expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group （269 975.2 ± 53 730.94 vs 390 744.2 ± 62 469.21, 3758.06 ± 364.51 vs 26 740.18 ± 3809.60, 0.08 ± 0.02 vs 0.26 ±0.11, and 1.31 ± 0.27 vs 2.08 ±0.59, respectively, all P 〈 0.01）. CONCLUSION： High fat dietinduced obesity is associated with elevated intestinal maltase activity, GLUT2 expression, and permanent apical GLUT2 in the small intestinal mucosa of rats. Octreotide can inhibit these effects.

Polygonatum sibiricum polysaccharides protect against obesity and non-alcoholic fatty liver disease in rats fed a high-fat diet

Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immunity. Previous studies have shown that insulin resistance(IR), oxidative stress, and inflammation are important factors in the induction of lipid metabolic diseases such as obesity. Therefore, in this study, we established a high-fat diet-induced rat model of obesity and nonalcoholic fatty liver disease(NAFLD) to explore the potential protective effect of P. sibiricum polysaccharides(PSPs) and the mechanisms behind it. After 4 weeks of high-fat diet feeding to induce obesity, the rats were treated with different doses of PSP solution or distilled water for 6 weeks. Compared with untreated obese rats, PSP-treated obese rats showed a decrease in body weight, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, hepatic aspartate aminotransferase and alanine aminotransferase activity, hepatic malondialdehyde content, and hepatic levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, as well as increased serum high-density lipoprotein cholesterol levels and hepatic superoxide dismutase, catalase, and glutathione peroxidase activity. Pathological analysis and immunoblotting of the liver tissues indicated that mechanistically, PSPs reduced obesity and NAFLD in rats by upregulating insulin receptor expression, increasing adenosine monophosphate-activated protein kinase phosphorylation, and downregulating sterol regulatory element-binding protein 2 and low-density lipoprotein receptor expression, thus promoting lipid metabolism, decreasing body weight, and reducing inflammation and oxidative stress caused by lipid accumulation. Based on these results, PSPs may have the potential to reduce obesity and NAFLD associated with a high-fat diet.

Impact of age on host responses to diet-induced obesity:Development of joint damage and metabolic set points

Background:Osteoarthritis is one of the leading causes of pain and disability worldwide,and a large percentage of patients with osteoarthritis are individuals who are also obese.In recent years,a series of animal models have demonstrated that obesity-inducing diets can result in synovial joint damage(both with and without the superimposition of trauma),which may be related to changes in percentage of body fat and a series of low-level systemic inflammatory mediators.Of note,there is a disparity between whether the dietary challenges commence at weaning,representing a weanling onset,or at skeletal maturity,representing an adult onset of obesity.We wished to evaluate the effect ofthe dietary exposure time and the age at which animals are exposed to a high-fat and high-sucrose(HFS) diet to determine whether these factors may result in disparate outcomes,as there is evidence suggesting that these factors result in differential metabolic disturbances.Based on dietary exposure time,we hypothesized that rats fed an HFS diet for 14 weeks from weaning(HFS Weanling) would demonstrate an increase in knee joint damage scores,whereas rats exposed to the HFS diet for 4 weeks,starting at 12 weeks of age(HFS Adult) and rats exposed to a standard chow diet(Chow)would not display an increase in knee joint damage scores.Methods:Male Sprague-Dawley rats were fed either an HFS diet for 14 weeks from weaning(HFS Weanling) or an HFS diet for 4 weeks,starting at 12 weeks of age(HFS Adult).At sacrifice,joints were scored using the modified Mankin Criteria,and serum was analyzed for a defined subset of inflammatory markers(Interleukin-6,leptin,monocyte chemoattractant protein-1,and tumor necrosis factorα).Results:When the HFS Weanling and HFS Adult groups were compared,both groups had a similar percent of body fat,although the HFS Weanling group had a significantly greater body mass than the HFS Adult group.The HFS Weanling and HFS Adult animals had a significant increase in body mass and percentage of body fat when compared to the Chow group.Although knee joint damage scores were low in all 3 groups,we found,contrary to our hypothesis,that the HFS Adult group had statistically significant greater knee joint damage scores than the Chow and HFS Weanling groups.Furthermore,we observed that the HFS Weanling group did not have significant differences in knee joint damage scores relative to the Chow group.Conclusion:These findings indicate that the HFS Weanling animals were better able to cope with the dietary challenge of an HFS diet than the HFS Adult group.Interestingly,when assessing various serum proinflammatory markers,no significant differences were detected between the HTS Adult and HFS Weanling groups.Although details regarding the mechanisms underlying an increase in knee joint damage scores in the HFS Adult group remain to be elucidated,these findings indicate that dietary exposure time maybe less important than the age at which an HFS diet is introduced.Moreover,increases in serum proinflammatory mediators do not appear to be directly linked to knee joint damage scores in the HFS Weanling group animals but may be partially responsible for the observed knee joint damage in the adults over the very short time of exposure to the HFS diet.

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.

Effects of a flavonoid-enriched orange peel extract against type 2 diabetes in the obese ZDF rat model

Effects of an enriched orange peel extract(OPE)against type 2 diabetes(T2D)were analyzed in ZDF rats which were hyperglycemic,dyslipidemic and express pro-inflammatory markers.Glucose related parameters were lowered in the lean control and metformin group as compared to ZDF vehicle controls.OPE was well tolerated and induced a decline in fasted blood glucose and increase levels of fed glucose although to a lesser degree as compared to metformin.However,OPE did not improve glucose tolerance but showed significantly elevated glucose levels.Furthermore,OPE treatment caused an increase of free fatty acids in a dose-responsive manner as well as elevated levels of cholesterol and LDL.The analysis of inflammatory mediators revealed a significant down-regulation of COX-2,ICAM-1,and TNF-˛in epididymal adipose tissue in response to OPE to a higher degree as compared to ibuprofen.In whole blood,IL-4 was upregulated in a dose-responsive manner as measured by ELISA.In summary,lipophilic OPE showed strong anti-inflammatory effects in adipose tissue,ambivalent effects against hyperglycemia,whereas hyperlipidemia was increased.Our study emphasize the complexity of anti-diabetic regimen suggesting a treatment with OPE to reduce inflammation in adipose tissue in combination with antidiabetic therapeutics as promising strategy against T2D.

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.

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.

B Vitamins Can Reduce Body Weight Gain by Increasing Metabolism-related Enzyme Activities in Rats Fed on a High-Fat Diet

B vitamins are enzyme cofactors that play an important role in energy metabolism.The aim of this study was to elucidate whether B vitamin administration can reduce body weight(BW)gain by improving energy metabolism-related enzyme activities in rats fed on a highfat diet.Fifty rats were randomly assigned to one of the following five groups:control group(C),including rats fed on standard rat chow;four treatment groups(H0,H1,H2,and H3),in which rats were fed on a high-fat diet.Rats in the H1 group were treated daily with 100 mg/kg BW thiamine(VB1),100 mg/kg BW riboflavin(VB2),and 250 mg/kg BW niacin(VPP);rats in the H2 group were treated daily with 100 mg/kg BW pyridoxine(VB6),100 mg/kg BW cobalamin(VB12),and 5 mg/kg BW folate(FA);and rats in the H3 group were treated daily with all of the B vitamins administered to the H1 and H2 groups.After 12 weeks,the BW gains from the initial value were 154.5±58.4 g and 159.1±53.0 g in the H1 and C groups,respectively,which were significantly less than the changes in the H0 group(285.2±14.8 g,P〈0.05).In the H0 group,the plasma total cholesterol(CHO)and triglyceride(TG)levels were 1.59±0.30 mmol/L and 1.55±0.40 mmol/L,respectively,which were significantly greater than those in the H1 group(1.19±0.18 mmol/L and 0.76±0.34 mmol/L,respectively,P〈0.05).The activities of transketolase(TK),glutathione reductase,and Na^+/K^+adenosine triphosphatase were significantly increased in the B vitamin-treated groups and were significantly greater than those in the H0 group(P〈0.05).Furthermore,the glucose-6-phosphate dehydrogenase,pyruvic acid kinase,and succinate dehydrogenase activities also were increased after treatment with B vitamins.Supplementation with B vitamins could effectively reduce BW gain and plasma levels of lipids by improving energy metabolism-related enzyme activities in rats,thus possibly providing potential benefits to humans.