Neuroinflammation attenuation effects by celastrol and PDIA3 in the amygdala, hippocampus and dorsal raphe nucleus of obese mice

Nowadays,roughly 603.7 million people are bothered by obesity[1].More seriously,obesity brings inflammation to the peripheral and central nervous system,which compromises the comorbidity of obesity,major depression[2],and cognitive deficits[3].Drug competent in the comorbidity is still lacking.In 2015,Liu et al.[4]reported celastrol(CEL)as a powerful anti-obesity agent.In our previous study.

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.

Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice

Objective:To evaluate possible lipid catabolism and body fat regulation effects of 3-caffeoylquinic acid in Green coffee bean extract(GCBE) in high-fat diet(HFD)-induced obese mice.Methods:Obesity was induced in mice using a HFD for four weeks.Then,mice were fed only HFD or HFD with GCBE at 50,100,and 200 mg/kg.Fatty acid synthesis mechanism regulation of body fat was investigated through real-time PCR and Western blot assay.Body fat reduction was measured through dual-energy X-ray absorptiometry.Results:In HFD-induced obese mice,GCBE treatment significantly decreased body weight gain,liver weight and white adipose tissue weights with regulation of adipose tissue lipolysis hormones,like adiponectin and leptin.GCBE treatment decreased mR NA expression levels of adipogenesis and adipocyte metabolism related genes in adipose tissues and the liver,and decreased the corresponding protein expression.Dual energy X-ray absorptiometry measurements were used to compare body fat between mice on high-fat and those treated with GCBE.GCBE treated mice had a lower fat mass compared to HFD alone fed mice and relative body weight and fat mass were markedly decreased.Conclusions:GCBE has a potential anti-obesity effect with lowering body fat accumulation by regulating adipogenesis and lipid metabolism-related genes and proteins in WAT and liver.

Amelioration of type 1 diabetes following treatment of non-obese diabetic mice with INGAP and lisofylline

Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies.

Comparative study on the weight loss and lipid metabolism by tea polyphenols in diet induced obese C57BL/6J pseudo germ free and conventionalized mice

The role of gut microbiota in terms of host health is becoming increasingly important.In this study,the comparative effects of tea polyphenols(TPs)on weight loss and lipid metabolism on conventionalized mice(CVZ)and pseudo germ-free(PGF)mice(treated with antibiotics)were investigated.Our findings revealed that high fat(HF)diet considerably increased the body weight,total fat and upsurge lipid indices in CVZ mice but PGF mice were not sensitive to the effect of HF diet as CVZ mice.After the dietary administration of TP,body weight,perirenal fat and epididymal fat,liver weight,glucose(GLU)level,total chloestrol(TC level),high density lipoprotein-cholesterol(HDL-C)level significantly lowered in PGF mice as compared to CVZ mice group.However,the area of fat cells and triglyceride(TG)level were significantly increased in PGF mice.In CVZ mice,TP intervention resulted in a considerable drop in the Firmicutes/Bacteroides ratio as compared to PGF mice.The intestinal flora of PGF mice was severely reduced after antibiotic treatment,while TP administration restored intestinal diversity;the abundance of Akkermansia and Lactobacillus increased,whereas the abundance of Enterobacteriaceae and Prevotella reduced.Overall,we can assume that PGF obese mice administered with TP have less anti-obesity effects compared to obese CVZ mice.

<i>In Vivo</i>Antioxidant Activity of Fucoxanthin on Obese/Diabetes KK-<i>A^y</i>Mice

Dietary intake of 0.1% fucoxanthin significantly reduced lipid hydroperoxide levels of liver and abdominal white adipose tissue (WAT) of obese/diabetes KK-Ay mice. The fucoxanthin supplementation also significantly reduced blood glucose level and hepatic lipid contents of the mice. Oxidative stress is known to be induced in hyperglycemia and high fat conditions. Therefore, in vivo antioxidant activity of fucoxanthin found in the present study could be attributed to its anti-diabetic effect and its decreasing effect on hepatic lipids. On the other hand, little effect of fucoxanthin on lipid hydroperoxide levels was found in normal ICR mice. Although the content of fucoxanthin metabolites in the abdominal WAT of KK-Ay mice was about 50 times higher that in the liver, there was little difference in its In Vivo antioxidant activity between in the liver and in the abdominal WAT. These results suggest that well-known ability of fucoxanthin to scavenge active oxygen species and/or free radicals would not be a main reason to explain its In Vivo antioxidant activity.

Effects of Siraitia grosvenorii extracts on high fat diet-induced obese mice:a comparison with artificial sweetener aspartame

Long-term artificial sweetener intake is linked to increased risk of obesity. In the present study, supplement of natural sweetener from Siraitia grosvenorii(SG)(or Momordica grosvenorii) fruit, compared with the artificial sweetener aspartame(ASM), was evaluated for anti-obesity effects on mice fed with high fat diet(HFD). We found that, in contrary to ASM, SG extracts prevented body weight gain, the insulin resistance and fat mass accumulation in HFD mice. SG extracts treatment inhibited the infiltration of inflammatory macrophages and lowered the levels of the fat inflammatory cytokines(leptin, macrophage chemoattractant protein 1(MCP-1) and tumor necrosis factor-α(TNF-α)) in adipose tissues. In addition, SG extracts supplement counteracted the remodeling of gut microbiota resulted from HFD. However, ASM supplement aggravated the HFD-induced obese performances, fat inflammation and dysregulation of gut microbiota. Taken together, our results indicate that supplement of SG extracts may represent a promising alternation of artificial sweeteners in preventing metabolic diseases.

Dietary Effect of Squalene on Lipid Metabolism of Obese/Diabetes KK-<i>A^y</i>Mice and Wild-Type C57BL/6J Mice

The purpose of this study was to evaluate the influence of squalene (SQ) on plasma and hepatic lipid levels of obese/diabetic KK-Ay mice and wild-type C57BL/6J mice. SQ supplementation significantly increased the HDL cholesterol of KK-Ay mice, which was paralleled with no significant difference in the total and non-HDL cholesterol levels. The increase in HDL cholesterol was also found in the plasma of normal C57BL/6J mice, but the difference was not significant. SQ administration significantly increased neutral lipids (NL) in the liver of KK-Ay mice, while no significant difference was observed in the polar lipids and the total cholesterol levels. The increase in NL was primarily due to the increase in TAG. However, the cholesterol level significantly increased due to SQ intake in the liver of C57BL/6J mice, while no significant difference was found in other lipid levels. The present study suggests that SQ may effectively increase HDL cholesterol level, an important anti-atherosclerotic factor, especially in subjects with metabolic disorders.

The Effect of High Carbohydrate Consumption on Glucose Levels and Antibody Production in Nonobese Diabetic Mice

The aim of this study was to evaluate the effect of chronic treatment with diets rich in carbohydrates on the IgM and IgG antibody production and the seric glucose concentration in diabetes. Nonobese diabetic (NOD) mice received, ad libitum, by oral route, the diet consisting of an aqueous extract (20 mg/mL) of the following flours: babassu mesocarp, manioc, corn or rice, during 120 days. The diet intake was monitored throughout this period. At the end, the weight variation, blood glucose, serum IgG and IgM antibody and IgM anti-insulin titers, were determined. The babassu and manioc flour extracts altered Purina chow intake and these animals also presented a significant increase in body weight. In contrast, treatment with rice flour resulted in a significant weight loss. Moderate to severe hyperglycemia was observed in the groups receiving rice and manioc, whereas treatment with babassu mesocarp flour and cornmeal resulted in hypoglycemia. The extracts did not alter the IgG concentration. On the other hand, the cornmeal extract caused a marked reduction in both total IgM and anti-insulin IgM antibody production. Although babassu mesocarp flour, cornmeal and manioc flour caused important variations in the parameters studied, only treatment with the rice flour extract anticipated the onset of diabetes in male mice genetically predisposed to the disease.

Pandanus amaryllifolius leaf extract increases insulin sensitivity in high-fat diet-induced obese mice

Objective: To examine the effect of Pandanus amaryllifolius(P. amaryllifolius) leaf extract on the insulin resistance state in obese ICR mice.Methods: Obesity was induced in mice fed with high-fat diet(45% fat) for 12 weeks. After the first six weeks on the diet, the obese mice were administered with the water extract of P. amaryllifolius leaf at 125 and 250 mg/kg/day, respectively for another six weeks. At the5 th week of treatment, oral glucose tolerance test was conducted. After six weeks of treatment, the levels of blood glucose, serum insulin, leptin, adiponectin, and lipid profiles were determined. The liver, muscle and epididymal fat tissues were removed for measuring the biochemical parameters and protein expression, as well as histological examination.Results: Six weeks of treatment with P. amaryllifolius led to a significant reduction in the blood glucose level as well as improvement in the insulin resistance. P. amaryllifolius also increased the liver glycogen storage and serum adiponectin and decreased the serum leptin levels. A reduction in the serum and hepatic triglyceride, and non-esterified fatty acid levels was also observed. The histological examination showed that the obese mice treated with P. amaryllifolius reduced the lipid droplet in liver tissue and adipocyte size in epididymal fat tissue. The treatment also increased the protein expression of glucose transporter 4 in the muscle and fat tissues.Conclusions: The treatment with P. amaryllifolius could decrease several parameters of impaired glucose and lipid metabolism. To the best of our knowledge, this is the first report on the role of P. amaryllifolius leaf extract in alleviating the insulin dysfunction in obesity state.

Effects of novel vaccines on weight loss in diet-induced-obese(DIO) mice

The purpose of the study was to test the therapeutic effects of novel vaccines for reducing weight gain and increasing weight loss in diet induced obesity （DIO） model. Male C57BL/6 J mice, fed a 60% Kcal fat diet for 8 weeks prior to the start of the study, were vaccinated via the intraperitoneal route with two formulations （JH17 ＆ JH]8） of chimeric-somatostatin vaccines at 1 and 22 days of the study. Control mice were injected with PBS. All mice continued to be feed the 60% Kcal fat diet for the week and food intake was measured weekly. At week 6 6 week study. Body weights were measured two times a mice were euthanized and a terminal bleed was made and antibody levels to somatostatin and levels of insulin-like growth factor 1 （IGF-1） were determined. Vaccination with both vaccine formulations induced a statistically significant body weight change over the study period, as compared with PBS controls. Percentage of baseline body weight was also significantly affected by vaccination during the study period. Vaccinates finished the study at 104% and 107% of baseline weight, JHI7 ＆ JH18 respectively, while untreated controls reached 115% of baseline weight. Food intake per mouse was similar in all mouse groups during the entire study. Control mice did not demonstrate any antibody titers to somatostatin, while all vaccinated mice had measurable antibody responses （〉 1：500,000 titer）. IGF-1 levels were not statistically significant among the groups, but were elevated in the JH18 vaccinates （mean 440.4 ng/mL） when compared with PBS controls （mean 365.6 ng/mL）. Vaccination with either JH17 or JH18 chimeric -somatostatin vaccines produced a statistically significant weight loss as compared with PBS controls （P 〈 0.0001）, even though the DIO mice with continually fed a 60% Kcal fat diet. The weight loss/lower weight gain observations were even more significant, as all mice consumed similar amounts of food for the entire study. The presence of high levels of anti-somatostatin antibodies at 6 weeks was correlative with the weight observations and confirmed the success of vaccination.

Rhinacanthus nasutus leaf improves metabolic abnormalities in high-fat diet-induced obese mice

Objective:To investigate the effect of Rhinacanthus nasutus(R.nasutus) leaf extract on impaired glucose and lipid metabolism in obese ICR mice.Methods:Obesity was induced in the male ICR mice by feeding them a high-fat diet(60 kcal%fat) for 12 weeks.After the first six weeks of the diet,the obese mice were administered with the water extract of R.nasutus leaves at 250 and 500 mg/kg per day for the next six weeks.Subsequently,the blood glucose,lipid profiles,insulin,leptin,and adiponectin levels were measured.The liver and adipose tissues were excised for histopathological examination and protein expression study.Results:After six weeks of the treatment,R.nasutus extract(at 250 and 500 mg/kg per day) was found to reduce the elevated blood glucose level,improve the insulin sensitivity,decrease the serum leptin,and increase the serum adiponectin levels.The obese mice treated with R.nasutus were found to have a reduction in the increased lipid concentrations in their serum and liver tissues.Moreover,treatment with R.nasutus reduced the fat accumulation in the liver and the large adipocyte size in the fat tissues.Interestingly,the administration with R.nasutus extract was marked by an increase in the hepatic peroxisome proliferators-activated receptor alpha,fat cell adiponectin,and glucose transporter 4 proteins.Conclusions:To the best of our knowledge,the present study is the first report on the impact of R.nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.

Anti-lipogenic effect of Senna alata leaf extract in high-fat diet-induced obese mice

Objective: To examine the effect of Senna alata(S. alata) leaf extracts on the regulation of lipid metabolism in high-fat diet-induced obese mice.Methods: The obesity condition was induced in the male ICR mice by feeding them with high-fat diet(45 kcal% fat) for 12 weeks. At the 7th week of diet feeding, the obese mice were treated with the water extract of S. alata leaf at 250 and 500 mg/kg/day, respectively, that continued for six weeks. At the end of the treatment period, the biochemical parameters were determined. The hepatic histology and the gene and protein expressions were also examined.Results: In comparison with the obese control mice, the mice treated with S. alata showed a significant reduction in the elevated blood glucose levels and a decrease in the serum insulin and leptin levels. A reduction in the serum total cholesterol, triglyceride,non-esterified fatty acid, and hepatic triglyceride levels were also observed. The histological examination of the obese mice treated with S. alata showed a reduced lipid accumulation in the liver tissue. Hepatic lipogenic gene expression showed that S. alata decreased the activity of sterol regulatory element binding protein 1c, fatty acid synthase,and acetyl-Co A carboxylase. S. alata could suppress hepatic peroxisome proliferatoractivated receptor gamma(PPARg) protein. Moreover, the protein expression of PPARa in liver tissue was clearly increased by S. alata treatment.Conclusion: The treatment with S. alata could decrease several parameters of impaired lipid metabolism in the obese mice by downregulating sterol regulatory element binding protein 1c and PPARg and upregulating PPARa. This study is the first report on the role of S. alata leaf extract in alleviating the abnormal lipid metabolism in obese conditions.

Enriched endoplasmic reticulum-mitochondria interactions result in mitochondrial dysfunction and apoptosis in oocytes from obese mice

Background： Maternal obesity alters oocytes and subsequent fetal metabolism. An increasing number of studies have shown that the endoplasmic reticulums（ER） or mitochondria have important effects on oocyte quality, but there has been no study of the effect of mitochondria-associated ER membranes（MAMs） on oocyte quality. The present study was designed to assess whether the level of MAM and MAM-related proteins were different in oocytes from obese and control mice.Results： First, oocytes from mice with high-fat-diet（HFD）-induced obesity had higher levels（either greater numbers or a higher proportion for the same numbers） of MAM than oocytes from control mice. The abundance of MAM-related proteins in oocytes from obese mice was significantly greater at both the messenger RNA and protein levels, including inositol 1,4,5-trisphosphate receptor, type 1（IP3R1）, inositol 1,4,5-trisphosphate receptor,type 2（IP3 R2） and phosphofurin acidic cluster sorting protein 2（PACS-2）. Further, there was an increase in mitochondrial Ca^（2＋）（[Ca^（2＋）]_m） which was associated with increased apoptosis and compromised cytoplasmic maturation in oocytes from obese mice. Down-regulation of MAM-related protein IP3R1 in oocytes from obese mice decreased [Ca^2＋]_mand apoptosis and improved cytoplasmic maturation but did not reduce the overal MAM level. However, down-regulating MAM-related protein PACS-2 in oocytes from obese mice did reduce the level of MAM and [Ca^（2＋）]_m, which decreased the rate of apoptosis and improved cytoplasmic maturation of oocytes from obese mice.Conclusions： It is possible that enriched MAM could increase [Ca^（2＋）]_m, and this increase has been found to be associated with increased apoptosis and compromised cytoplasmic maturation in oocytes from obese mice. This finding suggests a novel therapeutic target for obesity-induced oocyte defects.

Fatty Acid Synthase and Hormone-sensitive Lipase Expression in Liver Are Involved in Zinc-α2-glycoprotein-induced Body Fat Loss in Obese Mice

Objective To explore the effects of zinc-0t2-glycoprotein （ZAG） on body weight and body fat in high-fat-diet （HF1））-induced obesity in mice and the possible mechanism. Methods Thirty-six male mice were fed with standard food （SF） （n=9） and HFD （n=27）, respectively. Five weeks later, 9 mice fed with HFD were subjected to ZAG expression plasmid DNA transfection by liposome transfection method, and another 9 mice to negative control plasmid transfection. Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the effects of ZAG over-expression on body weight, body fat, serum biochemical indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of fatty acid synthase （FAS） and hormone sensitive lipase （HSL） in liver tissue were deterlnined by reverse transcription-polymerase chain reaction. Results Serum ZAG level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice （0.51±0.10 AU vs. 0.75±0.07 AU, P〈0.01）. Further statistical analysis demonstrated that ZAG level was negatively correlated with body weight （r =-0.56, P〈0.001）, epididymal fat mass （r=-0.67, P〈O. 001）, percentage of epididymal fat （r= 0.65, P〈0.001）, and increased weight （r= 0.57, P〈0.001） in simple SF- and HFD fed mice. ZAG over-expression in obese mice reduced body weight and the percentage of epididyreal fat. Furthermore, FAS mRNA expression decreased （P〈0.01） and HSL mRNA expression increased （P〈0.001） in the liver in ZAG over-expressing mice. Conclusions ZAG is closely related to obesity. Serum ZAG level is inversely correlated with body weight and percentage of body fat. The action of ZAG is associated with reduced FAS expression and increased HSL expression in the liver of obese mice.

2,4-Dinitrophenol Downregulates Genes for Diabetes and Fatty Liver in Obese Mice

Whether obesity is a disease or a risk factor of metabolic diseases including type 2 diabetes and fatty liver remains debating, we report here that a high-fat diet (HFD) alone or HFD-combined intramuscular injection with a high dose (1.2 mg/kg) of lipopolysaccharide (LPS) induces mouse peripheral noninflammatory obesity. In contrast, HFD-combined intraperitoneal injection with a low dose (0.25 mg/kg) of LPS induces mouse visceral low-grade inflammatory obesity. While the noninsulin-dependent diabetes mellitus (NIDDM) and nonalcoholic fatty liver disease (NAFLD)- related genes are globally upregulated in HFD + low-dose LPS mice, NIDDM and NAFLD genes are not extensively upregulated in HFD + high-dose LPS mice. The mitochondrial uncoupler 2,4-dini- trophenol (DNP) in the dosage of 16 mg/kg was found to exert a weight-reducing effect in obese mice by compromising NF-κB-primed inflammatory responses, thereby down regulating NIDDM and NAFLD genes. Conclusively, mouse visceral low-grade inflammatory obesity that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.

Functional Metabolomics Reveals that Astragalus Polysaccharides Improve Lipids Metabolism through Microbial Metabolite 2-Hydroxybutyric Acid in Obese Mice

Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic disorders.However,the underlying mechanisms are not well under-stood.Functional metabolomics is increasingly used to investigate systemic effects on the host by iden-tifying metabolites with particular functions.This study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides(APS)by adopting a functional metabolomics strategy.The effects of APS were determined in eight-week high-fat diet(HFD)-fed obese mice.Then,gas chromatography–time-of-flight mass spectrometry(GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues,and liquid chromatography–tandem mass spectrom-etry(LC–MS/MS)-based targeted metabolomics was performed.The potential functions of the metabo-lites were tested with in vitro and in vivo models of metabolic disorders.Our results first confirmed the metabolic benefits of APS in obese mice.Then,metabolomics analysis revealed that APS supplemen-tation reversed the HFD-induced metabolic changes,and identified 2-hydroxybutyric acid(2-HB)as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by APS.Further study indicated that 2-HB inhibited oleic acid(OA)-induced triglyceride(TG)accumula-tion.It was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 cells.Moreover,it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose(HFHS)-fed mice.In conclusion,our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation,which modulated lipid metabolism both in vitro and in vivo.Our results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.

Distribution of the P2X2 receptor and chemical coding in ileal enteric neurons of obese male mice(ob/ob)

AIM:To investigate the colocalization,density and profile of neuronal areas of enteric neurons in the ileum of male obese mice.METHODS:The small intestinal samples of male mice in an obese group(OG)(C57BL/6J ob/ob)and a control group(CG)(+/+)were used.The tissues were analyzed using a double immunostaining technique for immunoreactivity(ir)of the P2X2 receptor,nitric oxide synthase(NOS),choline acetyl transferase(ChAT)and calretinin(Calr).Also,we investigated the density and profile of neuronal areas of the NOS-,ChAT-and Calrir neurons in the myenteric plexus.Myenteric neurons were labeled using an NADH-diaphorase histochemical staining method.RESULTS:The analysis demonstrated that the P2X2receptor was expressed in the cytoplasm and in the nuclear and cytoplasmic membranes only in the CG.Neuronal density values(neuron/cm2)decreased 31%(CG:6579±837;OG:4556±407)and 16.5%(CG:7796±528;OG:6513±610)in the NOS-ir and calretininir neurons in the OG,respectively(P<0.05).Density of ChAT-ir(CG:6200±310;OG:8125±749)neurons significantly increased 31%in the OG(P<0.05).Neuron size studies demonstrated that NOS,ChAT,and Calr-ir neurons did not differ significantly between the CG and OG groups.The examination of NADH-diaphorase-positive myenteric neurons revealed an overall similarity between the OG and CG.CONCLUSION:Obesity may exert its effects by promoting a decrease in P2X2 receptor expression and modifications in the density of the NOS-ir,ChAT-ir and CalR-ir myenteric neurons.

Anti-insulin resistant effect of ferulic acid on high fat diet-induced obese mice

Objective: To evaluate the insulin sensitivity action of ferulic acid(FA) in skeletal muscle and hypothalamus of high-fat diet(HFD)-induced obese mice. Methods: Obese mouse model was induced by HFD(45 kcal% lard fat) for 16 weeks. After 8 weeks of HFD feeding, these obese mice were orally treated with FA at doses of 25 and 50 mg/kg/day for 8 weeks. At the end of all treatments, the epididymal fat, pancreas, skeletal muscle and hypothalamus were removed for biochemical parameter and protein expression examinations. Results: FA treatment significantly decreased leptin level in fat tissue and insulin level in pancreas(P < 0.05). Interestingly, obese mice treated with FA increased the protein expressions of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and phosphorylated-protein kinase B in both muscle and brain(P < 0.05). The phosphorylations of adenosine monophosphate-activated protein kinase and acetyl-CoA carboxylase in muscle, and leptin receptor protein in hypothalamus were also increased(P < 0.05). The pancreatic islets histology showed smaller size in obese mice treated with FA compared to untreated obese mice. Conclusions: These findings indicate the beneficial effect of FA in improving insulin resistance in HFD-induced obese mice. These effects are probably mediated via modulating the insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B or adenosine monophosphate-activated protein kinase pathways.

Long-Term Treatment with an Herbal Formula MCC Ameliorates Obesity-Associated Metabolic Dysfunction in High Fat Diet-Induced Obese Mice: A Comparative Study among MCC and Various Combinations of Its Constituents

Obesity has been found to be associated with increased incidence of various metabolic disorders. Anti-obesity interventions are therefore urgently needed. An earlier study has demonstrated that treatment with an herbal formula MCC, which comprises the fruit of Momordica charantia (MC), the pericarpium of Citri reticulate (CR) and L-carnitine (CA), reduced the weight gain in high fat diet (HFD)-fed mice. In the present study, we investigated the effect of long-term treatment with MCC (6 g/kg/day × 40 doses) and various combinations of its constituents in HFD-fed female ICR mice. Body weight change was monitored during the course of the experiment. Total and differential adiposity, plasma lipid contents, metabolic enzyme activities and mitochondrial coupling efficiency in skeletal muscle were measured. Glucose homeostasis was also assessed. Results showed that HFD increased the body weight, total and differential adiposity, and plasma lipid contents as well as impaired metabolic status in skeletal muscle and glucose homeostasis. MCC and all combinations of its constituents reduced the weight gain in HFD-fed mice, which was accompanied with an improvement on glucose homeostasis. While MC, CA and CR independently suppressed the HFD-induced weight gain in mice, MC seems to be the most effective in weight reduction, all of which correlated with the induction of mitochondrial uncoupling in skeletal muscle. Only CA and CR, but not MC, significantly reduced the total adiposity and visceral adiposity as well as plasma cholesterol level. However, the two component combinations, MC + CR and MC + CA, decreased the degree of visceral adiposity and plasma cholesterol level, respectively. MCC treatment at 1.5 g/kg (but not a higher dose of 6 g/kg) suppressed visceral adiposity and induced mitochondrial uncoupling in skeletal muscle in HFD-fed mice. The finding suggests that MCC may offer a promising prospect for ameliorating the diet-induced obesity and metabolic disorders in humans.