Sesamol improves inflammation and insulin resistance in adipose tissue of obese mice by regulating macrophage polarization / 中国临床药理学与治疗学

AIM: To investigate whether sesamol can improve inflammation and insulin resistance in adipose tissue of obese mice by regulating macrophage polarization. METHODS: An obese animal model was established in mice by inducing obesity with high-fat diet. The obese mice were administrated with sesamol (100 mg/kg) for 8 weeks. The mice were sacrificed after the intraperitoneal glucose tolerance test and insulin tolerance test, and the plasma lipid and insulin levels were measured. The expression of P-AKT and P-JNK in adipose tissue of epididymis was detected by Western blotting. F4/80 and Cd11c immunohistochemistry and immunofluorescence staining were performed on the adipose tissue sections. The mRNA expression of cytokines and chemokines in adipose tissue was measured by Real-time fluorescence quantitative PCR. RESULTS: Sesamol treatment reduced body weight and lipid level of obese mice, improved glucose tolerance and insulin resistance. In sesamol treated group, macrophage infiltration in adipose tissue was decreased, P-AKT expression was enhanced, P-JNK expression was reduced, mRNA expression of M1 type of macrophage markers (Cd11c, iNOS, TNF-α and IL-6) was down-regulated, mRNA expression of M2 type markers (chi3l3, Arg1 and Mgl1) was up-regulated. CONCLUSION: Sesamol can alleviate inflammation and insulin resistance in adipose tissue of obese mice. These effects may be associated with inhibition of JNK signal pathway and improvement of polarization imbalance of macrophages in adipose tissue.

Study of betulinic acid to improve non-alcoholic fatty liver disease / 中华内分泌代谢杂志

Objective To explore the effect of betulinic acid on NAFLD and its mechanism. Methods We used the high-fat diet animal models, with or without feeding the standard chow diet containing betulinic acid for 2 months. During this period, the body weight was monitored regularly and metabolism cage was used to monitor the energy metabolism of the animals. After killing the mice, molecular biological analysis was performed on serum and tissue related to liver. Results In diet induced obese mice animal experiments, the mice body weight had been reduced and NAFLD had been improved significantly by betulinic acid. The various indexs of serum and liver tissue had also been significantly improved. The metabolic rate increased significantly. Fatty acid synthase gene and protein levels were significantly lower. Furthermore, FAS activity was significantly lower than the control mice. Liver FAS activity of the high fat mice and the high fat mice treated with betulinic acid were (1873.6 ± 85.7) and (1181.6 ± 85.7) pmol NADPH/ min/ mg protein, respectively. Conclusion Betulinic acid inhibited FAS at expression and activity level, and improved lipid deposition in liver.

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

OBJECTIVES@#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 mRNA 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.

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

Objectives 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 mRNA 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.

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 receptor γ (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 HFD-induced obese mice.

Roots extracts of Adenophora triphylla var. japonica improve obesity in 3T3-L1 adipocytes and high-fat diet-induced obese mice

OBJECTIVE@#To investigate the anti-obesity activity and the action mechanism of the roots of Adenophora triphylla var. japonica extract (ATE) in high-fat diet (HFD)-induced obese mice and 3T3-L1 adipocytes.@*METHODS@#The roots of Adenophora triphylla were extracted with 70% ethanol. To demonstrate the compounds, linoleic acid was analyzed by using gas chromatography; and the anti-obesity effects and possible mechanisms of ATE were examined in 3T3-L1 adipocytes and HFD-induced obese mice.@*RESULTS@#Treatment with ATE inhibited the lipid accumulation without cytotoxicity in 3T3-L1 adipocytes. Furthermore, 200 and 400 mg/kg ATE treatment significantly decreased the body weight gain, white adipose tissues (WATs) weight and plasma triglyceride level, while 100 and 200 mg/kg ATE treatment increased the plasma high-density lipoprotein cholesterol level in the HFD-induced obese mice, as compared with the HFD group. Treatment with 200 and 400 mg/kg ATE also lowered the size of adipocytes in adipose tissue and reduced the lipid accumulation in liver. ATE treatment showed significantly lower expression level of adipogenesis-related proteins, such as peroxisome proliferator-activated receptor γ, fatty acid binding protein (aP2), fatty acid synthase in 3T3-L1 adipocytes; and furthermore, decreased peroxisome proliferator-activated receptor γ, aP2, fatty acid synthase, sterol regulatory element binding protein-1c, and lipoprotein lipase mRNA expression levels in WAT of the HFD-induced obese mice.@*CONCLUSIONS@#These results suggested that the ATE has an anti-obesity effect, which may be elicited by regulating the expression of adipogenesis and lipogenesis-related genes and proteins in adipocytes and WAT of the HFD-induced obese mice.

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 receptor γ(PPAR γ), 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 HFD-induced obese mice.

Anti-Obesity Effects on Unripe Rubus coreanus Miquel Extract in High Fat Diet-Induced Obese Mice.

Aims: The objective of the present study was to evaluate the anti-obesity effects of unripe Rubus coreanus Miquel (uRC) in 3T3-L1 adipocytes and body weight, epididymal fat and perirenal fat weight, and lipid profiles in diet-induced obese (DIO) C57BL/6 mice. Methodology: The lipid accumulation in 3T3-L1 adipocytes was carried out Oil Red O staining. And uRC (50 and 100 mg/kg/day) were orally administered for 90 days from the day of feeding with high fat diet (HFD). The serum total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL)-cholesterol and low density lipoprotein(LDL)-cholesterol and glucose levels were measured using Alere cholesterol LDXⓇ system. And the serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen(BUN) and creatinine levels were measured using the respective kits. Results: Our results indicated that treatment with uRC dose-dependently inhibited lipid accumulation in 3T3-L1 adipocytes. Moreover, after oral administration for 12 weeks, uRC (50 and 100mg/kg/day) extract produced a significant decrease in the serum total cholesterol (TC), lowdensity lipoprotein (LDL) cholesterol, glucose and glutamic-oxaloacetic transaminase (GOT) levels of HFD-induced obese mice. Similarly, uRC extract elevated serum high density lipoprotein (HDL) cholesterol. These results suggest that uRC extract may be a useful resource for the management of obesity. Conclusion: These results suggest that uRC extract may be a useful resource for the management of obesity.

Roots extracts of Adenophora triphylla var. japonica improve obesity in 3T3-L1 adipocytes and high-fat diet-induced obese mice

Objective: To investigate the anti-obesity activity and the action mechanism of the roots of Adenophora triphylla var. japonica extract (ATE) in high-fat diet (HFD)-induced obese mice and 3T3-L1 adipocytes. Methods: The roots of Adenophora triphylla were extracted with 70% ethanol. To demonstrate the compounds, linoleic acid was analyzed by using gas chromatography; and the anti-obesity effects and possible mechanisms of ATE were examined in 3T3-L1 adipocytes and HFD-induced obese mice. Results: Treatment with ATE inhibited the lipid accumulation without cytotoxicity in 3T3-L1 adipocytes. Furthermore, 200 and 400 mg/kg ATE treatment significantly decreased the body weight gain, white adipose tissues (WATs) weight and plasma triglyceride level, while 100 and 200 mg/kg ATE treatment increased the plasma high-density lipoprotein cholesterol level in the HFD-induced obese mice, as compared with the HFD group. Treatment with 200 and 400 mg/kg ATE also lowered the size of adipocytes in adipose tissue and reduced the lipid accumulation in liver. ATE treatment showed significantly lower expression level of adipogenesis-related proteins, such as peroxisome proliferator-activated receptor γ, fatty acid binding protein (aP2), fatty acid synthase in 3T3-L1 adipocytes; and furthermore, decreased peroxisome proliferator-activated receptor γ, aP2, fatty acid synthase, sterol regulatory element binding protein-1c, and lipoprotein lipase mRNA expression levels in WAT of the HFD-induced obese mice. Conclusions: These results suggested that the ATE has an anti-obesity effect, which may be elicited by regulating the expression of adipogenesis and lipogenesis-related genes and proteins in adipocytes and WAT of the HFD-induced obese mice.

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 receptor γ(PPAR γ), 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 HFD-induced obese mice.

Effects of Voluntary Running-Wheel Exercise on Insulin, Oxidative Stress and Advanced Glycation End Products in High-Fat Diet-Induced Obese Mice

BACKGROUND: Obesity-induced insulin resistance is an important risk factor for type 2 diabetes and cardiovascular disease. However, as potential mechanisms of increased insulin, how oxidative stress (OS) advanced glycation end-products (AGEs) can be changed through exercise is not fully understood. METHODS: A total of 36 C57BL/6 mice were fed either a high-fat diet (HFD; n=19) or chow diet (Chow; n=17) for 7 weeks. The two groups were then divided into voluntary running wheel exercise or no-exercise subgroups each, and the four groups were provided with another 8 weeks of intervention: 1) HFD+exercise (HE; n=11), 2) HFD+no exercise (HN; n=8), 3) Chow+exercise (CE; n=8), and 4) Chow+no exercise (CN; n=9). Body weight, fasting insulin level, and AGEs were measured before and after intervention. ANOVA and Pearson's multiple correlation coefficients were used for statistical analysis using SPSS statistics software version 20.0. RESULTS: The HE group showed significantly greater weight reduction (P<0.01), while CE and CN did not show significantly different weight reductions between each other. Also, the fasting insulin level was significantly lower in the HE group than in the HN group. The 7-week HFD intervention significantly increased OS and AGEs. However, 8 weeks of exercise did not significantly change OS and AGEs among the groups. CONCLUSION: The findings of the current study suggest that OS and AGEs may not be related to the pathway of exercise-induced improvement in insulin levels in obese mice.

Inhibitory effects of Doenjang, Korean traditional fermented soybean paste, on oxidative stress and inflammation in adipose tissue of mice fed a high-fat diet

BACKGROUND/OBJECTIVES: Doenjang, Korean traditional fermented soybean paste has been reported to have an anti-obesity effect. Because adipose tissue is considered a major source of inflammatory signals, we investigated the protective effects of Doenjang and steamed soybean on oxidative stress and inflammation in adipose tissue of diet-induced obese mice. MATERIALS/METHODS: Male C57BL/6J mice were fed a low fat diet (LF), a high-fat diet (HF), or a high-fat containing Doenjang diet (DJ) or a high-fat containing steamed soybean diet (SS) for 11 weeks. RESULTS: Mice fed a DJ diet showed significantly lower body and adipose tissue weights than those in the HF group. Although no significant differences in adipocyte size and number were observed among the HF diet-fed groups, consumption of Doenjang alleviated the incidence of crown-like structures in adipose tissue. Consistently, we observed significantly reduced mRNA levels of oxidative stress markers (heme oxygenase-1 and p40phox), pro-inflammatory adipokines (tumor necrosis factor alpha and macrophage chemoattractant protein-1), macrophage markers (CD68 and CD11c), and a fibrosis marker (transforming growth factor beta 1) by Doenjang consumption. Gene expression of anti-inflammatory adipokine, adiponectin was significantly induced in the DJ group and the SS group compared to the HF group. The anti-oxidative stress and anti-inflammatory effects observed in mice fed an SS diet were not as effective as those in mice fed a DJ diet, suggesting that the bioactive compounds produced during fermentation and aging may be involved in the observed health-beneficial effects of Doenjang. CONCLUSIONS: Doenjang alleviated oxidative stress and restored the dysregulated expression of adipokine genes caused by excess adiposity. Therefore, Doenjang may ameliorate systemic inflammation and oxidative stress in obesity via inhibition of inflammatory signals of adipose tissue.

Effects of resveratrol on the insulin signaling pathway of obese mice

The present study was conducted to investigate the effects of resveratrol on the insulin signaling pathway in the liver of obese mice. To accomplish this, we administered resveratrol to high fat diet-induced obese mice and examined the levels of protein phosphorylation in the liver using an antibody array. The phosphorylation levels of 10 proteins were decreased in the high fat diet and resveratrol (HFR) fed group relative to the levels in the high fat diet (HF) fed group. In contrast, the phosphorylation levels of more than 20 proteins were increased in the HFR group when compared with the levels of proteins in the HF group. Specifically, the phosphorylation levels of Akt (The308, Tyr326, Ser473) were restored to normal by resveratrol when compared with the levels in the HF group. In addition, the phosphorylation levels of IRS-1 (Ser636/Ser639), PI-3K p85-subunit alpha/gamma(Tyr467/Tyr199), PDK1 (Ser241), GSK-3alpha (S21) and GSK-3 (Ser9), which are involved in the insulin signaling pathway, were decreased in the HF group, whereas the levels were restored to normal in the HFR group. Overall, the results show that resveratrol restores the phosphorylation levels of proteins involved in the insulin signaling pathway, which were decreased by a high fat diet.

The anti-obesity effect of Lethariella cladonioides in 3T3-L1 cells and obese mice

The aim of this study was to investigate whether a water extract of L. cladonioides (LC) has an anti-obesity effect in 3T3-L1 cells and obese mice. Treatment of differentiated 3T3-L1 adipocytes with LC caused a significant increase in glycerol release and reduced the protein expression of the adipogenic transcription factors, PPARgamma and C/EBPalpha. In an animal model, obese mice were artificially induced by a high fat diet for 10 weeks. Experimental groups were treated with LC (100 mg/kg/day) by gavage for the next 10 weeks. At the end of experiment, the body weight of the LC group mice was reduced by 14.2% compared to the high fat diet (HFD) group. The treatment also decreased liver (31.0%), epididymal (18.0%) and retroperitoneal (19.3%) adipose tissue, and kidney (6.7%) weights, respectively, compared with those of the HFD group. LC prevented diet-induced increases in the serum level of TC (22.6%), TG (11.6%), and glucose (35.0%), respectively, compared with the HFD group. However, the HDL-C level was higher in the LC group (26.1%) than the HFD group. The results of this study thus suggest that LC suppressed lipid accumulation and expression of adipogenic transcription factors, and increased the amount of glycerol release. LC also indicated an anti-obese and anti-hyperlipidemic effect.