绿茶和红茶多酚对大鼠脂肪分化相关基因表达影响的比较研究

目的:比较绿茶多酚(GTP)和红茶多酚(BTP)抗肥胖作用及其分子机制。方法:将实验大鼠分为空白对照组,高脂饲料+GTP组,高脂饲料+BTP组,高脂饲料组,定期检测体重,喂饲3个月后,观察脂肪组织和血脂水平变化,并提取附睾脂肪组织,应用RT-PCR技术观察与脂肪细胞分化相关的基因pref-1,aP2,TNF-α,瘦素,PPAR-γ,C/EBP-α在mRNA水平的表达。结果:GTP和BTP均能明显降低体重,减少脂肪。同时,GTP和BTP均能显著地抑制脂肪细胞特殊标记物aP2,TNF-α,瘦素,但两者之间无统计学差异。此外,GTP还上调前脂肪细胞标记物pref-1,且下调转录因子PPAR-γ。结论:GTP和BTP均可通过调节与脂肪细胞分化相关的基因,逆转脂肪细胞的分化,达到抗肥胖的作用,且GTP抗肥胖作用强于BTP。     

Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice

Nonalcoholic fatty liver disease (NAFLD), along with obesity, is increasing world-wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS) on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver.     

Green tea extract reduces blood pressure,inflammatory biomarkers,and oxidative stress and improves parameters associated with insulin resistance in obese,hypertensive patients

Green tea (GT) consumption is known to be associated with enhanced cardiovascular and metabolic health. The purpose of this study is to examine the hypothesis that supplementation with GT alters insulin resistance and associated cardiovascular risk factors in obese, hypertensive patients. In a double-blind, placebo-controlled trial, 56 obese, hypertensive subjects were randomized to receive a daily supplement of 1 capsule that contained either 379 mg of GT extract (GTE) or a matching placebo, for 3 months. At baseline and after 3 months of treatment, the anthropometric parameters, blood pressure, plasma lipid levels, glucose levels, creatinine levels, tumor necrosis factor α levels, C-reactive protein levels, total antioxidant status, and insulin levels were assessed. Insulin resistance was evaluated according to the homeostasis model assessment–insulin resistance protocol. After 3 months of supplementation, both systolic and diastolic blood pressures had significantly decreased in the GTE group as compared with the placebo group (P < .01). Considerable (P < .01) reductions in fasting serum glucose and insulin levels and insulin resistance were observed in the GTE group when compared with the placebo group. Serum tumor necrosis factor α and C-reactive protein were significantly lower, whereas total antioxidant status increased in the GTE group compared with the placebo (P < .05). Supplementation also contributed to significant (P < .05) decreases in the total and low-density lipoprotein cholesterol and triglycerides, but an increase in high-density lipoprotein cholesterol. In conclusion, daily supplementation with 379 mg of GTE favorably influences blood pressure, insulin resistance, inflammation and oxidative stress, and lipid profile in patients with obesity-related hypertension.     

Silk peptides inhibit adipocyte differentiation through modulation of the Notch pathway in C3H10T1/2 cells

Silk protein is a biocompatible material that has been used in many biotechnological applications and exhibits body fat-lowering effects. Recent studies have shown that silk peptides increase expression of osteogenic markers in osteoblast-like cells. Because osteogenic and adipogenic differentiation from common mesenchymal progenitor cells are inverse processes and often regulated reciprocally, we hypothesized that silk peptides might suppress adipocyte differentiation. We therefore endeavored to evaluate the effects of silk peptides on adipocyte differentiation in C3H10T1/2 cells. We find that silk peptides inhibit lipid accumulation and morphological differentiation in these cells. Molecular studies show that silk peptides block expression of adipocyte-specific genes such as peroxisome proliferator-activated receptor γ and its targets, including aP2, Cd36, CCAAT enhancer binding proteinα. Silk peptides appear to inhibit adipogenesis by suppression of the Notch pathway, repressing the Notch target genes Hes-1 and Hey-1. In addition, these peptides inhibit endogenous Notch activation, as shown by a reduction in generation of Notch intracellular domain. N-[N-(3.5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butylester, compound E, and WPE-III-31C, which are all known Notch signaling inhibitors, block adipocyte differentiation to an extent similar to silk peptides. Together, our data demonstrate that silk peptides can modulate adipocyte differentiation through inhibition of the Notch signaling and further suggest potential future strategies for treating obesity and its related metabolic diseases.     

Dietary fat level affects tissue iron levels but not the iron regulatory gene HAMP in rats

Because dietary fats affect the regulation and use of body iron, we hypothesized that iron regulatory and transport genes may be affected by dietary fat. A model of early-stage I to II, nonalcoholic fatty liver was used in which rats were fed standard (35% energy from fat) or high-fat (71% energy from fat) liquid diets with normal iron content (STD/HF groups). In addition, intraperitoneal injections of iron dextran were given to iron-loaded (STD+/HF+ groups) and iron-deficient diets to STD−/HF− groups. Plasma osmolality, hemoglobin level, and mean corpuscular hemoglobin concentration were increased in all STD diet groups compared with all HF diet groups. Plasma iron and transferrin saturation were affected by an interaction between dietary fat and iron. They were high in the STD group (normal iron) compared with their respective HF group. Similarly, this group also showed a 4-fold increase in the messenger RNA expression of the hepatic hemochromatosis gene. Spleen iron was high in the iron-loaded STD+ group compared with all other groups. Hepatic iron and messenger RNA expression of peroxisome proliferator–activated receptor-γ, CCAAT/enhancer binding protein α, interleukin-6, and iron transport genes (transferrin receptor 2, divalent metal transporter 1 iron-responsive element, and divalent metal transporter 1 non–iron-responsive element) were increased, whereas tumor necrosis factor α was decreased in the HF diet groups. The expression of iron regulatory gene HAMP was not increased in the HF diet groups. Iron regulatory and transport genes involved in cellular and systemic iron homeostasis may be affected by the macronutrient composition of the diet.     

Corn gluten hydrolysate and capsaicin have complimentary actions on body weight reduction and lipid-related genes in diet-induced obese rats

The aim of this study was to test the hypothesis that a combination of corn gluten hydrolysate (CGH) and capsaicin may have an additive or synergistic effect on body weight reduction. For 13 weeks, male Sprague-Dawley rats were provided a diet to induce obesity. Afterward, the rats were randomly divided into 5 dietary groups: the normal control (n = 5), the high-fat control (n = 8), the high-fat diet (HFD) containing 35% CGH (n = 7), the HFD containing 0.02% capsaicin (HF-P) (n = 8), and the HFD containing both CGH and capsaicin (HF-CP) (n = 7) for an additional 4 weeks. Administration of CGH plus capsaicin, along with a HFD, led to significant decreases in body weight, fat mass, lipids in the liver, and plasma leptin as well as increases in plasma adiponectin. The pattern of gene expression was different in each target organ. In the liver, up-regulation of peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1α, and acyl-coenzyme A oxidase was found in the HF-CP group. In contrast, down-regulation of peroxisome proliferator-activated receptor γ was found in both the HFD containing 35% CGH and HF-CP groups. In skeletal muscle, up-regulation of insulin receptor and uncoupling protein 3 was found in the HF-P group only, whereas up-regulation of the glucose transporter 4 gene was observed in both the HF-CP and HF-P groups. In adipose tissue, up-regulation of peroxisome proliferator-activated receptor γ and hormone-sensitive lipase was only found in the HF-CP group. In summary, this study suggests that CGH and capsaicin perform complementary actions on food intake, lipid metabolism, and insulin sensitivity by a coordinated control of energy metabolism in the liver, adipose tissue, and skeletal muscle, thus exerting an additive effect on body weight reduction.     

Feed withdrawal abate regimens lipodystrophy and metabolic syndrome symptoms,such as glucose tolerance,are associated with the diameter of retroperitoneal adipocytes in rats

Adipocyte numbers were increased by feed withdrawal (FW) regimens in cattle; thus, the effect of FW regimens was studied in male Wistar and fa/fa obese rats, as models for humans, in 2 completely randomized design experiments to abate lipodystrophy and progression of metabolic syndrome symptoms. The hypothesis was that application of FW regimens could alter adipose tissue cellularity, adipocyte size, and affect area under the curve (AUC) during glucose tolerance tests. Objectives were to determine associations among retroperitoneal and inguinal adipose tissue adipocyte number, diameter, and AUC, as affected by fortnightly or a single (at age 50 days) 24-hour FW regimen. Adipocyte marker peroxisome proliferator–activated receptor γ expression was elevated (P = .054) in the retroperitoneal tissue of fa/fa obese rats in the fortnightly FW treatment because of a 13% increase in tissue cell density (cells per gram; P = .13). Average cell diameter in retroperitoneal adipose and AUC were negatively corelated. Regression analyses after including the square of average cell diameter indicated that average retroperitoneal adipocyte diameter (between 65 and 135 μm) and the AUC were related in a quadratic manner (R² = 0.14; n = 49; P = .03) for Wistar rats. Cell number of the inguinal and retroperitoneal adipocytes tended to be positively corelated (r = 0.24; P = .09 and r = 0.26; P = .07, n = 49, respectively) to the AUC and are indexes of adiposity. Results suggest that maintenance of retroperitoneal adipocytes at appropriate diameters may control progression of metabolic syndrome symptoms such as glucose tolerance.     

Supplementation of Korean fermented soy paste doenjang reduces visceral fat in overweight subjects with mutant uncoupling protein-1 allele

The purpose of this study was to examine the hypothesis that the antiobesity effect of doenjang, a Korean fermented soy paste is different between the mutant and the wild-type alleles of a polymorphism upstream of the uncoupling protein-1 (UCP-1) gene in overweight subjects. In our randomized, double-blind, placebo-controlled trial, a total of 51 subjects with a body mass index of 23 kg/m² or greater and a waist-to-hip ratio of 0.90 or greater for men or 0.85 or greater for women were randomly assigned to take 9.9 g/d of either a placebo or doenjang for 12 weeks. The relative frequency of the mutant G allele of the UCP-1 polymorphism was 0.60 in the placebo group and 0.62 in the doenjang group. Supplementation of doenjang had no significant effect on the visceral fat area compared with that of the placebo group, but there was a significantly reduced amount of visceral fat in subjects with the G allele of UCP-1 polymorphism. Doenjang supplementation was found to significantly increase the free fatty acid concentration in subjects with both the A allele and the G allele. There was a significant association between visceral fat and age in study subjects with both the wild-type and mutant alleles of the UCP-1 gene. Doenjang supplementation significantly reduced visceral fat and increased the free fatty acid concentrations in subjects with the G allele of the UCP-1 polymorphism, which suggests that doenjang may be related to increased free fatty acid levels caused by elevated lipolysis in these subjects.     

Cooked rice prevents hyperlipidemia in hamsters fed a high-fat/cholesterol diet by the regulation of the expression of hepatic genes involved in lipid metabolism

Rice has many health-beneficial components for ameliorating obesity, diabetes, and dyslipidemia. However, the effect of cooked rice as a useful carbohydrate source has not been investigated yet; so we hypothesized that cooked rice may have hypolipidemic effects. In the present study, we investigated the effect of cooked rice on hyperlipidemia and on the expression of hepatic genes involved in lipid metabolism. Golden Syrian hamsters were divided into 2 groups and fed a high-fat (15%, wt/wt)/cholesterol (0.5%, wt/wt) diet supplemented with either corn starch (HFD, 54.5% wt/wt) or cooked rice (HFD-CR, 54.5% wt/wt) as the main carbohydrate source for 8 weeks. In the HFD-CR group, the triglyceride and total cholesterol levels in the serum and liver were decreased, and the total lipid, total cholesterol, and bile acid levels in the feces were increased, compared with the HFD group. In the cooked-rice group, the messenger RNA and protein levels of 3-hydroxy-3-methylglutaryl CoA reductase were significantly downregulated; and the messenger RNA and protein levels of the low-density lipoprotein receptor and cholesterol-7α-hydroxylase were upregulated. Furthermore, the expressions of lipogenic genes such as sterol response element binding protein-1, fatty acid synthase, acetyl CoA carboxylase, and stearoyl CoA desaturase-1 were downregulated, whereas the β-oxidation related genes (carnitine palmitoyl transferase-1, acyl CoA oxidase, and peroxisome proliferator-activated receptor α) were upregulated, in the cooked-rice group. Our results suggest that the hypolipidemic effect of cooked rice is partially mediated by the regulation of hepatic genes involved in lipid metabolism, which results in the suppression of cholesterol and fatty acid synthesis and the enhancement of cholesterol excretion and fatty acid β-oxidation.     

Soluble extract of soybean fermented with Aspergillus oryzae GB107 inhibits fat accumulation in cultured 3T3-L1 adipocytes

BACKGROUND/OBJECTIVESThis study was conducted to investigate the effects of fermented soybean (FS) extract on adipocyte differentiation and fat accumulation using cultured 3T3-L1 adipocytes.MATERIALS/METHODS3T3-L1 adipocytes were treated with FS and nonfermented soybean (NFS) extract during differentiation for 10 days in vitro. Oil red O staining was performed and glycerol-3-phosphate dehydrogenase (GPDH) activity was measured for analysis of fat accumulation. Expressions of adipogenic genes were measured.RESULTSSoluble extract of soybean fermented with Aspergillus oryzae GB107 contained higher levels of low-molecular-weight protein than conventional soybean protein did. FS extract (50 µg/ml) inhibited adipocyte differentiation and fat accumulation during differentiation of 3T3-L1 preadipocytes for 10 days in vitro. Significantly lower GPDH activity was observed in differentiated adipocytes treated with the FS extract than those treated with NFS extract. Treatment with FS extract resulted in decreased expression levels of leptin, adiponectin, and adipogenin genes, which are associated with adipogenesis.CONCLUSIONSThis report is the first to demonstrate that the water-soluble extract from FS inhibits fat accumulation and lipid storage in 3T3-L1 adipocytes. Thus, the soybean extract fermented with A. oryzae GB107 could be used to control lipid accumulation in adipocytes.     

Dietary intervention with vitamin D,calcium, and whey protein reduced fat mass and increased lean mass in rats

The aim of the current study was to determine the effects and the mechanisms of inclusion of dietary whey protein, high calcium, and high vitamin D intake with either a high-sucrose or high-fat base diets on body composition of rodents. Male Wistar rats were assigned to either no whey protein, suboptimal calcium (0.25%), and vitamin D (400 IU/kg) diet (LD), or a diet containing whey protein, high calcium (1.5%), and vitamin D (10 000 IU/kg) diet (HD), and either high-fat (40% of energy) or high-sucrose (60%) base diets for 13 weeks. Liver tissue homogenates were used to determine [¹⁴C]glucose and [¹⁴C]palmitate oxidation. mRNA expression of enzymes related to energy metabolism in liver, adipose, and muscle, as well as regulators of muscle mass and insulin receptor was assessed. The results demonstrated that there was reduced accumulation of body fat mass (P = .01) and greater lean mass (P = .03) for the HD- compared to LD-fed group regardless of the background diet. There were no consistent differences between the LD and HD groups across background diets in substrate oxidation and mRNA expression for enzymes measured that regulate energy metabolism, myostatin, or muscle vascular endothelial growth factor. However, there was an increase in insulin receptor mRNA expression in muscle in the HD compared to the LD groups. In conclusion, elevated whey protein, calcium, and vitamin D intake resulted in reduced accumulation of body fat mass and increased lean mass, with a commensurate increase in insulin receptor expression, regardless of the level of calories from fat or sucrose.     

Chitooligosaccharide ameliorates diet-induced obesity in mice and affects adipose gene expression involved in adipogenesis and inflammation

Chitooligosaccharide (CO) has been reported to have potential antiobestic effects in a few studies, but the antiobesity properties of CO and its related mechanisms in models of dietary obesity remain unclear. We investigated the effect of CO on body weight gain, size of adipocytes, adipokines, and lipid profiles in high-fat (HF) diet-induced obese mice and on the gene expression in adipose tissue using a complementary DNA microarray approach to test the hypothesis that CO supplementation would alleviate HF diet-induced obesity by the alteration of adipose tissue-specific gene expression. Male C57BL/6N mice were fed a normal diet (control), HF diet, or CO-supplemented HF diet (1% or 3%) for 5 months. Compared with the HF diet mice, mice fed the 3% CO-supplemented diet gained 15% less weight but did not display any change in food and energy intake. Chitooligosaccharide supplementation markedly improved serum and hepatic lipid profiles. Histologic examination showed that epididymal adipocyte size was smaller in mice fed the HF + 3% CO. Microarray analysis showed that dietary CO supplementation modulated adipogenesis-related genes such as matrix metallopeptidases 3, 12, 13, and 14; tissue inhibitor of metalloproteinase 1; and cathepsin k in the adipose tissues. Twenty-five percent of the CO-responsive genes identified are involved in immune responses including the inflammatory response and cytokine production. These results suggest that CO supplementation may help ameliorate HF diet-induced weight gain and improve serum and liver lipid profile abnormalities, which are associated, at least in part, with altered adipose tissue gene expression involved in adipogenesis and inflammation.     

Effects of green tea or Sasa quelpaertensis bamboo leaves on plasma and liver lipids, erythrocyte Na efflux, and platelet aggregation in ovariectomized rats

This study was conducted to investigate the effects of Sasa quelpaertensis bamboo and green tea on plasma and liver lipids, platelet aggregation, and erythrocyte membrane Na channels in ovariectomized (OVX) rats. Thirty female rats were OVX, and ten female rats were sham-operated at the age of 6 weeks. The rats were divided into four groups at the age of 10 weeks and fed the experiment diets: sham-control, OVX-control, OVX-bamboo leaves (10%), or OVX-green tea leaves (10%) for four weeks. Final body weight increased significantly in the OVX groups compared with that in the sham-control, whereas body weight in the OVX-green tea group decreased significantly compared with that in the OVX-control (P < 0.01). High density lipoprotein (HDL)-cholesterol level decreased in all OVX groups compared with that in the sham-control rats (P < 0.05) but without a difference in plasma total cholesterol. Plasma triglycerides in the OVX-green tea group were significantly lower than those in the sham-control or OVX-control group (P < 0.05). Liver triglycerides increased significantly in the OVX-control compared with those in the sham-control (P < 0.01) but decreased significantly in the OVX-green tea group compared with those in the OVX-control or OVX-bamboo group (P < 0.01). Platelet aggregation in both maximum and initial slope tended to be lower in all OVX rats compared with that in the sham-control rats but was not significantly different. Na-K ATPase tended to increase and Na-K cotransport tended to decrease following ovariectomy. Na-K ATPase decreased significantly in the OVX-green tea group compared with that in the OVX-control group (P < 0.01), and Na-K cotransport increased significantly in the OVX-bamboo and OVX-green tea groups compared with that in the OVX-control (P < 0.05). Femoral bone mineral density tended to be lower in OVX rats than that in the sham-control, whereas the green tea and bamboo leaves groups recovered bone density to some extent. The results show that ovariectomy caused an increase in body weight and liver triglycerides, and that green tea was effective for lowering body weight and triglycerides in OVX rats. Ovariectomy induced an increase in Na efflux via Na-K ATPase and a decrease in Na efflux via Na-K cotransport. Furthermore, consumption of green tea and bamboo leaves affected Na efflux channels, controlling electrolyte and body water balance.     

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 p40^phox), 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.