Ficus carica Leaf Extract Modulates the Lipid Profile of Rats Fed with a High‐Fat Diet through an Increase of HDL‐C

Ficus carica has been traditionally used for the treatment of several metabolic syndrome‐related health problems. It was the objective of this study to investigate the preventive effects of a Ficus carica (FC) leaf extract on hyperlipidemia in high fat diet (HFD)‐induced obese male rats. Male Sprague–Dawley rats (180 – 200 g) were fed with a regular diet, HFD or a HFD + oral treatment of either 50 mg/kg or 100 mg/kg of FC or 30 mg/kg pioglitazone for six weeks. A range of parameters was evaluated including body weight development, plasma levels of total cholesterol, triglycerides (TG), low‐density‐lipoprotein cholesterol, high‐density lipoprotein cholesterol (HDL‐C), adiponectin, leptin, glucose, insulin, interleukin‐6 (IL‐6), atherogenic index (AI) and the coronary risk index (CRI). FC significantly lowered TG and IL‐6 levels and elevated HDL cholesterol (p < 0.05). The effects of FC on lipid parameters were more pronounced than those of the positive control pioglitazone. FC significantly lowered AI and CRI (p < 0.01) while it had no effect on adiponectin and leptin levels. Our results demonstrate that preventive treatment with FC significantly improved the lipid profile and decreased adipogenic risk factors in HFD rats most likely mediated through an increase in HDL‐C levels. Copyright © 2013 John Wiley & Sons, Ltd.     

Antiobesity Effects of Chinese Black Tea (Pu‐erh Tea) Extract and Gallic Acid

The antiobesity effects of Chinese black tea (Pu‐erh tea) and of gallic acid (GA) were investigated using in vitro and in vivo assays. Chinese black tea extract (BTE) and GA inhibited pancreatic lipase activity in a dose‐dependent manner in vitro; the IC(inhibitory concentration)₅₀ values were 101.6 and 9.2 µg/mL, respectively. Black tea extract (50, 100 mg/kg body weight (b.w.)) and GA (15, 45 mg/kg b.w.) significantly suppressed the elevation of blood triglyceride after oral administration of a corn oil emulsion (8 mL oil/kg b.w.) to male ddY mice. Moreover, the antiobesity effects of BTE and GA were also evaluated in a mouse model of diet‐induced obesity. Female ddY mice were divided into seven groups; normal diet (ND) group, high fat diet (HFD) group, BTE (0.2% and 0.6% of diets) groups, and GA (0.007%, 0.02% and 0.1% of diets) groups; the experimental groups were fed the test diets for 12 weeks. The BTE 0.6% and GA 0.1% groups showed significant suppression of weight gain. The weight of parametrial adipose tissue was strongly correlated with the body weight. These results suggest that GA contributes to the antiobesity effect of BTE as an active constituent by inhibiting pancreatic lipase activity. Copyright © 2011 John Wiley & Sons, Ltd.     

Fucoidan Prevents High‐Fat Diet‐Induced Obesity in Animals by Suppression of Fat Accumulation

This study examines the antiobesity effects of fucoidan in an animal model of diet‐induced obesity. Mice were fed a standard diet or high‐fat diet (HFD) for 5 weeks. After that, the mice were divided into four experimental groups, with 10 mice per group, including a standard diet group, HFD group, HFD containing 1% fucoidan (HFD + FUCO 1%) group and HFD containing 2% fucoidan (HFD + FUCO 2%) group. The fucoidan supplementation group had significantly decreased body‐weight gain, food efficiency ratio and relative liver and epididymal fat mass compared with the HFD group. The mice supplemented with fucoidan showed significantly reduced triglyceride, total cholesterol and low‐density lipoprotein levels in the plasma. Liver steatosis induced by the HFD improved in the fucoidan‐supplemented group. Furthermore, fucoidan affected the down‐regulation expression patterns of epididymal adipose tissue genes such as peroxisome proliferator‐activated receptor γ, adipose‐specific fatty acid binding protein and acetyl CoA carboxylase. Therefore, fucoidan may be considered for use in improving obesity. Copyright © 2013 John Wiley & Sons, Ltd.     

miR‐96 and autophagy are involved in the beneficial effect of grape seed proanthocyanidins against high‐fat‐diet‐induced dyslipidemia in mice

We aimed to investigate the possible signaling pathways underlying the regulation of grape seed proanthocyanidins extracts (GSPE) on lipid metabolism. One hundred male C57BL/6 mice were divided into four groups: control group (normal diet), GSPE group (normal diet + GSPE), high‐fat diet group (HFD), and high‐fat diet plus GSPE (200 mg/kg/day) group (HFD + GSPE). Mice received the diets for 180 days. Body weight and serum lipid levels were measured. Autophagic flux characteristics, such as accumulation of lipids, mitochondria, and autophagosomes in the liver, were detected using transmission electron microscopy. Expression profile of microRNAs (miRNAs) in the liver was determined using RNA microarray and quantitative real time polymerase chain reaction (qRt‐PCR). GSPE significantly decreased the weight gain, serum levels of triglycerides, total cholesterol, and low‐density lipoprotein cholesterol but increased high‐density lipoprotein cholesterol in the HFD mice. Autophagic flux was significantly increased by HFD but decreased by GSPE treatment. GSPE significantly attenuated HFD‐induced miR‐96 upregulation, which in turn reduced the expressions of miR‐96 downstream molecules, FOXO1, mTOR, p‐mTOR, and LC3A/B. These results suggested that the miR‐96 is involved in the protective effect of GSPE against HFD‐induced dyslipidemia. Possible mechanisms might be through mTOR and FOXO1, which facilitate autophagic flux for clearance of lipid accumulation.     

Synergistic effects of the capsaicinoid nonivamide and rosuvastatin on obesity‐related endothelial dysfunction in rat fed a high‐fat diet

Capsaicinoid nonivamide (PAVA) and rosuvastatin (RSV) have been shown to exert antioxidant and anti‐obesity effects in various animal models, but it is unknown whether their combination would be an effective treatment for obesity‐related endothelial dysfunction. This study aimed to investigate the mechanism of PAVA in synergy with RSV. Male Sprague–Dawley rats were given a high‐fat diet (HFD) or normal diet during a 20‐week period. At 16 weeks, rats in each diet group were divided into subgroups. Normal diet rats were divided into Normal diet control, Normal diet with PAVA, and Normal diet with RSV groups. HFD rats were subdivided into HFD control, HFD with PAVA, HFD with RSV, and HFD with PAVA + RSV groups and evaluated for metabolic parameters, blood pressure, aortic function, and histological change of the aorta in rats. Our results showed the combined therapy had a significantly greater effect than the monotherapy in all measured parameters; this was indicated by improvement in insulin sensitivity and aortic function, decreased blood pressure, lower oxidative stress, and prevention of vascular damage. The synergistic effect of the PAVA and RSV can protect HFD‐induced obesity‐related endothelial dysfunction, suggesting that the combination of PAVA and RSV could be an effective alternative treatment for obesity‐related complications in patients with cardiovascular disease.     

Effect of the Capsicoside G‐rich Fraction from Pepper (Capsicum annuum L.) Seeds on High‐fat Diet‐induced Obesity in Mice

Obesity is one of the most common metabolic syndromes and is a major threat to human health worldwide. Given the size of this problem, there is growing interest in natural agents that may decrease obesity. In this study, we investigated the anti‐obesity effect of a capsicoside G‐rich fraction (CRF; 13.35% capsicoside G) isolated from pepper seeds in diet‐induced obese mice. C57BL/6J mice were fed either a normal diet or a high‐fat diet (HFD), with or without CRF (HFD + CRF; 10 and 100 mg/kg body weight). The body weight and food efficiency ratio of mice fed HFD + CRF were lower in comparison to that of mice fed only an HFD. Epididymal adipose tissue weight and adipocyte hypertrophy were significantly lower in HFD + CRF mice than in HFD mice. The fat deposition in the liver of mice fed HFD + CRF was lower compared to that of mice fed only an HFD. CRF significantly reversed the HFD‐induced elevation of the expression of key adipocyte differentiation regulators, including peroxisome proliferator‐activated receptor γ, CCAAT/enhancer‐binding protein α, sterol regulatory element binding protein 1c, and their target genes. These results suggest that CRF could be used as dietary therapy for the prevention of obesity and obesity‐related metabolic diseases. Copyright © 2016 John Wiley & Sons, Ltd.     

The Anti‐Obesity Effects of the Dietary Combination of Fermented Red Ginseng with Levan in High Fat Diet Mouse Model

In this study, to evaluate the anti‐obesity effects of fermented red ginseng (FG), levan (L), and their combination (FGL), we investigated their effects on the weights of body, liver and white adipose tissue, lipid profiles, and biomarkers for insulin resistance in high fat diet (HFD)‐induced obese C57BL/6J male mice. Furthermore, the levels of leptin in the serum were measured. FG (150 mg/kg/d), L (100 mg/kg/d), and FGL (150 mg/kg/d of FG plus 100 mg/kg/d of L) were administered orally to mice daily for 11 weeks. After 11 weeks feeding, FGL showed significantly lower body weight and fat mass with decreasing food efficiency ratio than the HFD control mice. In addition, the FGL group was significantly lower in the levels of total cholesterol and fasting blood glucose and score of the homeostatic model assessment of insulin resistance. Furthermore, FGL decreased serum leptin levels compared to the HFD control group. Taken together, FGL showed a significant anti‐obesity effect in HFD‐induced obese mice and prevent insulin and leptin resistance. FGL may be potentially useful for the prevention of obesity. Copyright © 2013 John Wiley & Sons, Ltd.     

Hypolipidemic activity and mechanisms of the total phenylpropanoid glycosides from Ligustrum robustum (Roxb.) Blume by AMPK‐SREBP‐1c pathway in hamsters fed a high‐fat diet

The aim of this study was to evaluate the hypolipidemic effect and mechanisms of total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) in hamsters fed a high‐fat diet and to discover bioactive components in HepG2 cell model induced by oleic acid. LRTPG of high (1.2 g/kg), medium (0.6 g/kg), and low (0.3 g/kg) doses was administrated daily for 21 consecutive days in hamsters. We found that in hamsters fed a high‐fat diet, LRTPG effectively reduced the concentrations of plasma triglycerides (TG), free fatty acid, total cholesterol, low‐density lipoprotein cholesterol, and hepatic TG and total cholesterol. And the compounds acteoside, ligupurpuroside A, ligupurpuroside C, and ligupurpuroside D significantly inhibited lipid accumulation in HepG2 cell at the concentration of 50 μmol/L. Mechanism research demonstrated that LRTPG increased the levels of phospho–AMP‐activated protein kinase and phospho‐sterol regulatory element binding protein‐1c in liver, further to suppress the downstream lipogenic genes as stearoyl‐CoA desaturase 1, glycerol‐3‐phosphate acyltransferase, 1‐acylglycerol‐3‐phosphate O‐acyltransferase 2, and diacylglycerol acyltransferase 2. In addition, LRTPG increased the hydrolysis of circulating TG by up‐regulating lipoprotein lipase activities. These results indicate that LRTPG prevents hyperlipidemia via activation of hepatic AMP‐activated protein kinase‐sterol regulatory element binding protein‐1c pathway.     

Regulation of obesity and lipid disorders by extracts from Angelica acutiloba root in high-fat diet-induced obese rats

The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of Angelica acutiloba root (Japanese Dong Quai). High‐fat diet (HFD)‐induced obese rats were treated orally with the polyphenolic‐rich extract of Angelica acutiloba root (AARE) once daily for 8 weeks. The AARE (300 mg/kg per day) supplementation significantly lowered body weight gain, visceral fat‐pad weights and plasma lipid levels, as well as the coronary artery risk index and the atherogenic index of HFD‐fed rats. The AARE caused dose related reductions in the hepatic triglyceride and cholesterol contents, as well as lowered hepatic lipid droplet accumulation and epididymal adipocyte size in the HFD‐fed rats. The AARE reversed the HFD‐induced down‐regulation of the hepatic peroxisome proliferator activated receptor‐α (PPARα). The HFD‐induced decreases of the hepatic protein level of acyl‐CoA oxidase (ACO), and the cytochrome P450 isoform 4A1 (CYP4A1) was up‐regulated by AARE. The elevated expressions of hepatic sterol regulatory element binding proteins (SREBPs) of HFD‐fed rats were lowered by AARE. These results suggest that AARE attenuated visceral fat accumulation and improved hyperlipidemia in HFD‐induced obesity by increasing lipid metabolism through the down‐regulation of SREBPs and enhanced the expression of ACO and CYP4A1 in the liver, which was likely mediated by up‐regulation of the expression of hepatic PPARα. Copyright © 2011 John Wiley & Sons, Ltd.     

Effects of Ilex latifolia and Camellia sinensis on Cholesterol and Circulating Immune Complexes in Rats Fed with a High‐Cholesterol Diet

Hypercholesterolaemia is one of the risk factors for atherosclerosis and subsequent cardiovascular disease. Here, we investigated the effects of dietary supplementation with Ilex latifolia or green tea (Camellia sinensis) on the levels of plasma total cholesterol, high‐density lipoprotein cholesterol and circulating immune complexes in Sprague Dawley rats fed with a high‐cholesterol diet. We demonstrated that daily administration by gavage of I. latifolia or C. sinensis at doses of 1.0 or 2.0 g/kg body weight for 30 days resulted in a significant decrease in plasma total cholesterol levels and circulating immune complexes and an increase in high‐density lipoprotein cholesterol in rats fed with a high‐cholesterol diet compared with levels in the high‐cholesterol diet control group. C. sinensis was more effective than I. latifolia. I. latifolia and C. sinensis could be used as food supplements to protect against the development of hypercholesterolaemia. Copyright © 2012 John Wiley & Sons, Ltd.     

Chlorogenic Acid Exhibits Cholesterol Lowering and Fatty Liver Attenuating Properties by Up‐regulating the Gene Expression of PPAR‐α in Hypercholesterolemic Rats Induced with a High‐Cholesterol Diet

Hypercholesterolemia is a major risk factor for the development of cardiovascular disease and nonalcoholic fatty liver disease. Natural compounds have been proved to be useful in lowering serum cholesterol to slow down the progression of cardiovascular disease and nonalcoholic fatty liver disease. In the present study, the hypocholesterolemic and hepatoprotective effects of the dietary consumption of chlorogenic acid were investigated by monitoring plasma lipid profile (total cholesterol, triglycerides, high‐density lipoprotein and low‐density lipoprotein) in Sprague–Dawley rats fed with a normal diet, a high‐cholesterol diet or a high‐cholesterol diet supplemented with chlorogenic acid (1 or 10 mg/kg/day p.o.) for 28 days. Chlorogenic acid markedly altered the increased plasma total cholesterol and low‐density lipoprotein but decreased high‐density lipoprotein induced by a hypercholesterolemic diet with a dose‐dependent improvement on both atherogenic index and cardiac risk factor. Lipid depositions in liver were attenuated significantly in hypercholesterolemic animals supplemented with chlorogenic acid. It is postulated that hypocholesterolemic effect is the primary beneficial effect given by chlorogenic acid, which leads to other secondary beneficial effects such as atheroscleroprotective, cardioprotective and hepatoprotective functions. The hypocholesterolemic functions of chlorogenic acid are probably due to the increase in fatty acids unitization in liver via the up‐regulation of peroxisome proliferation‐activated receptor α mRNA. Copyright © 2012 John Wiley & Sons, Ltd.     

A combination of grape extract, green tea extract and L-carnitine improves high-fat diet-induced obesity, hyperlipidemia and non-alcoholic fatty liver disease in mice

To develop a therapeutic agent for obesity-related metabolic disorders, a mixture of dietary components was prepared, including grape extract, green tea extract and l-carnitine (RGTC), and its effects on obesity, hyperlipidemia and non-alcoholic fatty liver disease examined. The RGTC dramatically inhibited the high-fat diet (HFD)-induced increase in body weight and fat in C57BL/6 mice, whereas food consumption was not affected by RGTC treatment. The RGTC also concentration-dependently suppressed the HFD-induced increase in plasma lipids, such as low-density lipoprotein cholesterol and triglycerides. In addition, increases in liver weight and liver steatosis were returned to normal by RGTC treatment in HFD-fed C57BL/6 mice. The plasma levels of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were also significantly down-regulated by RGTC treatment. These results suggest that RGTC suppressed HFD-induced obesity, hyperlipidemia and non-alcoholic fatty liver disease, suggesting that RGTC supplementation might be a promising adjuvant therapy for the treatment of these metabolic disorders.     

Aurantio‐obtusin improves obesity and insulin resistance induced by high‐fat diet in obese mice

Aurantio‐obtusin (AUR) is the main bioactive compound among the anthraquinones, from Cassia seed extract. This study was conducted to identify whether AUR could improve obesity and insulin resistance, induced by a high‐fat diet in obese mice. Mice were fed a high‐fat diet for 6 weeks and were then assigned to the high‐fat diet (HFD) control group, the AUR 5 mg/kg group, or the AUR 10 mg/kg group. AUR improves glucose by activating the expression of PI3K, Akt and GLUT4, GLUT2. AUR altered the expression levels of several lipid metabolism‐related and adipokine genes. AUR decreased the mRNA expression of PPAR‐γ, FAS and increased the mRNA expression of PPAR‐α in liver. AUR lowered SREBP‐1c, FAS, SCD‐1, inflammatory cytokines, and increased the expression of PPAR‐γ, PPAR‐α, CPT‐1, and adiponectin in white adipose tissue (WAT). AUR docking with the insulin receptor showed that the residues of the insulin receptor, ectodomain, were the same as those around the emodin. The effect of AUR may be elicited by regulating the activity of the insulin signaling pathway, expression of lipid metabolism‐related genes, and expression of inflammatory cytokine markers to improve adiposity, insulin resistance, and dyslipidemia.     

Black tea prevents high fat diet-induced non-alcoholic steatohepatitis

The chemoprotective actions of aqueous black tea extract (BTE) against high-fat diet (HFD) (60%)-induced non-alcoholic steatohepatitis (NASH) were examined in Wistar rats of both sexes. The results indicated that the HFD rats had higher concentrations of serum glucose, cholesterol, triglycerides, low-density lipoprotein, very low-density lipoprotein, high-density lipoprotein and bilirubin than the corresponding control rats. The enzymes serum aspartate aminotransferase and alanine aminotransferase, which are indicators of liver function, also exhibited higher levels of activity in HFD rats. BTE extract supplementation was found to correct such steatohepatitis-linked biochemical changes. HFD-induced steatohepatitis was associated with substantial pro-oxidant conditions in rat liver, as evidenced by the higher content of malondialdehyde, nitric oxide production and glutathione depletion, with a concomitant decrease in liver antioxidant status caused by reducing superoxide dismutase and catalase activity. In addition, rats with steatohepatitis showed a significantly higher expression of inducible nitric oxide synthase, caspase-3 activity and DNA fragmentation. BTE reversed the changes in the pro-oxidant and antioxidant status of the liver, and protected against apoptotic, cytogenetic and hepatocellular damage. In summary, these data suggest that nutritional support with antioxidants may be useful in preventing oxidative damage and the progression of NASH.     

Prenylated flavonoid‐standardized extract from seeds of Psoralea corylifolia L. activated fat browning in high‐fat diet–induced obese mice

We investigated the effects of the prenylated flavonoid‐standardized extract (PFE) from the seeds of Psoralea corylifolia L. on countering obesity, which increases energy expenditure and stimulates thermogenesis in subcutaneous white adipose tissue (sWAT) and brown adipose tissue (BAT). For 12 weeks, C57BL/6 mice were fed a controlled high‐fat diet (HFD) or HFDs with 0.2% or 0.5% w/w PFE. In vitro, the differentiation of 3 T3‐L1 cells was used to elicit thermogenesis in the presence of PFE. PFE obviously reduced body weight and fat mass in a dose‐dependent manner, increased energy expenditure, improved insulin sensitivity, and prevented hepatic steatosis by increasing lipid oxidation and secretion in HFD‐fed mice. Moreover, PFE induced clear browning in sWAT, significantly increased phosphorylation of AMPKα1/2 and p38, increased BAT activity and the differentiation of 3 T3‐L1 by increasing the expression of uncoupling protein 1 and other thermogenic genes. Our study showed that PFE prevented obesity by increasing browning and activating thermogenic genes in sWAT and BAT, improving glucose homeostasis, and protecting hepatic steatosis.     

Hypercholesterolemia and Ecto‐enzymes of Purinergic System: Effects of Paullinia cupana

Hypercholesterolemia is a metabolic disorder characterized by high levels of low‐density lipoprotein and blood cholesterol, causing inflammatory lesion. Purinergic signaling modulates the inflammatory and immune responses through adenine nucleotides and nucleoside. Guaraná has hypocholesterolemic and antiinflammatory properties. Considering that there are few studies demonstrating the effects of guaraná powder on the metabolism of adenine nucleotides, we investigated its effects on the activity of ecto‐nucleoside triphosphate diphosphohydrolase (E‐NTPDase) and ecto‐adenosine deaminase activity in lymphocytes of rats with diet‐induced hypercholesterolemia. The rats were divided into hypercholesterolemic and normal diet groups. Each group was subdivided by treatment: saline, guaraná powder 12.5, 25, or 50 mg/kg/day and caffeine concentration equivalent to highest dose of guaraná, fed orally for 30 days. An increase in adenosine triphosphate hydrolysis was observed in the lymphocytes of rats with hypercholesterolemia and treated with 25 or 50 mg/kg/day when compared with the other groups. The hypercholesterolemic group treated with the highest concentration of guaraná powder showed decreased ecto‐adenosine deaminase activity compared with the normal diet groups. Guaraná was able to reduce the total cholesterol and low‐density lipoprotein cholesterol to basal levels in hypercholesterolemic rats. High concentrations of guaraná associated with a hypercholesterolemic diet are likely to have contributed to the reduction of the inflammatory process. Copyright © 2015 John Wiley & Sons, Ltd.