Whole berries versus berry anthocyanins: interactions with dietary fat levels in the C57BL/6J mouse model of obesity

Male C57BL/6J mice received diets with either 10% of calories from fat (LF) or a high-fat diet [45% (HF45) or 60% (HF60) calories from fat] for 92 days (expt 1) or 70 days (expt 2). These were given with or without freeze-dried powders from whole blueberries (BB) or strawberries (SB) (expt 1) or purified anthocyanin extracts from BB or SB (expt 2). Body composition was determined utilizing Echo MRI. Berries added to the LF diet did not alter weight gain, final body weights, body fat, or protein (percent body weight) or diet (grams) or energy (kilocalories) intake. However, in both HF45- and HF60-fed mice, weight gain, final weights, body fat (percent), and epididymal fat weights increased and body protein decreased ( p < 0.01) compared to LF mice. In mice fed HF45 diet plus BB, body weight gains, body fat (percent of BW), and epididymal fat weights were significantly greater than those in the HF45-fed controls, whereas weights of mice fed SB HF were similar to those of HF controls. SB or BB feeding did not alter glucose tolerance, although glucose tolerance decreased with age and in HF45 versus LF mice. Baseline plasma glucose was lower in SB- versus HF45-fed mice. After 8 weeks, mice fed the HF60 diet plus purified anthocyanins from BB in the drinking water had lower body weight gains and body fat than the HF60-fed controls. Anthocyanins fed as the whole blueberry did not prevent and may have actually increased obesity. However, feeding purified anthocyanins from blueberries or strawberries reduced obesity.     

Muscadine Grape ( Vitis rotundifolia ) and Wine Phytochemicals Prevented Obesity-Associated Metabolic Complications in C57BL/6J Mice

The objective of this study was to determine the effects of muscadine grape or wine (cv. Noble) phytochemicals on obesity and associated metabolic complications. Muscadine grape or wine phytochemicals were extracted using Amberlite FPX66 resin. Male C57BL/6J mice were given a low-fat diet (LF, 10% kcal fat), high-fat diet (HF, 60% kcal fat), HF + 0.4% muscadine grape phytochemicals (HF+MGP), or HF + 0.4% muscadine wine phytochemicals (HF+MWP) for 15 weeks. At 7 weeks, mice fed HF+MGP had significantly decreased body weights by 12% compared to HF controls. Dietary MGP or MWP supplementation reduced plasma content of free fatty acids, triglycerides, and cholesterol in obese mice. Inflammation was alleviated, and activity of glutathione peroxidase was enhanced. Consumption of MGP or MWP improved insulin sensitivity and glucose control in mice. Thus, consumption of muscadine grape and wine phytochemicals in the diet may help to prevent obesity-related metabolic complications.     

Amelioration of obesity and glucose intolerance in high-fat-fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas)

Much attention has been focused on food that may be beneficial in preventing diet-induced body fat accumulation and possibly reduce the risk of diabetes and heart disease. Cornelian cherries (Cornus mas) are used in the preparation of beverages in Europe and also to treat diabetes-related disorders in Asia. In this study, the most abundant bioactive compounds in C. mas fruits, the anthocyanins and ursolic acid, were purified, and their ability to ameliorate obesity and insulin resistance in C57BL/6 mice fed a high-fat diet was evaluated. Mice were initially fed a high-fat diet for 4 weeks and then switched to a high-fat diet containing anthocyanins (1 g/kg of high-fat diet) and ursolic acid (500 mg/kg of high-fat diet) for an additional 8 weeks. The high-fat diet induced glucose intolerance, and this was prevented by anthocyanins and ursolic acid. The anthocyanin-treated mice showed a 24% decrease in weight gain. These mice also showed decreased lipid accumulation in the liver, including a significant decrease in liver triacylglycerol concentration. Anthocyanin and ursolic acid treated mice exhibited extremely elevated insulin levels. Both treatments, however, showed preserved islet architecture and insulin staining. Overall, these data suggest that anthocyanins and ursolic acid purified from C. mas fruits have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity.     

Effect of a proanthocyanidin-rich extract from longan flower on markers of metabolic syndrome in fructose-fed rats

Recent evidence strongly suggests that oxidative stress due to redox imbalance is highly associated with metabolic syndrome. The objective of this study was to evaluate the effect of the supplementation of longan flower water extract (LFWE), which showed powerful antioxidative activity in vitro, on markers of metabolic syndrome in a fructose-fed rat model. Male Sprague-Dawley rats were randomly divided into four groups: group C, fed with standard Purina chow; group F, fed with high-fructose diet (HF) alone; group L, fed with HF plus LFWE 125 mg/kg bw per day by gavage; and group H, fed HF plus LFWE 250 mg/kg bw per day by gavage. The dietary manipulation lasted for 14 weeks. Results of our study showed that rats fed with HF resulted in oxidative stress and affected the antioxidant status including plasma thiobarbituric acid and liver antioxidant enzyme activity. Treatment with LFWE significantly augmented the antioxidant system. HF was able to cause insulin resistance and elevation of the blood pressure. The supplementation of LFWE ameliorated insulin resistance by enhancing the expression of insulin signaling pathway related proteins, including insulin receptor substrate-1 and glucose transporter 4. LFWE supplementation was also found to decrease systolic blood pressure. These findings indicate that longan flower water extract may improve the symptoms of metabolic syndrome in fructose-fed rats.     

Lower weight gain and hepatic lipid content in hamsters fed high fat diets supplemented with white rice protein, brown rice protein, soy protein, and their hydrolysates

The physiological effects of the hydrolysates of white rice protein (WRP), brown rice protein (BRP), and soy protein (SP) hydrolyzed by the food grade enzyme, alcalase2.4 L, were compared to the original protein source. Male Syrian Golden hamsters were fed high-fat diets containing either 20% casein (control) or 20% extracted proteins or their hydrolysates as the protein source for 3 weeks. The brown rice protein hydrolysate (BRPH) diet group reduced weight gain 76% compared with the control. Animals fed the BRPH supplemented diet also had lower final body weight, liver weight, very low density lipoprotein cholesterol (VLDL-C), and liver cholesterol, and higher fecal fat and bile acid excretion than the control. Expression levels of hepatic genes for lipid oxidation, PPARα, ACOX1, and CPT1, were highest for hamsters fed the BRPH supplemented diet. Expression of CYP7A1, the gene regulating bile acid synthesis, was higher in all test groups. Expression of CYP51, a gene coding for an enzyme involved in cholesterol synthesis, was highest in the BRPH diet group. The results suggest that BRPH includes unique peptides that reduce weight gain and hepatic cholesterol synthesis.     

Effect of chitosan, O-carboxymethyl chitosan, and N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl] chitosan chloride on overweight and insulin resistance in a murine diet-induced obesity

Two water-soluble chitosan derivatives, O-carboxymethyl chitosan (O-CM-chitosan) and N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl] chitosan chloride (N-CQ-chitosan), were prepared, and the therapeutic effects of chitosan, O-CM-chitosan, and N-CQ-chitosan on insulin resistance were simultaneously evaluated by rats fed on a high-fat diet. The parameters of high-fat diet-induced rats indicated that chitosan and its two derivatives not only have low cytotoxicity but can control overnutrition by fat and achieve insulin resistance therapy. However, the results in experiment in vivo showed that the therapeutic degree varied by the molecular weight and surface charge of chitosan, O-CM-chitosan, and N-CQ-chitosan. N-CQ-chitosan with a MW of 5 × 10(4) decreased body weight, the ratio of fat to body weight, triglyceride, fasting plasma glucose, fasting plasma insulin, free fatty acid, and leptin by 11, 17, 44, 46, 44, 87, and 64% and increased fecal lipid by 95%, respectively.     

Antihyperlipidemic and body fat-lowering effects of silk proteins with different fibroin/sericin compositions in mice fed with high fat diet

The effect of silk protein with different fibroin/sericin compositions on body weight and lipid metabolism in high fat-fed mice was investigated. The animals were given experimental diets for 6 weeks: normal control (NC), high fat (HF) and high fat diet supplemented with F100 (pure fibroin, HF-F100), F81 (81:19 fibroin/sericin, w/w, HF-F81) or F50 (50:50 fibroin/sericin, w/w, HF-F50). The silk protein-fed mice showed markedly reduced body weight and enhanced lipid profile relative to the HF group. In general, the amount of body fat, triglyceride and total plasma cholesterol levels, atherogenic index and free fatty acid level tended to decrease, while the HDL-cholesterol level increased, with increased amount of sericin in the diet. This hypolipidemic effect was partly due to increased fecal lipid excretion, inhibition of lipogenesis and regulation of adipokine production. These findings illustrate that silk protein, particularly sericin, may be beneficial in the prevention of high fat diet-induced hyperlipidemia and obesity.     

High-fat diet enhances the accumulation of hexachlorobenzene (HCB) by pregnant rats during continuous exposure to HCB

To investigate the influence of a high-fat diet on HCB distribution and accumulation, pregnant rats in study 1 were fed a high-fat or control diet containing HCB, and, in study 2, pregnant rats were given a single HCB dose by intragastric gavage and HCB-free high-fat or control diet. In study 1, the high-fat diet group had higher HCB concentrations in fat tissues and liver than did the controls. In study 2, although the total amounts of HCB in the fat tissue and liver were greater in the high-fat diet group than in the controls, no significant differences in HCB concentration were observed between the two groups. The high-fat diet group also showed more fecal excretion of HCB. Therefore, HCB accumulation in rats fed a high-fat diet was enhanced more by continuous exposure to HCB than by administration of a single dose.     

Inhibition of tumorigenesis in ApcMin/+ mice by a combination of (-)-epigallocatechin-3-gallate and fish oil

The effect of a combination of (-)-epigallocatechin-3-gallate (EGCG) with fish oil on intestinal tumorigenesis in Apc (Min/+) mice fed a high-fat diet was investigated in the present study. The combined treatment of EGCG and fish oil for 9 weeks reduced the tumor number by 53% as compared to controls while neither agent alone had a significant effect. Apoptosis was significantly increased in all treatment groups. beta-Catenin nuclear positivity in adenomas from the combination group was lower than control mice, implicating the modulation of Wnt signaling by the combination. Fish oil and the combination significantly reduced prostaglandin E 2 (PGE 2) levels in small intestinal tumors as compared to controls, suggesting modulation of aberrant arachidonic acid metabolism by fish oil. Akt phosphorylation in adenomas was significantly reduced in all treatment groups, which may have contributed to the observed increase in apoptosis. The results indicate that a combination of low doses of EGCG and fish oil can inhibit tumor multiplicity in Apc (Min/+) mice.     

Dietary combination of conjugated linoleic acid (CLA) and pine nut oil prevents CLA-induced fatty liver in mice

Conjugated linoleic acid (CLA) strongly prevents fat accumulation in adipose tissue of mice, even if hepatic fat deposition and insulin resistance are concomitantly observed. This study investigated the possibility of maintaining the antiadiposity properties of CLA while preventing adverse effects such as liver steatosis and hyperinsulinemia. To this end, mice were divided into three groups and fed a standard diet (control) or a diet supplemented with 1% CLA (CLA) or a mixture of 1% CLA plus 7.5% pine nut oil (CLA + P). The combination of CLA + P preserved the CLA-mediated antiadiposity properties (70% fat reduction), preventing hepatic steatosis and a sharp increase in plasmatic insulin starting from the eighth week of CLA treatment. The assay of both fatty acid synthesis and oxidation in the CLA + P mice revealed a time-dependent biphasic behavior of the corresponding enzymatic activities. A sudden change in these metabolic events was indeed found at the eighth week. A strong correlation between the changes in key enzymes of lipid metabolism and in insulin levels apparently exists in CLA-fed mice. Furthermore, lower levels of lipids, in comparison to values found in CLA-fed mice, were observed in the liver and plasma of CLA + P-fed animals.     

A black soybean seed coat extract prevents obesity and glucose intolerance by up-regulating uncoupling proteins and down-regulating inflammatory cytokines in high-fat diet-fed mice

Black soybean seed coat extract (BE) is a polyphenol-rich food material consisting of 9.2% cyanidin 3-glucoside, 6.2% catechins, 39.8% procyanidins, and others. This study demonstrated that BE ameliorated obesity and glucose intolerance by up-regulating uncoupling proteins (UCPs) and down-regulating inflammatory cytokines in C57BL/6 mice fed a control or high-fat diet containing BE for 14 weeks. BE suppressed fat accumulation in mesenteric adipose tissue, reduced the plasma glucose level, and enhanced insulin sensitivity in the high-fat diet-fed mice. The gene and protein expression levels of UCP-1 in brown adipose tissue and UCP-2 in white adipose tissue were up-regulated by BE. Moreover, the gene expression levels of major inflammatory cytokines, tumor necrosis factor-α and monocyte chemoattractant protein-1 were remarkably decreased by BE in white adipose tissue. BE is a beneficial food material for the prevention of obesity and diabetes by enhancing energy expenditure and suppressing inflammation.     

Preventive effects of taurine on development of hepatic steatosis induced by a high-fat/cholesterol dietary habit

Nonalcoholic fatty liver (NAFL) is also called hepatic steatosis and has become an emergent liver disease in developed and developing nations. This study was to exam the preventive effects of taurine (Tau) on the development of hepatic steatosis via a hamster model. Although hepatic steatosis of hamsters was induced by feeding a high-fat/cholesterol diet, drinking water containing 0.35 and 0.7% Tau improved (p < 0.05) the serum lipid profile. Meanwhile, the smaller (p < 0.05) liver sizes and lower (p < 0.05) hepatic lipids in high-fat/cholesterol dietary hamsters drinking Tau may be partially due to higher (p < 0.05) fecal cholesterol, triacylglycerol, and bile acid outputs. In the regulation of lipid homeostasis, drinking a Tau solution upregulated (p < 0.05) low-density lipoprotein receptor and CYP7A1 gene expressions in high-fat/cholesterol dietary hamsters, which result in increased fecal cholesterol and bile acid outputs. Drinking a Tau solution also upregulated (p < 0.05) peroxisome proliferator-activated receptor-α (PPAR-α) and uncoupling protein 2 (UPC2) gene expressions in high-fat/cholesterol dietary hamsters, thus increasing energy expenditure. Besides, Tau also enhanced (p < 0.05) liver antioxidant capacities (GSH, TEAC, SOD, and CAT) and decreased (p < 0.05) lipid peroxidation (MDA), which alleviated liver damage in the high-fat/cholesterol dietary hamsters. Therefore, Tau shows preventive effects on the development of hepatic steatosis induced by a high-fat/cholesterol dietary habit.     

Mulberry water extracts possess an anti-obesity effect and ability to inhibit hepatic lipogenesis and promote lipolysis

Obesity plays a critical role in dyslipidemia and related disorders. Mulberry water extracts (MWEs) contain polyphenols, including gallic acid, chlorogenic acid, rutin, and anthocyanins. In this study, using 6-week-old male hamsters, we investigated the anti-obese effect of MWEs. After 12 weeks of treatment, MWEs lowered high-fat diet (HFD)-induced body weight and visceral fat, accompanied with hypolipidemic effects by reducing serum triacylglycerol, cholesterol, free fatty acid, and the low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio (n=8 for each group). MWEs decreased hepatic lipids, thus protected livers from impairment. The hepatic peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1 were elevated, while fatty acid synthase and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase were reduced by MWEs, indicating that MWEs regulated lipogenesis and lipolysis, which exerted the anti-obese and hypolipidemic effects. Noticeably, MWEs showed both efficacy and safety in vivo. In concluson, MWEs can be used to reduce body weight, serum, and liver lipids.     

High-Fat diet enhances accumulation of hexachlorobenzene in rat dams and delays its transfer from rat dams to suckling pups through milk

Effect of diets on the distribution and transfer of hexachlorobenzene (HCB) from dams to fetuses and suckling pups was investigated. In pregnant rats, the amount of HCB accumulated in fat tissues of the high-fat diet group was higher than that of the control diet group (P < 0.05). The amounts of HCB in fetuses of the high-fat and control diet groups were estimated to be about 0.28 and 0.12% of the dam's total intake during pregnancy, respectively. In both groups, a large proportion of HCB in dams disappeared during lactation period and was transferred to their pups through the milk. In the pups of the high-fat diet group, the amount of HCB in stomach contents was lower immediately after birth and decreased slowly compared with that in the control diet group during lactation. These results showed that a high-fat diet reduced the speed of the transfer of HCB from the dams to their suckling pups through milk.     

Effects of konjac glucomannan on putative risk factors for colon carcinogenesis in rats fed a high-fat diet

The aim of this study was to determine effects of konjac glucomannan (KGM) in a high fat corn oil diet on risk factors of colon carcinogenesis, that is, fecal β-glucuronidase, mucinase, and bile acids, and on preventive factors, that is, fecal microflora and cecal short-chain fatty acids (SCFAs). Sprague-Dawley rats (n = 8 animals per group) were fed a normal-fat fiber-free (5% corn oil, w/w) or high-fat (25% corn oil, w/w) diet containing no fiber, KGM (5%, w/w), or inulin (5%, w/w, as a prebiotic control) for 4 weeks. Results indicated that the high-fat fiber-free diet significantly elevated the fecal β-glucuronidase and mucinase activities and total bile acid concentration and decreased cecal SCFA contents, as compared with its normal-fat counterpart. The incorporation of KGM, as well as inulin, into the high-fat fiber-free diet beneficially reduced the fecal β-glucuronidase and mucinase activities and lithocholic acid (secondary bile acid) concentration. Although KGM elevated the daily fecal total bile acid excretion, the change was due to the primary, instead of the secondary, bile acids. In addition, KGM beneficially promoted the daily fecal excretion of bifidobacteria and lactobacilli and cecal SCFA contents, as compared with the high-fat fiber-free diet. Therefore, the present study suggests that KGM potentially attenuated the high fat-induced risk in colon carcinogenesis.     

Improvement of obesity phenotype by Chinese sweet leaf tea (Rubus suavissimus) components in high-fat diet-induced obese rats

Drinking an herbal tea to lose weight is a well-liked concept. This study was designed to examine the possible improvement of obesity phenotype by a new tea represented by its purified components, gallic acid, ellagic acid, and rubusoside (GER). Male obese-prone SD rats were given low-fat diet, high-fat diet, or high-fat diet plus GER at the dose of 0.22 g/kg of body weight for 9 weeks. GER significantly reduced body weight gain by 22% compared to the high-fat diet control group with 48% less abdominal fat gain. Food intake was not affected. Blood glucose was lowered in the GER-treated group, whereas serum triglycerides and cholesterol were significantly reduced by 50%. This improved obesity phenotype may be associated with the attenuated expression of vascular endothelial growth factor in preadipocyte 3T3-L1 cells. Although other underlying, possibly multiple, mechanisms behind the improved phenotype are largely unknown, the observed improvement of multiple obesity-related parameters by the new tea warrants further investigations.     

Konjac glucomannan and inulin systematically modulate antioxidant defense in rats fed a high-fat fiber-free diet

The aim of this study was to investigate the effects of konjac glucomannan (KGM) and inulin on the balance between pro-oxidative status and antioxidative defense systems in the colon, liver, and plasma of rats fed a high-fat fiber-free diet. Male Sprague-Dawley rats (n = 8 animals per group) were fed a high-fat (25% corn oil, w/w) fiber-free diet or that supplemented with KGM or inulin fiber (5%, w/w) for 4 weeks. The index of pro-oxidative status, malondialdehyde (MDA), and blood lymphocyte DNA damage; the antioxidative defense, that is, antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase) in the colonic mucosa and liver; and the plasma antioxidant levels were determined. The fermentation of fiber was shown in fecal short-chain fatty acids. Incorporation of KGM and inulin into the high-fat fiber-free diet beneficially reduced the MDA levels of the colon and liver and DNA damage in blood lymphocytes. On the other hand, both fibers enhanced the antioxidative defense systems by up-regulating the gene expressions of glutathione peroxidase and catalase in the colonic mucosa and of superoxide dismutase and catalase in the liver. Furthermore, KGM and inulin promoted antioxidative status in the blood by elevating the α-tocopherol level. KGM and inulin were well-fermented in rats and increased the concentration and daily excretion of fecal short-chain fatty acids, especially acetate and butyrate. These results suggest that in vivo utilization of KGM and inulin stimulated both local and systemic antioxidative defense systems in rats.     

Hypolipidemic and Body Fat–Lowering Effects of Giant Embryo Brown Rice (Seonong 17 and Keunnunjami) in High‐Fat‐Fed Mice

The effects of giant embryo brown rice Seonong 17 and Keunnunjami, in comparison with that of ordinary normal brown rice, on the body weight and lipid profile in mice under a high‐fat diet condition were investigated. The animals were fed with experimental diets for eight weeks: normal control, high fat (HF), and high fat supplemented with normal brown rice, Seonong 17 rice, or Keunnunjami rice powder. Their body and fat weights, lipid profiles, lipogenic enzyme activities, and adipokine concentrations were determined. Significant differences between the animal groups were analyzed with Tukey's test (P < 0.05). A marked increase in the body weight and fat, plasma triglyceride and total cholesterol concentrations, and free fatty acid level were found in HF mice relative to the control group. On the other hand, diet supplementation with rice, particularly the giant embryo rice samples, significantly suppressed this high‐fat‐induced body weight gain and hyperlipidemia via regulation of lipogenesis and adipokine production. Both the Seonong 17 and Keunnunjami exhibited greater hypolipidemic and body fat–lowering effects than the normal brown rice. The results demonstrate that these giant embryo mutants may be beneficial as biomaterials for functional foods with antiobesity and hypolipidemic effects.     

Weight gain reduction in mice fed Panax ginseng saponin, a pancreatic lipase inhibitor

Roots of the herb Panax ginseng are known to contain high levels of bioactive saponins. Here, we isolated saponins from ginseng root powder and studied their inhibitory effect on the absorption of dietary fat in male Balb/c mice. Consumption of ginseng saponins suppressed the expected increase in body weight and plasma triacylglycerols, following a high-fat diet and observed higher intake. Consumption of ginseng saponins had no effect on the concentration of the total plasma cholesterol in both chow and high-fat diets in mice. The mode by which saponins from ginseng inhibit lipid metabolism was assessed as the in vitro inhibition of pancreatic lipase. Ginseng saponin inhibited pancreatic lipase with an apparent IC50 value of 500 mug/mL. Our results suggest that the anti-obesity and hypolipidemic effects of Ginseng in high-fat diet-treated mice were attributed to the isolated saponin fraction. These metabolic effects of the ginseng saponins may be mediated by inhibition of pancreatic lipase activity.     

Impact of high-fat and high-carbohydrate diets on liver metabolism studied in a rat model with a systems biology approach

The aim of the present study was to investigate the use of an integrated metabolomics and proteomics approach in the elucidation of diet-induced effects on hepatic metabolism in a rat model. Nuclear magnetic resonance (NMR)-based metabolomics of liver extracts revealed a pronounced effect of a high-fat diet on the hepatic betaine content, whereas a carbohydrate-rich diet induced increases in hepatic glucose. In addition, the metabolomic investigations revealed that the high-fat diet was associated with increased hepatic lipid levels, which was not evident with the carbohydrate-rich diet. The proteomic investigations revealed strong high-fat diet effects on the expression of 186 proteins in the liver including malate dehydrogenase. Comparison of malate dehydrogenase expression determined by proteomics and NMR metabolite profiles revealed correlations between malate dehydrogenase and lactate, glucose, and glutamine/glutamate signals, thereby demonstrating a diet-induced regulation that was evident at both proteomic and metabolomic levels.