Bungo Shirouchi

Effects of three different highly purified n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/KsJ-db/db mice.

Triglycerides (TG) consisting of highly purified (>97%) n-3 series highly unsaturated fatty acids, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), were administered to C57BL/KsJ-db/db mice for 4 weeks by pair-feeding to compare their effects on lipid metabolism and to evaluate the effects of DPA on lipid metabolism. The hepatic TG level and total amount was decreased by treatment with DHA and DPA compared to the control. The efficacy of DPA was greater than that of EPA, but less than that of DHA. In contrast, EPA had the greatest serum TG reducing effect. The hepatic cytosol fraction of the DHA-treated group contained the lowest fatty acid synthase (FAS) and malic enzyme (ME) activity levels. Furthermore, the DHA-treated group contained the highest serum adiponectin concentrations. These findings indicate that the strong hepatic TG-lowering effect of DHA is due to the suppression of TG synthesis. The same tendencies were observed in DPA-treated mice, and the effect was stronger than that observed in EPA-treated mice, but equivalent to that observed in DHA-treated mice. Based on these results, DPA possesses lipid metabolism-improving effects. The beneficial effects of DPA for lipid metabolism were not superior to those of EPA and DHA, and the effect was always intermediate between those of EPA and DHA.

Dietary phosphatidylinositol prevents the development of nonalcoholic fatty liver disease in Zucker (fa/fa) rats.

Recent studies have shown that dietary phospholipids, especially phosphatidylcholine and phosphatidylserine, have various beneficial biological effects. However, there are not enough data concerning the physiological function of dietary phosphatidylinositol (PI). The metabolic syndrome, a cluster of metabolic abnormalities such as dyslipidemia, diabetes mellitus, and hypertension, is a widespread and increasingly prevalent disease in industrialized countries. Nonalcoholic fatty liver disease (NAFLD) is often associated with features of the metabolic syndrome. NAFLD describes the spectrum of liver damage ranging from hepatic steatosis to steatohepatitis, liver fibrosis, and cirrhosis, and it is emerging as the most common liver disease worldwide. The present study examined whether dietary PI protects Zucker ( fa/ fa) rats from the metabolic syndrome. For 4 weeks, rats were fed semisynthetic diets containing either 7% soybean oil or 5% soybean oil plus 2% PI. Dietary PI markedly prevented the development of hepatomegaly and hepatic steatosis and lowered hepatic injury markers in serum. Additionally, hyperinsulinemia was relieved by the feeding of dietary PI in Zucker rats. These effects were attributable to an increase in serum adiponectin, enhancement of fatty acid beta-oxidation, and suppression of mRNA expression of inflammatory genes in the liver. This is the first report that dietary PI increases serum adiponectin level and prevents the development of NAFLD in a rat model of the metabolic syndrome.

Effects of citrus auraptene (7-Geranyloxycoumarin) on hepatic lipid metabolism in vitro and in vivo

Recent reports have shown that citrus auraptene (7-geranyloxycoumarin) possesses valuable pharmacological properties, including anticarcinogenic, anti-inflammatory, antihelicobacter, antigenotoxic, and neuroprotective effects. In the present study, we investigated the effect of dietary auraptene on hepatic lipid metabolism both in vitro and in vivo. Results suggested that auraptene has the ability to normalize lipid abnormalities in HepG2 hepatocytes. After 4 weeks of auraptene feeding, abdominal white adipose tissue weight and hepatic triglyceride (TG) levels were dose-dependently lowered in Otsuka Long-Evans Tokushima fatty (OLETF) rats. The activities of carnitine palmitoyltransferase, a key enzyme in mitochondrial fatty acid β-oxidation, and peroxisomal β-oxidation were markedly and dose-dependently enhanced in OLETF rat livers by auraptene feeding. Additionally, hepatic expression of acyl-CoA oxidase, the initial enzyme of the peroxisomal β-oxidation system, was significantly and dose-dependently enhanced by auraptene administration. These results suggest that auraptene administration alleviates obesity and hepatic TG accumulation in part through lipolysis enhancement in the livers of obese OLETF rats.

Lactobacillus gasseri SBT2055 reduces postprandial and fasting serum non-esterified fatty acid levels in Japanese hypertriacylglycerolemic subjects

BackgroundLactobacillus gasseri SBT2055 (LG2055) inhibits dietary fat absorption in rats and exerts preventive effects on abdominal adiposity in rats and humans. The present study aimed to evaluate the effects of LG2055 on postprandial serum lipid responses in Japanese subjects with hypertriacylglycerolemia after the intake of oral fat-loading test (OFLT) meals.MethodsWe conducted a single-blind, placebo-controlled, within-subject, repeated-measure intervention trial. Twenty subjects initially ingested the fermented milk (FM) without LG2055 for 4 weeks (control FM period), followed by a 4-week washout period, and then consumed FM containing LG2055 for 4 weeks (active FM period). The subjects were asked to consume FM at 200 g/day. At the end of each 4-week period, an 8-h OFLT was conducted. Blood samples were collected at fasting and every hour for 8 h after OFLT meal intake. Thereafter, postprandial serum non-esterified fatty acid (NEFA) and triacylglycerol (TAG) levels and fasting blood parameters were measured.ResultsThe OFLT showed that the postprandial serum NEFA levels from 120 to 480 min and the postprandial serum TAG level at 120 min in the active FM period were significantly (P < 0.05) lower than those in the control FM period. The fasting serum NEFA level in the active FM period significantly (P < 0.001) decreased at week 4 from the initial period compared with the control FM period.ConclusionsThe consumption of probiotic LG2055 reduced postprandial and fasting serum NEFA levels, suggesting its possible contribution to the reduction of the risk for obesity and type 2 diabetes mellitus.Trial registrationUMIN000011605

Effect of Vaccinium ashei reade Leaves on Angiotensin Converting Enzyme Activity in Vitro and on Systolic Blood Pressure of Spontaneously Hypertensive Rats in Vivo

The hypotensive effects of Vaccinium ashei reade (blueberry) leaves were studied in vitro and in vivo. Blueberry leaf showed a strong inhibitory effect on angiotensin-converting enzyme activity in vitro. Additionally, feeding of blueberry leaf suppressed the development of essential hypertension in spontaneously hypertensive rats in vivo. These results promise the use of blueberry leaf as a source of dietary hypotensive components.

Dietary Fat Influences the Expression of Contractile and Metabolic Genes in Rat Skeletal Muscle

Dietary fat plays a major role in obesity, lipid metabolism, and cardiovascular diseases. To determine whether the intake of different types of dietary fats affect the muscle fiber types that govern the metabolic and contractile properties of the skeletal muscle, we fed male Wistar rats with a 15% fat diet derived from different fat sources. Diets composed of soybean oil (n-6 polyunsaturated fatty acids (PUFA)-rich), fish oil (n-3 PUFA-rich), or lard (low in PUFAs) were administered to the rats for 4 weeks. Myosin heavy chain (MyHC) isoforms were used as biomarkers to delineate the skeletal muscle fiber types. Compared with soybean oil intake, fish oil intake showed significantly lower levels of the fast-type MyHC2B and higher levels of the intermediate-type MyHC2X composition in the extensor digitorum longus (EDL) muscle, which is a fast-type dominant muscle. Concomitantly, MyHC2X mRNA levels in fish oil-fed rats were significantly higher than those observed in the soybean oil-fed rats. The MyHC isoform composition in the lard-fed rats was an intermediate between that of the fish oil and soybean oil-fed rats. Mitochondrial uncoupling protein 3, pyruvate dehydrogenase kinase 4, and porin mRNA showed significantly upregulated levels in the EDL of fish oil-fed rats compared to those observed in soybean oil-fed and lard-fed rats, implying an activation of oxidative metabolism. In contrast, no changes in the composition of MyHC isoforms was observed in the soleus muscle, which is a slow-type dominant muscle. Fatty acid composition in the serum and the muscle was significantly influenced by the type of dietary fat consumed. In conclusion, dietary fat affects the expression of genes related to the contractile and metabolic properties in the fast-type dominant skeletal muscle, where the activation of oxidative metabolism is more pronounced after fish oil intake than that after soybean oil intake.

Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice

BackgroundLipodystrophies are rare acquired and genetic disorders characterized by the complete or partial absence of body fat with a line of metabolic disorders. Previous studies demonstrated that dietary conjugated linoleic acid (CLA) induces hepatic steatosis and hyperinsulinemia through the drastic reduction of adipocytokine levels due to a paucity of adipose tissue in mice and the pathogenesis of these metabolic abnormalities in CLA-fed mice is similar to that in human lipodystrophy. The present study explores the effect of leptin infusion on the pathogenesis of diet-induced lipodystrophy in mice. C57BL/6N mice were assigned to three groups: (1) mice were fed a semisynthetic diet supplemented with 6% corn oil and infused PBS intraperitoneally (normal group), (2) mice were fed a semisynthetic diet supplemented with 4% corn oil plus 2% CLA and infused PBS intraperitoneally (lipodystrophy-control group), and (3) mice were fed a semisynthetic diet supplemented with 4% corn oil plus 2% CLA and infused recombinant murine leptin intraperitoneally (lipodystrophy-leptin group). All mice were fed normal or lipodystrophy model diets for 4 weeks and were infused intrapeneally 0 or 5 μ g of leptin per day from third week of the feeding period for 1 week.ResultsThe results indicate that leptin infusion can attenuate hepatic steatosis and hyperinsulinemia through the reduction of hepatic triglyceride synthesis and the improvement of insulin sensitivity in diet-induced lipodystrophy model mice.ConclusionWe expect the use of this model for clarifying the pathophysiology of lipodystrophy-induced metabolic abnormalities and evaluating the efficacy and safety of drug and dietary treatment.

Effects of Lotus Root (the Edible Rhizome of Nelumbo nucifera) on the Deveolopment of Non-Alcoholic Fatty Liver Disease in Obese Diabetic db/db Mice

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. The discovery of food components that would ameliorate NAFLD is therefore of interest. Lotus root, the edible rhizome of Nelumbo nucifera, contains a high level of polyphenolic compounds, and several health-promoting properties of lotus root have been reported. The present study examines whether dietary lotus root powder can protect db/db mice from hepatic injury. After 3 weeks of feeding, the hepatomegaly, hepatic triglyceride accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in the Lotus diet-fed db/db mice relative to the control mice. These effects were partly attributable to suppression of the lipogenic enzyme activities and mRNA expression by the Lotus diet. The serum levels of adiponectin, which has been reported to have a protective effect against NAFLD, were significantly higher in the Lotus group than in the Control group of the db/db mice. Moreover, the hepatic expression of such inflammatory genes as tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were markedly suppressed by the Lotus diet. We speculate that the development and progression of NAFLD were prevented by suppressing the expression of lipogenic and inflammatory genes as a result of the higher serum adioponectin level in the Lotus diet-fed db/db mice.

Effect of Vaccinium ashei reade leaves on lipid metabolism in Otsuka Long-Evans Tokushima Fatty rats

The effects of blueberry leaf (BBL) on lipid metabolism were studied in obese rats. Feeding of BBL lowered levels of serum lipids and C-reactive protein and alleviated hepatic triglyceride accumulation in the rats. The hypolipidemic effect might be attributable to a reduction of lipogenesis and enhancement of lipolysis in the liver. These results suggest the use of blueberry leaf as a dietary hypolipidemic component.

Dietary Egg White Protein Inhibits Lymphatic Lipid Transport in Thoracic Lymph Duct-Cannulated Rats

Dietary egg white protein (EWP) decreases serum cholesterol levels. We previously showed that EWP decreased cholesterol absorption in the intestine. Rats subjected to permanent lymph duct cannulation were used to investigate the effects of dietary EWP on lipid transport. They were fed diets with 20% EWP and casein, and their lymph was collected to quantify lymphatic lipid levels. Dietary EWP decreased lymphatic cholesterol transport compared with casein. It was previously shown that EWP excluded cholesterol from bile acid micelles. Therefore, pepsin-hydrolyzed EWP and casein were prepared. EWP was not completely digested. Ovalbumin, which is the most abundant protein in EWP, showed resistance to digestion by pepsin. This study investigated the effects of EWP pepsin hydrolysate (EWP-ph) on cholesterol micellar solubility, cholesterol transfer from the micellar to the oil phase, water-holding capacity (WHC), settling volume in water (SV), and relative viscosity and compared them with the effects of casein pepsin hydrolysate (C-ph). EWP-ph significantly decreased the micellar solubility and transfer rate and increased the WHC, SV, and relative viscosity compared with C-ph. Moreover, the pepsin hydrolysate of ovalbumin, a major protein in EWP, played a role in decreasing cholesterol micellar solubility, leading to the inhibition of cholesterol absorption. In conclusion, dietary EWP decreased cholesterol intestinal absorption by exerting combined effects of these physicochemical properties in the gut.