Dietary lysophospholipids reduce lymphatic cholesterol transport compared with dietary phospholipids in thoracic lymph-duct cannulated rats.

Dietary phospholipids have been traditionally known to affect micelle formation. Egg yolk-derived lysophospholipids (LysoPL) are commercially available. We investigated the effects of dietary LysoPL on lymphatic lipid transport. We also compared sn-1 LysoPL and sn-2 LysoPL, which have different fatty acyl esterification positions. Thoracic lymph duct-cannulated rats were fed a diet supplemented with egg yolk-derived sn-1 LysoPL, sn-2 LysoPL, or phospholipids (PL). The amount of lymphatic lipid transport was also evaluated. Time courses of transport were applied to the one-compartment model as one of the pharmacokinetic analyses. The solubility of cholesterol in bile acid micelles was measured. Compared to the PL diet, the sn-1 and sn-2 LysoPL diets significantly reduced the lymphatic transport of cholesterol. There were no differences in the lymphatic PL and TAG transport. There was no difference in cholesterol transport between the sn-1 LysoPL group and the sn-2 LysoPL group; however, the transport rate constant at a decrease in lymphatic cholesterol was lower in the sn-1 LysoPL group than in the sn-2 LysoPL group. Cholesterol solubility in bile acid micelles was significantly decreased in the sn-1 LysoPL and sn-2 LysoPL groups compared to that in the PL group. Dietary LysoPL affects the behavior of intestinal cholesterol and suppresses lymphatic cholesterol transport.

Dietary egg white protein hydrolysate improves orotic acid-induced fatty liver in rats by promoting hepatic phospholipid synthesis and microsomal triglyceride transfer protein expression.

We investigated the effects of egg white protein hydrolysates (EWH) on orotic acid (OA)-induced nonalcoholic fatty liver (NAFL) in rats. Effects of the egg white protein (EWP) and EWH were also compared. Four groups of male Sprague-Dawley rats were separately fed AIN-76-based diets, supplemented with 20% casein for control, or with 1% OA, together with either 20% casein (OA), 20% EWP, or 20% EWH, respectively, for 3 d (developing stage) and 14 d (developed stage). In both feeding periods, animals from the OA group showed higher accumulation hepatic triacylglycerol (TAG) compared with those from the control group. In the 14-d experiment, dietary EWP and EWH significantly reduced the hepatic TAG levels. Intake of EWP reduced liver fat in OA-fed rats by 61%, while EWH reduced it by 92%. In addition, EWH restored the OA-induced high serum-TAG level to that seen in the control group. The 3 d experiment showed that consumption of EWH improved the expression of hepatic MTP, that was reduced by OA, without changing Mttp gene expression. It also increased the hepatic synthesis of PC and PE by enhancing the transcription of Pcyt1 and Pemt genes. Inclusion of EWP and EWH in the diet improves the OA-induced NAFL. EWH reduces the liver TAG better than EWP, and works more rapidly. Dietary EWH ameliorates OA-induced NAFL by promoting the secretion of hepatic TAG.

12α-Hydroxylated bile acid induces hepatic steatosis with dysbiosis in rats.

There is an increasing need to explore the mechanism of the progression of non-alcoholic fatty liver disease. Steroid metabolism is closely linked to hepatic steatosis and steroids are excreted as bile acids (BAs). Here, we demonstrated that feeding WKAH/HkmSlc inbred rats a diet supplemented with cholic acid (CA) at 0.5 g/kg for 13 weeks induced simple steatosis without obesity. Liver triglyceride and cholesterol levels were increased accompanied by mild elevation of aminotransferase activities. There were no signs of inflammation, insulin resistance, oxidative stress, or fibrosis. CA supplementation increased levels of CA and taurocholic acid (TCA) in enterohepatic circulation and deoxycholic acid (DCA) levels in cecum with an increased ratio of 12α-hydroxylated BAs to non-12α-hydroxylated BAs. Analyses of hepatic gene expression revealed no apparent feedback control of BA and cholesterol biosynthesis. CA feeding induced dysbiosis in cecal microbiota with enrichment of DCA producers, which underlines the increased cecal DCA levels. The mechanism of steatosis was increased expression of Srebp1 (positive regulator of liver lipogenesis) through activation of the liver X receptor by increased oxysterols in the CA-fed rats, especially 4ß-hydroxycholesterol (4ßOH) formed by upregulated expression of hepatic Cyp3a2, responsible for 4ßOH formation. Multiple regression analyses identified portal TCA and cecal DCA as positive predictors for liver 4ßOH levels. The possible mechanisms linking these predictors and upregulated expression of Cyp3a2 are discussed. Overall, our observations highlight the role of 12α-hydroxylated BAs in triggering liver lipogenesis and allow us to explore the mechanisms of hepatic steatosis onset, focusing on cholesterol and BA metabolism.

Soy ß-Conglycinin Peptide Attenuates Obesity and Lipid Abnormalities in Obese Model OLETF Rats.

We previously reported that soy ß-conglycinin (ßCG) improves obesity-induced metabolic abnormalities, but not obesity, in obese model Otsuka Long-Evans Tokushima fatty (OLETF) rats. In the present study, we aimed to investigate the effects of ßCG-derived peptide consumption on obesity and lipid abnormality in OLETF rats. To this end, wild-type Long-Evans Tokushima Otsuka and OLETF rats were provided a normal diet containing 20% casein for four weeks as a control. In addition, we prepared ßCG peptide by enzymatic hydrolysis, and OLETF rats were fed a diet in which half of the casein was replaced by ßCG peptide (ßCG peptide group). Consequently, rats in the ßCG peptide group showed decreased abdominal white adipose tissue weight and lipid content (serum and liver triglycerides, and serum and liver cholesterol) compared to control OLETF rats. Further analysis demonstrated that ßCG peptide consumption decreased lipogenic enzyme activity and increased lipolytic enzyme activity in the liver of OLETF rats. In addition, suppressive effects on both synthesis and absorption of cholesterol were observed in ßCG peptide-fed OLETF rats. These findings suggest that peptidization of ßCG enhanced the anti-obese and hypolipidemic effects of ßCG.

Treatment with myo-inositol attenuates binding of the carbohydrate-responsive element-binding protein to the ChREBP-ß and FASN genes in rat nonalcoholic fatty liver induced by high-fructose diet.

Dietary supplementation with the major lipotrope myo-inositol (MI) potently reduces triglyceride (TG) content and expression levels of the fatty acid synthesis genes, for example, fatty acid synthase (FASN), in rat nonalcoholic fatty liver induced by high-fructose diet. Fatty acid synthesis genes are regulated by the carbohydrate-responsive element-binding protein (ChREBP) that exists in 2 isoforms: ChREBP-α and ChREBP-ß. The gene encoding the latter isoform is more responsive to fructose. Because MI repressed the induction of fatty acid synthesis gene expression by high-fructose diet, we hypothesized that MI may reduce binding of ChREBP to the carbohydrate response elements (ChoREs) in the ChREBP-ß gene as well as in fatty acid synthesis genes in the liver. Rats were fed high-glucose, high-fructose, or high-fructose diets supplemented with MI (0.05% and 0.25%) for 2 weeks. Hepatic TG content and expression levels of the glucose-6-phosphate dehydrogenase, malic enzyme 1, FASN, acetyl-CoA carboxylase alpha, S14, and ChREBP-ß were remarkably elevated in rats fed with high fructose compared with the corresponding levels in high-glucose group. Notably, elevated values of these parameters in high-fructose group were reduced by MI. Similarly, high-fructose-induced ChREBP binding to the ChoREs of the ChREBP-ß and FASN genes was nominally decreased by MI. This study showed that treatment with MI reduced elevated TG content and expression of genes related to fatty acid synthesis, such as FASN and ChREBP-ß, in rat nonalcoholic fatty liver induced by high-fructose diet. Furthermore, MI treatment nominally decreased increased binding of ChREBP to the ChoREs of ChREBP-ß and FASN genes.

Dietary Sparassis crispa Reduces Body Fat Mass and Hepatic Lipid Levels by Enhancing Energy Expenditure and Suppressing Lipogenesis in Rats.

Accumulation of abdominal fat triggers metabolic syndrome, which is a cluster of metabolic abnormalities, such as dyslipidemia, glucose intolerance, insulin resistance or hyperinsulinemia, and hypertension, that leads to the development of diabetes and cardiovascular disease. Mushrooms have been used as a foodstuff and folk medicine worldwide. Among these mushrooms, Sparassis crispa (SC) is a relatively newly cultivated edible and medicinal mushroom, which has been reported to have anti-diabetic and anti-hypertensive properties. However, little is known about the anti-obesity and anti-hyperlipidemic properties of SC. In the present study, we investigated the effects of dietary SC on lipid metabolism and energy expenditure in Sprague-Dawley rats with diet-induced obesity and diabetes, and conducted respiratory gas analysis to determine how energy metabolism is altered by SC. After feeding periods of 3 and 7 weeks, dietary SC had significantly reduced hepatic triacylglycerol and cholesterol contents in a dose-dependent manner. These changes were attributable to suppression of fatty acid and cholesterol synthesis in the liver and increased insulin sensitivity in the body. In addition, after a feeding period of 6 weeks, dietary SC significantly increased energy expenditure through carbohydrate oxidation, reducing abdominal fat mass after 7 weeks. In conclusion, our results indicate that in addition to the previously reported anti-diabetic and anti-hypertensive activities, dietary SC exhibits anti-obesity and anti-hyperlipidemic activities that help protect against metabolic syndrome.

Anti-obesity activity of Yamabushitake (Hericium erinaceus) powder in ovariectomized mice, and its potentially active compounds.

Hericium erinaceus (H. erinaceus) improves the symptoms of menopause. In this study, using ovariectomized mice as a model of menopause, we investigated the anti-obesity effect of this mushroom in menopause. Mice fed diets containing H. erinaceus powder showed significant decreases in the amounts of fat tissue, plasma levels of total cholesterol, and leptin. To determine the mechanism, groups of mice were respectively fed a diet containing H. erinaceus powder, a diet containing ethanol extract of H. erinaceus, and a diet containing a residue of the extract. As a result, H. erinaceus powder was found to increase fecal lipid levels in excreted matter. Further in vitro investigation showed that ethanol extract inhibited the activity of lipase, and four lipase-inhibitory compounds were isolated from the extract: hericenone C, hericenone D, hericenone F, and hericenone G. In short, we suggest that H. erinaceus has an anti-obesity effect during menopause because it decreases the ability to absorb lipids.

Inhibitory effects of the leaves of loquat (Eriobotrya japonica) on bone mineral density loss in ovariectomized mice and osteoclast differentiation.

The loquat, Eriobotrya japonica Lindl. (Rosaceae), is a small tree native to Japan and China that is widely cultivated for its succulent fruit. Its leaves are used as an ingredient of a tasty tea called "Biwa cha" in Japanese. The anti-osteoporosis effects of the leaves of loquat in vitro and in vivo have been investigated. After 15 days of feeding normal diet or diet supplemented with 5% loquat leaves, the body weight, viscera weights, and bone mineral density (BMD) of both groups of eight ovariectomized (OVX) mice were compared. The result showed that the loss of BMD in loquat-fed mice was significantly prevented in three parts of the body, especially in the trabecular bone of the head (P < 0.05), abdomen (P < 0.01), and lumbar (P < 0.05) compared to the control group. No hypertrophy in the uterus by the loquat leaves diet was observed. The effect of the extract (447.25 g) prepared from the dried leaves of loquat (2.36 kg) was further studied on RANKL-induced osteoclast differentiation and cell viability. The extract suppressed the differentiation of osteoclasts under 50, 125, 250, and 500 µg/mL. Through bioactivity-guided fractionation, ursolic acid (1) was isolated and inhibited osteoclast differentiation under 4 and 10 µg/mL. It was concluded that loquat leaves possess the potential to suppress ovariectomy-induced bone mineral density deterioration.

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 Mukitake mushroom (Panellus serotinus) on the pathogenesis of lipid abnormalities in obese, diabetic ob/ob mice.

BACKGROUND: Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries, and several compounds that modulate the immune system, lower blood lipid levels, and inhibit tumor and viral action have been isolated. The fruiting body of Panellus serotinus (Mukitake) is recognized in Japan as one of the most delicious edible mushrooms, and previous studies have demonstrated that the dietary intake of powdered whole Mukitake or Mukitake extracts prevents the development of non-alcoholic fatty liver disease (NAFLD) in leptin-resistant db/db mice. In the present study, we evaluated the effect of the Mukitake diet on the pathogenesis of metabolic disorders in leptin-deficient ob/ob mice. RESULTS: After 4 weeks of feeding, hepatomegaly, hepatic lipid accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in Mukitake-fed ob/ob mice compared with control mice. Moreover, the mild hyperlipidemia in control ob/ob mice was attenuated and the elevated atherogenic index was reduced in Mukitake-fed ob/ob mice. These effects were partly attributable to the suppression of hepatic lipogenic enzyme activity due to the Mukitake diet. CONCLUSION: The current results showed that Mukitake supplementation is beneficial for the alleviation of NAFLD and dyslipidemia in obese, diabetic ob/ob mice.

Supplementation of highly concentrated ß-cryptoxanthin in a satsuma mandarin beverage improves adipocytokine profiles in obese Japanese women.

BACKGROUND: Serum ß-cryptoxanthin levels are lower in overweight subjects than in normal subjects. Abnormalities of adipocytokine profiles in obesity subjects have been reported. There are several reports that serum ß-cryptoxanthin levels in them were relatively lower than normal subjects. OBJECTIVE: We hypothesize that supplementation of highly concentrated ß-cryptoxanthin improves serum adipocytokine profiles in obese subjects. This study tested the association between ß-cryptoxanthin intake and serum adipocytokine levels. METHODS: An intervention study consisted of a 3-week long before-and-after controlled trial, where ß-cryptoxanthin (4.7 mg/day) was given to 17 moderately obese postmenopausal women. RESULTS: The results indicated no significant changes in body weight or body mass index (BMI). Serum ß-cryptoxanthin levels increased significantly by 4-fold. Serum high molecular weight (HMW)-adiponectin levels increased significantly, while serum plasminogen activator inhibitor (PAI)-1 levels decreased. CONCLUSIONS: We concluded that increasing the intake of ß-cryptoxanthin to approximately 4 mg per day for 3 weeks may have beneficial effects on the serum adipocytokine status and consequently alleviate progression of metabolic syndrome.

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.

Protective effects of fractional extracts from Panellus serotinus on 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 industrialised countries. Various mushrooms have been used in Eastern folk medicine for the treatment of lifestyle diseases. We previously found that the dietary intake of powdered whole Panellus serotinus (Mukitake) alleviates NAFLD in obese, diabetic db/db mice. In the present study, we investigated the influence of Mukitake fractional extracts on the development of NAFLD in db/db mice. A significant reduction in the hepatic TAG content, macrovesicular hepatocytes and activities of key enzymes for de novo synthesis of the fatty acid was observed in both the water-soluble Mukitake extract (WE) diet and the ethanol-soluble Mukitake extract (EE) diet groups compared with the control diet group of the db/db mice. The serum level of monocyte chemoattractant protein-1 (MCP-1), which is known to exacerbate insulin resistance, was significantly decreased in the WE group. On the other hand, the serum level of adiponectin, which plays a protective role against the metabolic syndrome, was significantly increased in the EE group. Additionally, differential analysis between Mukitake and Shiitake, mycelia from the same family, using liquid chromatography time-of-flight MS technology revealed that only seven and five compounds exist in WE and EE from Mukitake, respectively. In conclusion, the present study demonstrated that Mukitake displays at least two different physiological actions that alleviate NAFLD: one through the reduction in inflammatory damage by its suppression in MCP-1 production and the other through an increase in level of serum adiponectin and the prevention of visceral fat accumulation.

Effect of Vaccinium ashei reade leaf extracts on lipid metabolism in obese OLETF rats.

The effects of a hot water extract and fractional extracts from rabbiteye blueberry (Vaccinium ashei reade) leaves (BBL) on lipid metabolism were studied in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Feeding the hot water extract and fractional extracts from BBL alleviated hepatic triglyceride accumulation in the rats. Additionally, feeding with the flavonol glycoside (FG) and proanthocyanidin (PA) fractions lowered serum cholesterol levels in the obese rats. The results from measurements of the hepatic enzyme activity indicate that the hypolipidemic effects of the hot water extract and the PA fraction might be attributable to enhanced lipolysis in the liver. The reduced serum levels of C-reactive protein, an inflammatory cytokine, by the chlorogenic acid + rutin fraction and FG fraction might be associated with alleviating the metabolic abnormalities in obese rats. These results indicate that the BBL extracts, and especially FG and PA, exerted hypolipidemic effects on obese OLETF rats and suggest that an infusion of BBL can be useful as a dietary hypolipidemic component.

Dietary kakrol (Momordica dioica Roxb.) flesh inhibits triacylglycerol absorption and lowers the risk for development of fatty liver in rats.

Kakrol (Momordica dioica Roxb.) is a cucurbitaceous vegetable native to India and Bangladesh. Bitter gourd (Momordica charantia Linn.), a species related to kakrol, has been shown to have pharmacological properties including antidiabetic and antisteatotic effects. In this study, we investigated the effect of dietary kakrol on lipid metabolism in rats. Sprague-Dawley rats were fed AIN-76 formula diets containing 3% freeze-dried powders of whole kakrol or bitter gourd for two weeks. Results showed significantly lowered liver cholesterol and triacylglycerol levels in rats fed on both diets. Fecal lipid excretion increased in rats fed the kakrol diet, and lymphatic transport of triacylglycerol and phospholipids decreased in rats fed the kakrol diet after permanent lymph cannulation. Furthermore, n-butanol extract from kakrol caused a significant concentration-dependent decrease in the pancreatic lipase activity in vitro. These results indicate that the mechanisms of action on lipid metabolism in kakrol and bitter gourd are different and that dietary kakrol reduces liver lipids by inhibiting lipid absorption.

Physiological functions of iso-type short-chain fatty acid and omega 3 polyunsaturated fatty acids containing oil in obese OLETF rats.

It has been known that tissues of porpoise contain unique structured-lipids as combination of iso-valeric acid (iso-C5:0) and omega 3 polyunsaturated fatty acids (omega3 PUFAs). It is well known that omega3 PUFAs have lipid-lowering effects in animal and human studies. Although branched chain fatty acids have been interested in their unique functions, there is no data concerning the effect of iso-C5:0 on lipid metabolism. In this study we investigated the effect of structured-lipids from porpoise adipose tissue (porpoise oil) on lipid metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. For 4 weeks, rats were fed semisynthetic diets containing either 10% corn oil or 5% corn oil plus 5% porpoise oil. After feeding period, the porpoise oil diet significantly alleviated hepatic triglyceride accumulation compared with the control diet in OLETF rats. Although serum triglyceride level increased, serum level of adiponectin that can protect liver function and alleviate abnormalities of lipid and glucose metabolism increased in rats fed porpoise oil diet. In conclusion, results from the present study suggest that porpoise oil feeding prevents the development of fatty liver disease through the enhancement of lipoprotein secretion and increase of adiponectin production in obese rats.

Mukitake mushroom (Panellus serotinus) alleviates nonalcoholic fatty liver disease through the suppression of monocyte chemoattractant protein 1 production in db/db mice.

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Thus, the discovery of food components that would ameliorate NAFLD is of interest. Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries and several compounds that modulate immune system, lower blood lipid levels, inhibit tumor and viral action have been isolated from them. In this study, we tested whether feeding Panellus serotinus (Mukitake) to db/db mice protects them from hepatic injury. After 4 weeks of feeding, hepatomegaly, hepatic triglyceride accumulation and elevated hepatic injury markers in serum were markedly alleviated in Mukitake-fed db/db mice compared with control mice. These effects were partly attributable to the enhancement of lipolytic enzyme activity and the suppression of lipogenic enzyme activities due to the Mukitake diet. The severe hyperinsulinemia in control db/db mice tended to attenuate in Mukitake-fed mice due to an enhanced production of adiponectin, which improves insulin sensitivity. Moreover, production of monocyte chemoattractant protein 1 (MCP1), an inflammatory cytokine, was markedly suppressed by the Mukitake diet. In addition, water-soluble extracts of Mukitake powder showed an inhibitory effect on inhibitor of kappaB (IkappaB) kinase (IKK) beta, whose activation is required for nuclear factor kappaB (NFkappaB)-mediated inflammatory response. We speculate that the development and progression of NAFLD was prevented by the reduction of MCP1 production through the interference in the IKKbeta-NFkappaB signaling pathway in Mukitake-fed db/db mice.

Effect of dietary phosphatidylinositol on cholesterol metabolism 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 widespread and increasingly prevalent diseases in industrialized countries. In the present study, we evaluated that the effect of dietary PI on cholesterol metabolism in metabolic syndrome model Zucker (fa/fa) rats. For 4 weeks, rats were fed semisynthetic diets containing either 7% soybean oil or 5% soybean oil plus 2% PI. Dietary PI prevented the mild hypercholesterolemia and hepatic cholesterol accumulation in Zucker (fa/fa) rats. These effects were attributable to an increased fecal bile acid excretion and to the tendencies of decreased ACAT1 mRNA level and increased CYP7A1 mRNA level in the liver. Additionally, dietary PI markedly increased microsomal PI content in the liver of Zucker (fa/fa) rats. Our study suggests that dietary PI normalizes cholesterol metabolism through the enhancement of fecal bile acid excretion in the metabolic syndrome model rats.

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

BACKGROUND: Lipodystrophies 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 mug of leptin per day from third week of the feeding period for 1 week. RESULTS: The 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. CONCLUSION: We 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.

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.