Multi-omics: Differential expression of IFN-γ results in distinctive mechanistic features linking chronic inflammation, gut dysbiosis, and autoimmune diseases.

Low grade, chronic inflammation is a critical risk factor for immunologic dysfunction including autoimmune diseases. However, the multiplicity of complex mechanisms and lack of relevant murine models limit our understanding of the precise role of chronic inflammation. To address these hurdles, we took advantage of multi-omics data and a unique murine model with a low but chronic expression of IFN-γ, generated by replacement of the AU-rich element (ARE) in the 3' UTR region of IFN-γ mRNA with random nucleotides. Herein, we demonstrate that low but differential expression of IFN-γ in mice by homozygous or heterozygous ARE replacement triggers distinctive gut microbial alterations, of which alteration is female-biased with autoimmune-associated microbiota. Metabolomics data indicates that gut microbiota-dependent metabolites have more robust sex-differences than microbiome profiling, particularly those involved in fatty acid oxidation and nuclear receptor signaling. More importantly, homozygous ARE-Del mice have dramatic changes in tryptophan metabolism, bile acid and long-chain lipid metabolism, which interact with gut microbiota and nuclear receptor signaling similarly with sex-dependent metabolites. Consistent with these findings, nuclear receptor signaling, encompassing molecules such as PPARs, FXR, and LXRs, was detectable as a top canonical pathway in comparison of blood and tissue-specific gene expression between female homozygous vs heterozygous ARE-Del mice. Further analysis implies that dysregulated autophagy in macrophages is critical for breaking self-tolerance and gut homeostasis, while pathways interact with nuclear receptor signaling to regulate inflammatory responses. Overall, pathway-based integration of multi-omics data provides systemic and cellular insights about how chronic inflammation driven by IFN-γ results in the development of autoimmune diseases with specific etiopathological features.

IFNγ is a Key Link between Obesity and Th1-Mediated AutoImmune Diseases.

Obesity, a characteristic of metabolic syndrome, is also associated with chronic inflammation and the development of autoimmune diseases. However, the relationship between obesity and autoimmune diseases remains to be investigated in depth. Here, we compared hepatic gene expression profiles among high-fat diet (HFD) mice using the primary biliary cholangitis (PBC) mouse model based on the chronic expression of interferon gamma (IFNγ) (ARE-Del-/- mice). The top differentially expressed genes affected by upstream transcriptional regulators IFNγ, LPS, and TNFα displayed an overlap in HFD and ARE-Del-/- mice, indicating that obesity-induced liver inflammation may be dependent on signaling via IFNγ. The top pathways altered in HFD mice were mostly involved in the innate immune responses, which overlapped with ARE-Del-/- mice. In contrast, T cell-mediated signaling pathways were exclusively altered in ARE-Del-/- mice. We further evaluated the therapeutic effect of luteolin, known as anti-inflammatory flavonoid, in HFD and ARE-Del-/- mice. Luteolin strongly suppressed the MHC I and II antigen presentation pathways, which were highly activated in both HFD and ARE-Del-/- mice. Conversely, luteolin increased metabolic processes of fatty acid oxidation and oxidative phosphorylation in the liver, which were suppressed in ARE-Del-/- mice. Luteolin also strongly induced PPAR signaling, which was downregulated in HFD and ARE-Del-/- mice. Using human GWAS data, we characterized the genetic interaction between significant obesity-related genes and IFNγ signaling and demonstrated that IFNγ is crucial for obesity-mediated inflammatory responses. Collectively, this study improves our mechanistic understanding of the relationship between obesity and autoimmune diseases. Furthermore, it provides new methodological insights into how immune network-based analyses effectively integrate RNA-seq and microarray data.

Quantitative real-time PCR analysis of four genetically modified soybean events using plasmid and genomic DNA calibrators.

A calibration curve is required for reliable and accurate quantitative real-time PCR analysis of genetically modified (GM) organisms, necessitating the use of reference materials as calibrators. In this study, two types of DNA calibrators-plasmid DNA (pDNA) and genomic DNA (gDNA)-were used to quantify four GM soybean events (SYHT0H2, MON87751, DAS-44406-6, and DAS-81419-2). The PCR efficiency and linearity for the calibrators adhered to the CODEX guidelines. The conversion factor (Cf) was calculated as the ratio of copies of GM events to those of endogenous genes using the pDNA calibration curve. To assess the accuracy and repeatability of these assays, quantification at GM levels of 3% and 1% was performed. Based on our results, we believe that the pDNA calibrator assessed in this study can be used as a reference material for GMO quantitative analysis and can replace gDNA, especially considering the ease of management and advantages of mass production. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01392-0.

3-Fucosyllactose-mediated modulation of immune response against virus infection.

Viral pathogens, particularly influenza and SARS-CoV-2, pose a significant global health challenge. Given the immunomodulatory properties of human milk oligosaccharides, in particular 2'-fucosyllactose and 3-fucosyllactose (3-FL), we investigated their dietary supplementation effects on antiviral responses in mouse models. This study revealed distinct immune modulations induced by 3-FL. RNA-sequencing data showed that 3-FL increased the expression of interferon receptors, such as Interferon Alpha and Beta Receptor (IFNAR) and Interferon Gamma Receptor (IFNGR), while simultaneously downregulating interferons and interferon-stimulated genes, an effect not observed with 2'-fucosyllactose supplementation. Such modulation enhanced antiviral responses in both cell culture and animal models while attenuating pre-emptive inflammatory responses. Nitric oxide concentrations in 3-FL-supplemented A549 cells and mouse lung tissues were elevated exclusively upon infection, reaching 5.8- and 1.9-fold increases over control groups, respectively. In addition, 3-FL promoted leukocyte infiltration into the site of infection upon viral challenge. 3-FL supplementation provided protective efficacy against lethal influenza challenge in mice. The demonstrated antiviral efficacy spanned multiple influenza strains and extended to SARS-CoV-2. In conclusion, 3-FL is a unique immunomodulator that helps protect the host from viral infection while suppressing inflammation prior to infection.

Detection method for genetically modified potato using an ultra-fast PCR system.

Genetically modified (GM) potatoes having resistance to insects and viral diseases, low reducing sugar contents, and black spots for high quality continue to be developed. However, no GM potato has been approved as food or feed in the Republic of Korea as the country adheres to a zero-tolerance policy to unauthorized genetically modified organisms (GMOs). When the self-sufficiency rate is low, a detection method to assess GMOs in crops or other products is necessary. Therefore, a rapid method for two GM potato events (SPS-Y9 and EH92-527-1) using an ultra-fast PCR (UF-PCR) system has been developed, and its specificity, sensitivity, and applicability were demonstrated. UF-PCR can decrease the runtime of PCR by more than half of that needed in conventional methods. However, UF-PCR is not a common method for GMO analysis. This rapid detection method may be useful for GMO analyses in field conditions.

2'-Fucosyllactose and 3-Fucosyllactose Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Modulating the Intestinal Microbiome.

Ulcerative colitis is an inflammatory bowel disease (IBD) with relapsing and remitting patterns, and it is caused by varied factors, such as the intestinal inflammation extent and duration. We examined the preventative effects of human milk oligosaccharides (HMOs) on epithelial barrier integrity and intestinal inflammation in an interleukin (IL)-6-induced cell model and dextran sodium sulfate (DSS)-induced acute mouse colitis model. HMOs including 2'-fucosyllactose (FL) and 3-FL and positive controls including fructooligosaccharide (FOS) and 5-acetylsalicylic acid (5-ASA) were orally administrated once per day to C57BL/6J mice with colitis induced by 5% DSS in the administered drinking water. 2'-FL and 3-FL did not affect the cell viability in Caco-2 cells. Meanwhile, these agents reversed IL-6-reduced intestinal barrier function in Caco-2 cells. Furthermore, 2'-FL and 3-FL reversed the body weight loss and the remarkably short colon lengths in DSS-induced acute colitis mice. Moreover, 2'-FL and 3-FL obviously protected the decreasing expression of zonula occluden-1 and occludin in colon tissue relative to the findings in the DSS-treated control group. 2'-FL and 3-FL significantly reduced IL-6 and tumor necrosis factor-α levels in serum relative to the control findings. The summary of these results shows that HMOs prevent colitis mainly by enhancing intestinal barrier function and advancing anti-inflammatory responses. Therefore, HMOs might suppress inflammatory responses and represent candidate treatments for IBD that protect intestinal integrity.

Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2'-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia-Reperfusion Injury.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2'-fucosyllactose (2'-FL), a human milk oligosaccharide, exerts anti-inflammatory effects and plays a protective role in arterial thrombosis; however, its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2'-FL and its potential mechanisms in a mouse model of ischemic stroke. Neurological score and behavior tests revealed that 2'-FL promoted the recovery of neurological deficits and motor function in middle cerebral artery occlusion (MCAO) mice, and that 2'FL led to a reduction in the size of cerebral infarct. Biochemical studies showed that administration of 2'-FL led to a reduction of reactive oxygen species (ROS)-related products in the brain of MCAO mice. 2'-FL upregulated IL-10 and downregulated TNF-α level. In addition, 2'-FL enhanced M2-type microglial polarization and upregulated CD206 expression at 7 days after MCAO. At 3 days after MCAO, 2'-FL increased IL-4 levels and activated STAT6. Our data show that 2'-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type microglial polarization in MCAO mice. These results demonstrate that 2'-FL is a potentially effective therapeutic agent for ischemic stroke.

Development of a rapid detection method for genetically modified rice using the ultra-fast PCR system.

Genetically modified (GM) rice varieties containing traits such as tolerance to abiotic stress and resistance against pests and diseases continue to be developed. However, contamination incidents from unauthorized GM rice varieties have been encountered. To date, no GM rice crop has been authorized for consumption and/or commercialization in Korea. Therefore, to enhance safety management of unauthorized genetically modified organisms (GMOs), accurate and reliable detection methods are needed to identify GMOs in crops or products. In this study, we developed rapid detection methods for GM rice events (Bt63, KMD1, Kefeng6, Kefeng8, and LLRice62) using ultra-fast PCR system. Ultra-fast PCR is a state-of-the-art technology and decreases PCR run-times dramatically. However, the ultra-fast PCR is not widely used in GMO analysis. Thus, we designed a detection method for five events of GM rice and confirmed them by performing specificity, sensitivity, and applicability assays. All results demonstrate that the ultra-fast PCR system is a specific, sensitive, and reliable method to identify and monitor GM rice events. Additionally, it can be utilized as a rapid and simple method for GMO analysis in crops or processed products. This study can be used as a reference for future research on new analysis methods of unauthorized GMOs.

Tannic acid is more effective than clofibrate for the elevation of hepatic ß-oxidation and the inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase and aortic lesion formation in apo E-deficient mice.

The effects of tannic acid (TA) supplementation (0·02 %, wt/wt) were compared with the effects of clofibrate (CF) supplementation (0·02 %, wt/wt) in apo E-deficient (apo E(- / -)) mice fed a AIN-76 semi-synthetic diet (normal diet) over 20 weeks. The mice were monitored for the modulation of hepatic mRNA expression and the activities of lipid-regulating enzymes. Both TA and CF supplementation lowered hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) activity and prevented atherosclerotic lesion formation in comparison with the control group. Hepatic carnitine palmitoyl transferase and ß-oxidation activities were significantly higher in the TA and CF groups than in the control group. Both CF and TA supplementation resulted in significant decreases in hepatic HMGR mRNA levels in association with its enzyme activity. However, in contrast to CF supplementation, TA supplementation seemed to decrease the accumulation of hepatic lipids in the apo E(- / -) mice without increasing liver weight. These results suggest that the overall effect of TA is more desirable than CF for the alleviation of hepatic lipogenesis and atherogenesis in apo E(- / -) mice.

Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial.

BACKGROUND: Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing Glycine max leaves extract (EGML) or Garcinia cambogia extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles. METHODS: Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants. RESULTS: EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group. CONCLUSIONS: Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis.

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat.

BACKGROUND: Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. METHODS: We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. RESULTS: LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. CONCLUSIONS: We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.

Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet.

This study investigated the effects of ursolic acid on immunoregulation and pancreatic beta-cell function in type 1 diabetes fed a high-fat diet for 4 weeks. Male mice were divided into non-diabetic, diabetic control, and diabetic-ursolic acid (0.05%, w/w) groups, which were fed a high-fat (37% calories from fat). Diabetes was induced by injection of streptozotocin (200 mg/kg B.W., i.p.). Ursolic acid significantly improved blood glucose levels, glucose intolerance, and insulin sensitivity compared to the diabetic group. The plasma insulin and C-peptide concentrations were significantly higher in the diabetic-ursolic acid group than in the diabetic group. Ursolic acid significantly elevated the insulin levels with preservation of insulin staining of beta-cells in the pancreas. In splenocytes, concanavalin (Con) A-induced T-cell proliferation was significantly higher in the diabetic-ursolic acid group compared to the diabetic group, but liposaccharide (LPS)-induced B-cell proliferation did not differ between groups. Ursolic acid enhanced IL-2 and IFN-gamma production in response to Con A stimulation, whereas it inhibited TNF-alpha production in response to LPS stimulation. In this study, neither streptozotocin nor ursolic acid had effects on lymphocyte subsets. These results indicate that ursolic acid exhibits potential anti-diabetic and immunomodulatory properties by increasing insulin levels with preservation of pancreatic beta-cells and modulating blood glucose levels, T-cell proliferation and cytokines production by lymphocytes in type 1 diabetic mice fed a high-fat diet.

Antilipogenic effect of green tea extract in C57BL/6J-Lep ob/ob mice.

The objective of this study was to determine the effects of green tea extract (GTE) on lipid metabolism in obese animal models. Male C57BL/6J-Lep ob/ob mice were divided into control and GTE (0.05 g/100 g diet) groups, which were fed a high-fat (20 g/100 g diet) diet for 12 weeks. Supplementation of GTE significantly reduced (p < 0.01) perirenal and total white adipose tissue weights compared with the control group. Also, the plasma HDL-cholesterol level was significantly higher in the GTE group than in the control group, therefore the GTE group showed a higher HDL-cholesterol/total-cholesterol ratio (HTR) and lower atherogenic index (AI) level than the control group. A reduction of hepatic triglyceride content and adipose tissue weight in the GTE group was related to the suppression of enzyme activities for fatty acid synthesis (glucose-6-phosphate dehydrogenase and malic enzyme) without affecting fatty acid oxidation enzyme (beta-oxidation and carnitine palmitoyl transferase) activities in hepatic and adipose tissue. The current results showed that supplementation of green tea extract is beneficial for antiobesity by the suppression of lipogenesis via regulation of related enzyme activities in hepatic and adipose tissue.

Long-term effects of resveratrol supplementation on suppression of atherogenic lesion formation and cholesterol synthesis in apo E-deficient mice.

Atherosclerosis is a chronic inflammatory disease of the arteries resulting from interactions between lipids, monocytes, and arterial wall cells. The effects of resveratrol supplements (RV, 0.02% and 0.06% each, w/w) with regard to the modulation of lipid profiles, cholesterol synthesis, and anti-atherogenesis were examined in apo E-deficient (apo E(-/-)) mice fed a normal diet. The concentration of total-cholesterol (total-C) and LDL-cholesterol (LDL-C) in plasma was significantly lower in the resveratrol-supplemented groups compare to the control group over the entire experimental period. The plasma HDL-C concentration was significantly elevated, and the ratio of HDL-C/total-C was significantly higher in the CF and RV groups than in the control group. Plasma paraoxonase (PON) activity was significantly higher in the 0.06% resveratrol group. The hepatic HMG-CoA reductase (HMGR) activity was significantly lower in the clofibrate and resveratrol groups than in the control group. Resveratrol supplements attenuated the presence of atherosclerotic lesions and periarterial fat deposition in the apo E(-/-) mice. The presence of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in atherosclerotic vessels was diminished in the resveratrol-supplemented apo E(-/-) mice. These results provide new insight into the anti-atherogenic and hypocholesterolemic properties of resveratrol in apo E(-/-) mice that were fed a normal diet.

Anti-obesity and hypolipidemic effects of a proprietary herb and fiber combination (S&S PWH) in rats fed high-fat diets.

The objective of this study was to investigate the effects of S&S PWH, a proprietary herb and fiber combination (Bionutrigen Inc., Daejon, Republic of Korea), on body weight and lipid metabolism in rats fed with a high-fat diet. Three groups of male Sprague-Dawley rats were fed different diets for a 6-week period: normal control diet containing 5% (wt/wt) corn oil (NC group), high-fat diet containing 10% (wt/wt) lard plus 5% (wt/wt) corn oil (HF group), and high-fat diet supplemented with powdered 5% (wt/wt) S&S PWH (S&S PWH group). The body weights and relative weights of the epididymal and perirenal white adipose tissue were significantly lower in the S&S PWH group than in the HF group. S&S PWH supplementation significantly lowered plasma total cholesterol and triglyceride concentrations, whereas it elevated the ratio of high density lipoprotein-cholesterol/total-cholesterol and improved the atherogenic index. The accumulation of hepatic lipid droplets and the epididymal white adipocyte size were less in the S&S PWH group than in the HF group. Hepatic hydroxyl-3-methylglutaryl-coenzyme A reductase and acyl-coenzyme A:cholesterol acyltransferase activities were significantly lower, while adipocyte lipoprotein lipase activity was significantly higher, in the S&S PWH group than in the HF group. These beneficial effects may be due to the combined properties of the phenolic compounds present in high concentrations (1.89 g/100 g) in the S&S PWH. In conclusion, these results suggest that S&S PWH can be considered as an anti-obesity functional formula that is effective for suppressing body weight gain and enhancing lipid profile.

Du-zhong (Eucommia ulmoides Oliver) leaf extract mediates hypolipidemic action in hamsters fed a high-fat diet.

This study examined the effect of a Du-zhong (Eucommia ulmoides Oliver) leaf extract (0.175 g/100 g diet) that was supplemented with a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) on hyperlipidemic hamsters. Hamsters fed with Du-zhong leaf extract for 10 weeks showed a smaller size of epididymal adipocytes compared to the control group. The supplementation of the Du-zhong leaf extract significantly lowered the plasma levels of triglyceride, total cholesterol, LDL-cholesterol, non HDL-cholesterol, and free fatty acid, whereas it elevated the HDL-cholesterol/total cholesterol ratio and apolipoprotein A-I levels. The hepatic cholesterol concentration was lower in the Du-zhong group than in the control group. The plasma total cholesterol concentration was positively correlated with hepatic HMG-CoA reductase activity (r = 0.547, p < 0.05) and hepatic cholesterol concentration (r = 0.769, p < 0.001). The hepatic fatty acid synthase and HMG-CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters. Hepatic fatty acid synthase activity was positively correlated with plasma fatty acid concentration (r = 0.513, p < 0.05) that was lower in the Du-zhong group. These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.

Hypolipidemic effect of dietary diacylglycerol oil in Sprague-Dawley rats fed a normal diet.

The present study compared the effects of dietary diacylglycerol (DG) and triacylglycerol (TG) oil on lipid metabolism in rats fed a 5% fat (AIN-76) diet for 6 weeks. The plasma and hepatic lipids, hepatic cholesterol-regulating enzyme activity, and hepatic and adipose tissue fatty acid metabolism enzyme activities were determined. Among plasma lipids, triglyceride, free fatty acid, and phospholipid concentrations were significantly lower in the DG group than in the TG group. A lower plasma TG level was accompanied by an increase in adipocyte lipoprotein lipase activity. The hepatic triglyceride level was significantly (P < .001) lowered in the DG group, which was attributable to an increased fatty acid oxidation enzyme (beta-oxidation) activity and a reduced fatty acid synthesis enzyme (glucose-6-phosphate dehydrogenase) activity. The plasma cholesterol concentration was significantly lower in the DG group and was accompanied by a lower hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity. The DG oil used in this study was beneficial for enhancing lipid metabolism with apparent hypolipidemic effects.

Effects of soy pinitol on the pro-inflammatory cytokines and scavenger receptors in oxidized low-density lipoprotein-treated THP-1 macrophages.

Pinitol, a methylated form of D-chiro-inositol, acts as a insulin mediator. We investigated the effects of soy pinitol on the factors involved in foam cell formation using differentiated THP-1 macrophages. Pinitol slightly inhibited the lipid-laden foam cell formation by oxidized low-density lipoprotein (oxLDL) in a dose-dependent manner. Tumor necrosis factor-alpha and monocyte chemoattractant protein-1 releases were significantly reduced by pinitol treatment (0.05-0.5 mM), whereas interleukin-1beta and interleukin-8 secretions were significantly reduced in low-dose pinitol (0.05 or 0.1 mM) and 0.5 mM pinitol-treated cells, respectively, compared to no pinitol-treated cells. Gene expressions of CD36 and CD68 were significantly down-regulated by 0.05-0.5 mM pinitol compared to the oxLDL-treated control cells. Matrix metalloproteinase-9 gene expression was significantly decreased in 0.05-0.5 mM pinitol-treated cells compared to the no pinitol-treated macrophages. We conclude that pinitol has some inhibitory effects on foam cell formation by reducing lipid accumulation, secretion, and expression of some cytokines and macrophage scavenger receptor expression via its insulin-like action.

Supplementation of a novel microbial biopolymer, PGB1, from new Enterobacter sp. BL-2 delays the deterioration of type 2 diabetic mice.

Antidiabetic effects of a novel microbial biopolymer (PGB)1 excreted from new Enterobacter sp. BL-2 were tested in the db/db mice. The animals were divided into normal control, rosiglitazone (0.005%, wt/wt), low PGB1 (0.1%, wt/wt), and high PGB1 (0.25%, wt/wt) groups. After 5 weeks, the blood glucose levels of high PGB1 and rosiglitazone supplemented groups were significantly lower than those of the control group. In hepatic glucose metabolic enzyme activities, the glucokinase activities of PGB1 supplemented groups were significantly higher than the control group, whereas the PEPCK activities were significantly lower. The plasma insulin and hepatic glycogen levels of the low and high PGB1 supplemented groups were significantly higher compared with the control group. Specifically, the insulin and glycogen increases were dose-responsive to PGB1 supplement. PGB1 supplement did not affect the IPGTT and IPITT compared with the control group; however, rosiglitazone significantly improved IPITT. High PGB1 and rosiglitazone supplementation preserved the appearance of islets and insulin-positive cells in immunohistochemical photographs of the pancreas compared with the control group. These results demonstrated that high PGB1 (0.25% in the diet) supplementation seemingly contributes to preventing the onset and progression of type 2 diabetes by stimulating insulin secretion and enhancing the hepatic glucose metabolic enzyme activities.

Naringin time-dependently lowers hepatic cholesterol biosynthesis and plasma cholesterol in rats fed high-fat and high-cholesterol diet.

The flavonoid naringin was investigated for its differential effects on hepatic cholesterol regulation when supplemented for 3 weeks and 6 weeks. Sprague-Dawley rats were fed a high-fat and high-cholesterol diet with or without 0.02% naringin supplement for 3 or 6 weeks. Supplementation with naringin resulted in a significant decrease in the plasma cholesterol and triglyceride concentrations in the 6-week trial. Although high-density lipoprotein (HDL)-cholesterol was not altered in either trial, the HDL-cholesterol/total cholesterol ratio (in percent) was significantly higher, and the atherogenic index was significantly lower in the naringin-supplemented groups in the 6-week trial. The hepatic cholesterol content was also lowered by naringin supplementation only in the 6-week trial. The hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was lower in the rats supplemented with naringin for 6 weeks, while the hepatic acyl-coenzyme A:cholesterol acyltransferase activity was lower in both the 3-week and 6-week trials. Results indicate that supplementation with naringin for 3 weeks did not exhibit a hypolipidemic effect when given with a HFHC diet. Naringin can, however, be beneficial for lowering hepatic cholesterol biosynthesis and levels of plasma lipids when supplemented for 6 weeks in this animal model.