Yunsook Lim

Scavenger receptor class B type I: a multifunctional receptor

The scavenger receptor class B type I (SR‐B1) plays an important role in meditating the uptake of HDL‐derived cholesterol and cholesteryl ester in the liver and steroidogenic tissues. In addition to being ubiquitous, SR‐B1 is a high‐density lipoprotein (HDL) receptor in many tissues, though the mechanism by which SR‐B1 does this is unclear. Other than its role as an HDL receptor, SR‐B1 is also involved in pathogen recognition; its expression can be modulated by lipopolysaccharide and oxidative stress; and it plays a significant role in the uptake of lipid soluble vitamins, such as vitamin E and carotenoids. In this short review, we have summarized the biological aspects to which SR‐B1 has been thus far associated.

Resveratrol ameliorates hepatic metaflammation and inhibits NLRP3 inflammasome activation

OBJECTIVE Resveratrol (RSV) regulates NAD bioavailability and sirtuin-related metabolism, which relates to aging, metabolic syndrome and non-alcoholic fatty liver disease. The purpose of this study was to investigate the effects of resveratrol on hepatic metaflammation in a rodent model of high-fat (HF) diet-induced obesity (DIO). MATERIALS/METHODS DIO was induced in a subset of mice given an HF diet (45% kcal fat). After 6weeks of HF diet feeding, RSV was delivered via an osmotic pump for 4weeks. The experimental groups were as follows: 1) lean control fed with a standard diet, 2) HF diet-induced obese control, and 3) HF_RSV (8mg/kg/day). After 4weeks of each treatment, blood and liver tissues were collected and the indices of glucose control, serum and liver triglyceride (TG), sirtuin pathway, inflammation, and NOD-like receptor family, pryin domain containing 3 (NLRP3) inflammasome were analyzed. RESULTS Body weight and food intake were not altered by administering resveratrol. Glucose control was impaired, and serum and liver TG levels were increased by the HF diet. Hepatic inflammation was aggravated in mice fed with the HF diet, as shown by the increased levels of the pro-inflammatory markers interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha in the liver. However, resveratrol administration significantly improved glucose control, and serum and liver TG contents. Also, resveratrol treatment reduced the levels of the pro-inflammatory markers. These improvements were accompanied by alterations in sirtuin pathway and NLRP3 inflammasome activation. CONCLUSION These results demonstrate that resveratrol ameliorates hepatic metaflammation, accompanied by alterations in NLRP3 inflammasome.

Ozonated sesame oil enhances cutaneous wound healing in SKH1 mice.

Ozone is well recognized as a bactericidal agent and its beneficial effect on wound healing could be a consequence of this property. Because ozone itself does not penetrate the cells but immediately reacts with polyunsaturated fatty acids, its effects should be the results of oxidative reaction. For this reason, ozonated oils could be a way to deliver ozone messengers to the skin. This paper evaluated the therapeutic effects of three different grades of ozonated sesame oil in acute cutaneous wounds made in the skin of SKH1 mice. Specifically, wound closure rate, histological parameters, and the level of key proteins such as vascular endothelial growth factors and cyclin D1 have been analyzed in relation to the peroxide level present in the ozonated oil. Treatment with moderately ozonated sesame oil—expressed as peroxide value about 1,500)—has a faster wound closure rate in the first 7 days than treatment with oil containing either lower or higher peroxide value, and even with controls. Moreover, under the same treatment, an earlier and higher response of cells involved in wound repair, a higher angiogenesis, as well as an enhanced vascular endothelial growth factors and cyclin D1 expression were observed. The present study shows the validity of ozonated sesame oil in cutaneous wound healing and emphasizes the importance of the ozonation grade.

Calorie Restriction with a High-Fat Diet Effectively Attenuated Inflammatory Response and Oxidative Stress-Related Markers in Obese Tissues of the High Diet Fed Rats

Obesity characterized by increased mass of adipose tissue leads to systemic inflammation. Calorie restriction (CR) improves parameters associated with immune response and antioxidant defense. We hypothesized that CR with a high fat diet (HFCR) regulates local and systemic inflammation and oxidative stress damage in a high fat diet induced obesity (HF group). We investigated effect of HFCR on inflammation and oxidative stress-related markers in liver and adipose tissues as well as adipokines in plasma. HFCR lowered liver triglyceride levels, total cholesterol levels, and the plasma leptin/adiponectin ratio to normal levels and improved glucose tolerance. HFCR also improved fatty liver and normalized adipocyte size and morphology. HFCR reduced lipid peroxidation and decreased the expression levels of inducible nitric oxide synthetase, cyclooxygenase-2, NF-E2-related factor, and heme oxygenase-1 in the liver. Moreover, HFCR suppressed the expression levels of C- reactive protein and manganese superoxide dismutase in the adipose tissue in the HF group. These results suggest that HFCR may have beneficial effects on inflammation and oxidative stress as well as lipid profiles in the HF diet induced obesity. Moreover, HFCR may be a good way to increase compliance in obese patients and to prevent obesity induced complications without changes in dietary pattern.

Anti-inflammatory and antiobesity effects of mulberry leaf and fruit extract on high fat diet-induced obesity

The purpose of this study was to investigate the anti-inflammatory and antiobesity effect of combinational mulberry leaf extract (MLE) and mulberry fruit extract (MFE) in a high-fat (HF) diet-induced obese mice. Mice were fed a control diet or a HF diet for nine weeks. After obesity was induced, the mice were administered with single MLE at low dose (133 mg/kg/day, LMLE) and high dose (333 mg/kg/day, HMLE) or combinational MLE and MFE (MLFE) at low dose (133 mg MLE and 67 mg MFE/kg/day, LMLFE) and high dose (333 mg MLE and 167 mg MFE/kg/day, HMLFE) by stomach gavage for 12 weeks. The mulberry leaf and fruit extract treatment for 12 weeks did not show liver toxicity. The single MLE and combinational MLFE treatments significantly decreased plasma triglyceride, liver lipid peroxidation levels and adipocyte size and improved hepatic steatosis as compared with the HF group. The combinational MLFE treatment significantly decreased body weight gain, fasting plasma glucose and insulin, and homeostasis model assessment of insulin resistance. HMLFE treatment significantly improved glucose control during intraperitoneal glucose tolerance test compared with the HF group. Moreover, HMLFE treatment reduced protein levels of oxidative stress markers (manganese superoxide dismutase) and inflammatory markers (monocyte chemoattractant protein-1, inducible nitric oxide synthase, C-reactive protein, tumour necrosis factor-α and interleukin-1) in liver and adipose tissue. Taken together, combinational MLFE treatment has potential antiobesity and antidiabetic effects through modulation of obesity-induced inflammation and oxidative stress in HF diet-induced obesity.

Dieckol, a phlorotannin isolated from a brown seaweed, Ecklonia cava, inhibits adipogenesis through AMP-activated protein kinase (AMPK) activation in 3T3-L1 preadipocytes.

In this study, we assessed the potential inhibitory effect of 5 species of brown seaweeds on adipogenesis the differentiation of 3T3-L1 preadipocytes into mature adipocytes by measuring Oil-Red O staining. The Ecklonia cava extract tested herein evidenced profound adipogenesis inhibitory effect, compared to that exhibited by the other four brown seaweed extracts. Thus, E. cava was selected for isolation of active compounds and finally the three polyphenol compounds of phlorotannins were obtained and their inhibitory effect on adipogenesis was observed. Among the phlorotannins, dieckol exhibited greatest potential adipogenesis inhibition and down-regulated the expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding proteins (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1) and fatty acid binding protein 4 (FABP4) in a dose-dependent manner. The specific mechanism mediating the effects of dieckol was confirmed by AMP-activated protein kinase (AMPK) activation. These results demonstrate inhibitory effect of dieckol compound on adipogenesis through the activation of the AMPK signal pathway.

Combined Treatment of Mulberry Leaf and Fruit Extract Ameliorates Obesity-Related Inflammation and Oxidative Stress in High Fat Diet-Induced Obese Mice

The aim of this study was to investigate whether a combined treatment of mulberry leaf extract (MLE) and mulberry fruit extract (MFE) was effective for improving obesity and obesity-related inflammation and oxidative stress in high fat (HF) diet-induced obese mice. After obesity was induced by HF diet for 9 weeks, the mice were divided into eight groups: (1) lean control, (2) HF diet-induced obese control, (3) 1:1 ratio of MLE and MFE at doses of 200 (L1:1), (4) 500 (M1:1), and (5) 1000 (H1:1) mg/kg per day, and (6) 2:1 ratio of MLE and MFE at doses of 200 (L2:1), (7) 500 (M2:1), and (8) 1000 (H2:1) mg/kg per day. All six combined treatments significantly lowered body weight gain, plasma triglycerides, and lipid peroxidation levels after the 12-week treatment period. Additionally, all combined treatments suppressed hepatic fat accumulation and reduced epididymal adipocyte size. These improvements were accompanied by decreases in protein levels of proinflammatory markers (tumor necrosis factor-alpha, C-reactive protein, interleukin-1, inducible nitric oxide synthase, and phospho-nuclear factor-kappa B inhibitor alpha) and oxidative stress markers (heme oxygenase-1 and manganese superoxide dismutase). M2:1 was the most effective ratio and dose for the improvements in obesity, inflammation, and oxidative stress. These results demonstrate that a combined MLE and MFE treatment ameliorated obesity and obesity-related metabolic stressors and suggest that it can be used as a means to prevent and/or treat obesity.

Short term supplementation of dietary antioxidants selectively regulates the inflammatory responses during early cutaneous wound healing in diabetic mice

BackgroundDiabetic foot ulcers are serious complications for diabetic patients, yet the precise mechanism that underlines the treatment of these diabetic complications remains unclear. We hypothesized that dietary antioxidant supplementation with vitamin C, combined either with vitamin E or with vitamin E and NAC, improves delayed wound healing through modulation of blood glucose levels, oxidative stress, and inflammatory response.MethodsDiabetes was induced by administration of alloxan monohydrate. Mice were divided into 4 groups; CON (non-diabetic control mice fed AIN 93 G purified rodent diet), DM (diabetic mice fed AIN 93 G purified rodent diet), VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet), and Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E, and 2.5% NAC supplemented diet). After 10 days of dietary antioxidant supplementation, cutaneous full-thickness excisional wounds were performed, and the rate of wound closure was examined. TBARS as lipid peroxidation products and vitamin E levels were measured in the liver. Expression levels of oxidative stress and inflammatory response related proteins were measured in the cutaneous wound site.ResultsDietary antioxidant supplementation improved blood glucose levels and wound closure rate and increased liver vitamin E, but not liver TBARS levels in the diabetic mice as compared to those of the CON. In addition, dietary antioxidant supplementation modulated the expression levels of pIκBα, HO-1, CuZnSOD, iNOS and COX-2 proteins in the diabetic mice.ConclusionsThese findings demonstrated that delayed wound healing is associated with an inflammatory response induced by hyperglycaemia, and suggests that dietary antioxidant supplementation may have beneficial effects on wound healing through selective modulation of blood glucose levels, oxidative stress, and inflammatory response.

Severe Vitamin E deficiency modulates airway allergic inflammatory responses in the murine asthma model

Allergic asthma is a complex immunologically mediated disease associated with increased oxidative stress and altered antioxidant defenses. It was hypothesized that α-tocopherol (α-T) decreases oxidative stress and therefore its absence may influence allergic inflammatory process, a pathobiology known to be accompanied by oxidative stress. Therefore, selected parameters of allergic asthma sensitization and inflammation were evaluated following ovalbumin sensitization and re-challenge of α-T transfer protein (TTP) knock-out mice (TTP−/−) that have greatly reduced lung α-T levels (e.g.<5%) compared to their litter mate controls (TTP+/+). Results showed that severe α-T deficiency result in a blunted lung expression of IL-5 mRNA and IL-5 protein and plasma IgE levels compared with TTP+/+ mice following immune sensitization and rechallenge, although lung lavage eosinophil levels were comparable in both genomic strains. It is concluded that the initial stimulation of immune responses by the TTP−/− mice were generally blunted compared to the TTP+/+ mice, thus diminishing some aspects of subsequent allergic inflammatory processes.

Regulation of the α-tocopherol transfer protein in mice : Lack of response to dietary vitamin E or oxidative stress

The α-tocopherol transfer protein (TTP) plays an important role in the regulation of plasma α-tocopherol concentrations. We hypothesized that hepatic TTP levels would be modulated by dietary vitamin E supplementation and/or by oxidative stress. Mice were fed either a High E (1150 mg RRR-α-tocopheryl acetate/kg diet) or a Low E (11.5 mg/kg diet) diet for 2 wk. High E increased plasma and liver α-tocopherol concentrations approximately 8- and 40-fold, respectively, compared with Low E-fed mice, whereas hepatic TTP increased approximately 20%. Hepatic TTP concentrations were unaffected by fasting (24 h) in mice fed either diet. To induce oxidative stress, chow-fed mice were exposed for 3 d to environmental tobacco smoke (ETS) for 6 h/d (total suspended particulate, 57.4±1.8 mg/m3). ETS exposure, while resulting in pulmonary and systemic oxidative stress, had no effect on hepatic α-tocopherol concentrations or hepatic TTP. Overall, changes in hepatic TTP concentrations were minimal in response to dietary vitamin E levels or ETS-related oxidative stress. Thus, hepatic TTP concentrations may be at sufficient levels such that they are unaffected by either modulations of dietary vitamin E or by the conditions of environmentally related oxidative stress used in the present studies.