Abstract-Intake of flavonoids is associated with a reduced cardiovascular risk. Oxidation of LDL is a major step in atherogenesis, and antioxidants may protect LDL from oxidation. Because tea is an important source of flavonoids, which are strong antioxidants, we have assessed in a randomized, placebo-controlled study the effect of consumption of black and green tea and of intake of isolated green tea polyphenols on LDL oxidation ex vivo and on plasma levels of antioxidants and lipids. Healthy male and female smokers (aged 34Ϯ12 years, 13 to 16 per group) consumed during a 4-week period 6 cups (900 mL) of black or green tea or water per day, or they received as a supplement 3.6 grams of green tea polyphenols per day (equivalent to the consumption of 18 cups of green tea per day). Consumption of black or green tea had no effect on plasma cholesterol and triglycerides, HDL and LDL cholesterol, plasma vitamins C and E, ␤-carotene, and uric acid. No differences were found in parameters of LDL oxidation. Intake of green tea polyphenols decreased plasma vitamin E significantly in that group compared with the control group (Ϫ11% Pϭ.016) but had no effect on LDL oxidation ex vivo. We conclude that consumption of black or green tea (6 cups per day) has no effect on plasma lipids and no sparing effect on plasma antioxidant vitamins and that intake of a high dose of isolated green tea polyphenols decreases plasma vitamin E. Although tea polyphenols had a potent antioxidant activity on LDL oxidation in vitro, no effect was found on LDL oxidation ex vivo after consumption of green or black tea or intake of a green tea polyphenol isolate. (Arterioscler Thromb Vasc Biol. 1998;18:833-841.)

There is accumulating evidence that oxidative modification of LDL is an important step in the process of atherogenesis and that antioxidants may protect LDL from oxidation. We and others have previously shown that ingestion of pharmacological doses of the antioxidant D,L-alpha-tocopherol (vitamin E), far above the recommended daily intake (ie, 12 to 15 IU/d for adults), increases the oxidation resistance of LDL. In this study, we ascertained the minimal supplementary dose of vitamin E necessary to protect LDL against oxidation in vitro. Twenty healthy volunteers (10 men and 10 women, aged 21 to 31 years) ingested consecutively 25, 50, 100, 200, 400, and 800 IU/d, D,L-alpha-tocopherol acetate during six 2-week periods. No changes were observed in LDL triglyceride content, fatty acid composition of LDL, or LDL size during the intervention. Concentrations of alpha-tocopherol in plasma and LDL were both 1.2 times the baseline values after the first period (25 IU/d) and 2.6 and 2.2 times, respectively, after the last period (800 IU/d). There was a linear increase in LDL alpha-tocopherol levels up to an intake of 800 IU/d (r = .79, P < .0001) and a good correlation between alpha-tocopherol in plasma and LDL (r = .66, P < .0001). Simultaneously, the resistance of LDL to oxidation was elevated dose-dependently (+28% after the last period) and differed significantly from the baseline resistance time even after ingestion of only 25 IU/d.(ABSTRACT TRUNCATED AT 250 WORDS)

Background:Non-alcoholic fatty liver disease (NAFLD) is strongly associated with abdominal obesity. Growing evidence suggests that inflammation in specific depots of white adipose tissue (WAT) has a key role in NAFLD progression, but experimental evidence for a causal role of WAT is lacking.Methods:A time-course study in C57BL/6J mice was performed to establish which WAT depot is most susceptible to develop inflammation during high-fat diet (HFD)-induced obesity. Crown-like structures (CLS) were quantified in epididymal (eWAT), mesenteric (mWAT) and inguinal/subcutaneous (iWAT) WAT. The contribution of inflamed WAT to NAFLD progression was investigated by surgical removal of a selected WAT depot and compared with sham surgery. Plasma markers were analyzed by enzyme-linked immunosorbent assay (cytokines/adipokines) and lipidomics (lipids).Results:In eWAT, CLS were formed already after 12 weeks of HFD, which coincided with maximal adipocyte size and fat depot mass, and preceded establishment of non-alcoholic steatohepatitis (NASH). By contrast, the number of CLS were low in mWAT and iWAT. Removal of inflamed eWAT after 12 weeks (eWATx group), followed by another 12 weeks of HFD feeding, resulted in significantly reduced NASH in eWATx. Inflammatory cell aggregates (−40% P<0.05) and inflammatory genes (e.g., TNFα, −37% P<0.05) were attenuated in livers of eWATx mice, whereas steatosis was not affected. Concomitantly, plasma concentrations of circulating proinflammatory mediators, viz. leptin and specific saturated and monounsaturated fatty acids, were also reduced in the eWATx group.Conclusions:Intervention in NAFLD progression by removal of inflamed eWAT attenuates the development of NASH and reduces plasma levels of specific inflammatory mediators (cytokines and lipids). These data support the hypothesis that eWAT is causally involved in the pathogenesis of NASH.

HFD induces detrimental effects in mid- and late-adult mice, which can be attenuated by butyrate intervention. These findings are consistent with reported associations between midlife obesity and cognitive impairment and dementia in humans. We suggest that butyrate may have potential in prevention and treatment of midlife obesity.

Treatment with avasimibe potently lowered plasma cholesterol levels in ApoE*3-Leiden mice and considerably reduced atherosclerotic lesion area in addition to its cholesterol-lowering effect. Because monocyte adherence to the endothelium and lesion severity were also reduced by avasimibe, treatment with avasimibe may result in higher plaque stability and therefore a reduced risk of plaque rupture.