Thymoquinone, a major constituent in Nigella sativa seeds, is a potential preventative and treatment option for atherosclerosis.

Atherosclerosis is a widespread and progressive chronic arterial disease that remains the leading cause of mortality and morbidity worldwide. It is generally accepted that atherosclerosis is a multifactorial disease characterized by dyslipidemia and inflammation in the vessel walls. Nonpharmacological interventions to treat chronic diseases like atherosclerosis have gained considerable attention in recent years. Thymoquinone (TQ), the major bioactive constituent of Nigella sativa seeds, presents one such example of a natural therapeutic agent that has captured the attention of many researchers due to its wide array of medicinal properties, including its potent anti-atherosclerotic effects. Various in vitro and in vivo studies support the potential of TQ in ameliorating hyperlipidemia, hypercholesterolemia, oxidative stress, and inflammation, all of which are key hallmarks of atherosclerosis. However, to date, no review has been conducted to substantiate the role of TQ in preventing and/or treating atherosclerosis. This comprehensive review aims to examine recent in vitro and in vivo experimental findings reported on the potential anti-atherosclerotic effects of TQ. The roles of TQ in combatting hyperlipidemia, oxidative stress, and inflammation in atherosclerosis are highlighted. We also shed light on the role of TQ in preventing foam cell formation by decreasing low-density lipoprotein (LDL) availability and oxidation. Moreover, recent findings on the protective role of TQ on early markers of atherosclerosis, including homocysteinemia and endothelial dysfunction, are also underscored. Experimental evidence suggests that TQ can potentially be employed as a natural therapeutic agent with minimal side effects against the development and/or progression of atherosclerosis and its associated complications.

Cordycepin attenuates high-fat diet-induced non-alcoholic fatty liver disease via down-regulation of lipid metabolism and inflammatory responses.

Cordycepin (CRD), an adenosine analog derived from traditional Chinese medicine, is an active component in Cordyceps militaris. It has been shown to have many protective effects during liver injury and ameliorate liver disease progression, but little is known about its effect on non-alcoholic fatty liver disease (NAFLD). This study aims to explore the effects of CRD on obesity-induced NAFLD. In this experiment, C57BL/6 J mice were randomly assigned into normal control group (NC), high fat diet group (HFD) and HFD + CRD group for 8 weeks. The body weights were recorded weekly, at the end of the experiments, the liver and serum samples were collected. We found that CRD administration reduced body weight and decreased the weight of adipose and liver, and CRD relieved liver injure through diminishing of histopathological changes and decreasing serum levels of AST, ALT, TG, TC, LDL-C and increased the level of HDL-C. Furthermore, treatment with CRD significantly alleviated expression of inflammatory factors (TNF-α, IL-6 and Il-1ß) and macrophage markers (MCP1, MIP2, mKC and VCAM1). On the other hand, compared with HFD group, the CRD treated group markedly down-regulated relative proteins of lipid anabolism (SREBP1-c, ACC, SCD-1, LXRα and CD36) and up-regulated relative proteins of ß-oxidation (p-AMPK, AMPK, CPT-1 and PPARα). In summary, our results suggest that CRD can be a potential therapeutic agent in the prevention and treatment of NAFLD, which may be closely related to its effect on lipid metabolism and inflammatory responses.

Raspberry anthocyanin consumption prevents diet-induced obesity by alleviating oxidative stress and modulating hepatic lipid metabolism.

Evidence indicates that raspberries have beneficial effects on chronic diseases. The objective of this study was to examine the beneficial effects of raspberry anthocyanin (RA) on high fat diet-induced obesity and investigate the underlying molecular mechanism. C57BL/6 mice were administered a low-fat diet, high-fat diet, and high-fat diet supplemented with RA at a dose of 200 mg kg-1 of food for 12 weeks. It was found that RA reduced the body weight gain by 63.7%. Furthermore, RA significantly elevated serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities and fecal butyric acid level, remarkably reduced the serum and hepatic lipid profiles, and markedly down-regulated the expression of the tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and nuclear factor κB (NF-κB) genes. Metabolomics analysis conducted using gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) indicated that RA administration promoted the recovery of metabolites involved in glycerophospholipid metabolism, insulin signaling pathway, and glutathione metabolism in the livers of obese mice. These findings suggest that RA may ameliorate diet-induced obesity by alleviating oxidative stress and modulating lipid metabolism.

(-)-Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high-fat diet.

SCOPE: (-)-Epicatechin (EC) is a natural flavanol monomer found in cocoa, green tea, and a variety of other plant foods. In this study, effects of EC on blood lipids and hepatic steatosis, and the underlying mechanisms were investigated. METHODS AND RESULTS: A hyperlipidemic rat model was induced by high-fat, high-cholesterol diet. EC was then administrated to the animals by gavage at doses of 10, 20, 40 mg/kg body weight (BW) for 12 weeks. Simvastatin was included as a positive control. The results showed that EC significantly reduced total cholesterol, LDL cholesterol and triglyceride, alleviated liver fat accumulation, while increased HDL cholesterol, in hyperlipidemic rats. EC also reduced lipid peroxidation, inhibited the pro-inflammatory cytokines, and lowered serum AST and ALT. The potential molecular mechanisms of EC underlying these effects were proposed to be associated to regulating Insig-1-SREBP-SCAP pathway, and other lipid metabolic related genes including LXR-α, FAS, and SIRT1. CONCLUSION: EC effectively improved blood lipid profile and protected liver from accumulating excessive fat in hyperlipidemic rats. The results shed a light on the potential role of EC as a promising natural product in preventing hyperlipidemia and nonalcoholic fatty liver disease.

Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis.

Citrus flavonoids are polyphenolic compounds with significant biological properties. This review summarizes recent advances in understanding the ability of citrus flavonoids to modulate lipid metabolism, other metabolic parameters related to the metabolic syndrome, and atherosclerosis. Citrus flavonoids, including naringenin, hesperitin, nobiletin, and tangeretin, have emerged as potential therapeutics for the treatment of metabolic dysregulation. Epidemiological studies reveal an association between the intake of citrus flavonoid-containing foods and a decreased incidence of cardiovascular disease. Studies in cell culture and animal models, as well as a limited number of clinical studies, reveal the lipid-lowering, insulin-sensitizing, antihypertensive, and anti-inflammatory properties of citrus flavonoids. In animal models, supplementation of rodent diets with citrus flavonoids prevents hepatic steatosis, dyslipidemia, and insulin resistance primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose, kidney, and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established, although several potential targets have been identified. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters as well as through direct impact on the vessel wall. Recent studies support a role for citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity, and atherosclerosis. Larger human studies examining dose, bioavailability, efficacy, and safety are required to promote the development of these promising therapeutic agents.

Decaffeinated green tea extract rich in epigallocatechin-3-gallate improves insulin resistance and metabolic profiles in normolipidic diet--but not high-fat diet-fed mice.

Supplementation with epigallocatechin-3-gallate (EGCG), which restores metabolic profiles, has been proposed as an option for preventing and treating obesity. We investigated whether decaffeinated green tea extract rich in EGCG, attenuates high-fat diet (HFD)-induced metabolic alterations in Swiss mice. The mice were maintained on either a control diet (CD) or HFD for 8 weeks and supplemented with either a placebo or EGCG (50mg/kg/day). Body weight, serum lipid profiles, cytokine protein expression, and content in epididymal (EPI) and retroperitoneal (RET) adipose tissues, and adipocyte area were measured. The body weights of HFD + placebo-fed mice were increased compared with those of HFD + EGCG-fed mice (28 and 21%, respectively), whereas the body weights of CD + EGCG-fed mice were decreased 16% compared with those of the CD + placebo group. Serum triglyceride levels were decreased 32% in the CD + EGCG group compared with the CD + placebo group. Compared with the CD + placebo group, increased phosphorylation of AMPK and hormone-sensitive lipase in EPI and RET, respectively, was found in the CD + EGCG group. Increased acetyl-CoA carboxylase phosphorylation was observed in both adipose tissues. In addition, TNF-α and IL-10 levels in EPI and adiponectin levels were higher in the CD + EGCG group than in the CD + placebo group. TNF-α levels were lower in the HFD + EGCG group than in the HFD + placebo group. Furthermore, the CD + EGCG group exhibited a lower adipocyte area than the CD + placebo group. These indicate that the effects of decaffeinated green tea extract on body mass may be related to the crosstalk between lipolytic and inflammatory pathways in normolipidic diet-fed mice but not in HFD-fed mice.

Fish Oil Contaminated with Persistent Organic Pollutants Reduces Antioxidant Capacity and Induces Oxidative Stress without Affecting Its Capacity to Lower Lipid Concentrations and Systemic Inflammation in Rats.

BACKGROUND: Numerous studies have investigated the benefits of fish, fish oil, and ω-3 (n-3) polyunsaturated fatty acids against cardiovascular diseases. However, concern surrounding contamination with persistent organic pollutants (POPs) prompts caution in the recommendation to consume fish and fish oil. OBJECTIVE: The present study compared the effects of fish oil contaminated with polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs) on serum lipid profiles, inflammation, and oxidative stress. METHODS: Twenty eight-day-old male Sprague-Dawley rats (n = 30) consumed diets of unmodified fish oil (FO) consisting of 15% fat by weight, persistent organic pollutant-contaminated fish oil (POP FO) (PCBs at 2.40 µg/g; OCs at 3.80 µg/g FO), or corn oil (control; CO) for 9 wk. Lipid profiles and C-reactive protein concentrations were assessed. Hepatic gene expression related to lipid metabolism was determined by real time quantitative polymerase chain reaction analysis. RESULTS: After 9 wk of feeding, accumulation of PCBs and OCs in the fat tissue of the POP FO group compared with the other 2 groups was confirmed (P < 0.01). Both fish oil groups showed greater HDL cholesterol (FO 53 ± 5.3 and POP FO 55 ± 7.7 vs. CO 34 ± 2.3 mg/dL), but lower triglycerides (24 ± 2.8 and 22 ± 3.0 vs. 43 ± 5.6 mg/dL), LDL cholesterol (38 ± 14 and 34 ± 9.2 vs. 67 ± 4.4 mg/dL), and C-reactive protein (113 ± 20 and 120 ± 26 vs. 189 ± 22 µg/dL) compared with the CO group (P < 0.05). Gene expression of fatty acid synthase in both fish oil groups was also less than in the CO group (P < 0.05). However, the POP FO group showed greater lipid peroxidation (5.1 ± 0.7 vs. 2.9 ± 0.9 and 2.6 ± 0.6 µM) and less antioxidant capacity (0.08 ± 0.06 vs. 0.5 ± 0.1 and 0.4 ± 0.1 mM) than the CO and FO groups (P < 0.05). CONCLUSIONS: These findings indicate that, despite exhibiting benefits on serum lipid concentrations and inflammation, contamination with PCBs and OCs showed significant negative effects on oxidative stress and antioxidant capacity in rats. Future studies should investigate the effects of different contaminant doses and the possibility of a dose-dependent response, a lengthened feeding time, and interactions between contaminant mixtures and oils of varying composition to advise on dietary consumption of fish and fish oil.

Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile.

Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the "biosynthesis of unsaturated fatty acids" pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment.

[Effect of electroacupuncture stimulation of "Fenglong" (ST 40) on expression of inflammatory cytokines of celiac macrophages in hyperlipidemia rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40) on celiac inflammatory factors in rats with hyperlipemia (HLP), so as to reveal its mechanism underlying improvement of HLP. METHODS: A total of 40 SD rats were randomized into normal control, high fat forage, high fat + common forage, high fat + EA, and high fat + common forage+ EA groups, with 8 rats in each group. The HLP model was established by feeding the animals with high fat forage for 28 days. EA (2 mA, 2 Hz/100 Hz) was applied to bilateral ST 40 for 30 min, once daily for 28 days. Contents of plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were detected by using an automatic biochemistry analyzer. Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein 1 (MCP-1), and interleukin-1 gamma (IL-1gamma) in macrophages of the abdominal cavity were detected using flow cytometry (FCM). RESULTS: Compared with the normal control group, the contents of plasma TC and LDL-C, and celiac macrophages' MCP-1, ICAM-1 and IL-1gamma contents were significantly increased in the high fat forage group and high fat + common forage group (P < 0.01). In comparison with the high fat forage group, contents of plasma TC and LDL-C, and macrophages' MCP-1, ICAM-1 and IL-1gamma were considerably down-regulated in the high fat + EA group (P < 0.01). Similarly, the levels of plasma TC and LDL-C, and macrophages' MCP-1, ICAM-1 and IL-1gamma were obviously lower in the high fat+ common forage+ EA group than in the high fat + common forage group (P < 0.01). No significant differences were found in plasma TG and HDL-C levels among the five groups (P > 0.05). CONCLUSION: EA stimulation of "Fenglong" (ST 40) has a role in down-regulating contents of plasma TC and LDL-C and celiac macrophages' MCP-1, ICAM-1 and IL-1gamma in the abdominal cavity in hyperlipemia rats, which may contribute to its effect in improving hyperlipemia.

Short-term intensive atorvastatin therapy improves endothelial function partly via attenuating perivascular adipose tissue inflammation through 5-lipoxygenase pathway in hyperlipidemic rabbits.

BACKGROUND: Atherosclerosis is a kind of disease with multiple risk factors, of which hyperlipidemia is a major classical risk factor resulting in its pathogenesis and development. The aim of this study was to determine the effects of short-term intensive atorvastatin (IA) therapy on vascular endothelial function and explore the possible mechanisms that may help to explain the clinical benefits from short-term intensive statin therapy. METHODS: After exposure to high-fat diet (HFD) for 8 weeks, the animals were, respectively, treated with IA or low-dose atorvastatin (LA) for 5 days. Blood lipids, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), endothelin-1 (ET-1), and endothelium-dependent vasorelaxation function were, respectively, measured. mRNA and protein expression of CRP, TNF-α, IL-6, macrophage chemoattractant protein-1 (MCP-1), and 5-lipoxygenase (5-LO) were also evaluated in pericarotid adipose tissue (PCAT) and cultured adipocytes. RESULTS: HFD increased serum inflammatory factor levels; induced significant hyperlipidemia and endothelial dysfunction, including imbalance between NO and ET-1; enhanced inflammatory factors and 5-LO expression; and promoted macrophage infiltration into adipose tissue. Five-day IA therapy could significantly decrease serum inflammatory factor levels and their expression in PCAT; restore the balance between NO and ET-1; and improve endothelial function and macrophage infiltration without significant changes in blood lipids. However, all of the above were not observed in LA therapy. In vitro experiment found that lipopolysaccharide (LPS) enhanced the expression of inflammatory factors and 5-LO in cultured adipocytes, which could be attenuated by short-time (6 hours) treatment of high-dose (5 µmol/L) but not low-dose (0.5 µmol/L) atorvastatin. In addition, inhibiting 5-LO by Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC, a potent and direct 5-LO inhibitor) could significantly downregulate the above-mentioned gene expression in LPS-treated adipocytes. CONCLUSION: Short-term IA therapy could significantly ameliorate endothelial dysfunction induced by HFD, which may be partly due to attenuating inflammation of PCAT through inhibiting 5-LO pathway.

[Effects of mild moxibustion on imbalance of Th1/Th2 in rabbits with atherosclerosis and its regulating rules].

OBJECTIVE: To observe effects of mild moxibustion and lovastatin on immunologic function in rabbits with chronic hyperlipidaemia and atherosclerosis (AS) to initially explain regulating rules of mild moxibustion on immunologic function. METHODS: Among thirty-two Japanese male big-ear rabbits, 8 rabbits were randomly selec ted as a blank group, the rest 24 rabbits were fed with method of endothelial injury and high-fat diet to establish AS model. The blank group was raised with normal diet and free water. After ten weeks of model establishment, the rest 24 rabbits were randomly divided into a model group, a moxibustion group and a medicine group, eight rabbits in each one. Moxibustion was applied at "Shenque" (CV 8) and "Zusanli" (ST 36) for 10 min per acupoint per day in the moxibustion group, while intragastric administration of 3.6 mg/kg lovastatin capsule was applied in the medicine group. After treatment, serum was acquired. Spectrophotometry method was adapted to measure cholesterol (TC) and high-density lipoprotein (HDL-C) and evaluated atherosclerosis index (AI), while enzyme-linked immunosorbent assay method was used to measure interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). RESULTS: (1) The serum TC and HDL-C in the model group were significantly higher than those in the blank group, moxibustion group and medicine group (all P < 0.01). The mean value of AI was 1.683 +/- 0.486 in the moxibustion group, which was obviously lower than 20.301 +/- 4.022 in the model group (P < 0.01). (2) The ratio of Th1/Th2 was 0.569 +/- 0.143 in the moxibustion group and 0.445 +/- 0.079 in the medicine group, which were significantly lower than 0.917 +/- 0.255 in the model group (both P < 0.01), but there was no statistically significant difference between the moxibustion group and the medicine group (P > 0.05). CONCLUSION: The moxibustion for AS could reduce atherosclerosis index, influence drift and bias of helper T cell and regulate balance between humoral immunity and cellular immunity. As a result, status of relative balance of immunity is acquired, which could slow down the development of atherosclerosis and process of thrombus burst.

Postnatal dietary omega-3 fatty acid supplementation rescues glucocorticoid-programmed adiposity, hypertension, and hyperlipidemia in male rat offspring raised on a high-fat diet.

Fetal glucocorticoid excess programs several adverse outcomes in adult offspring, many of which can be prevented by postnatal, dietary omega-3 (n-3) fatty acids. Here we tested 2 separate hypotheses: 1) a postnatal high-fat diet exacerbates the glucocorticoid-programmed phenotype; and 2) postnatal, dietary n-3 fatty acids rescue programmed outcomes, even in the presence of a high-fat diet challenge. Pregnant Wistar rat dams were either untreated or administered dexamethasone acetate (Dex; 0.5 µg/mL drinking water) from day 13 of pregnancy. Offspring were cross-fostered to untreated mothers and males were weaned onto a standard (Std), high-fat, low n-3 (HF), or high-fat, high n-3 (HFHn-3) diet. Prenatal Dex reduced birth weight (26%) and delayed puberty onset by 1.2 days, irrespective of postnatal diet. Prenatal Dex programmed increased blood pressure in adult offspring, an effect worsened by the postnatal HF diet. Supplementation with high n-3 fatty acids, however, prevented both the Dex and HF-induced increases in blood pressure. Prenatal Dex also programmed increased adiposity, plasma cholesterol, and plasma triglyceride levels at 6 months of age, particularly in those offspring raised on the HF diet. But again, each of these adverse outcomes was rescued by supplementation of the HF diet with n-3 fatty acids. In conclusion, the capacity of n-3 fatty acids to overcome adverse programming outcomes remains evident, even in the presence of a HF diet challenge.

[Effect of electroacupuncture of "Fenglong" (ST 40) on levels of blood lipid and macrophage TNF-alpha and IL-6 in hyperlipidemic rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40) on blood lipid contents and inflammatory factor levels in hyperlipemia rats so as to elucidate its mechanism underlying improvement of hyperlipemia. METHODS: Fifty male SD rats were randomized into 5 groups: normal, model, diet -control, EA intervention (EA), diet-control + EA groups, with 10 rats in each group. Hyperlipemia model was established by feeding the animals with high-fat diet for 30 days. After modeling, rats in the diet-control group were fed with routine fodder. EA was applied to bilateral "Fenglong" (ST 40) for 30 min, once daily for 30 days. Following intraperitoneal injection of 1640 culture fluid, the peritoneal fluid was collected and centrifuged for extracting macrophages. Flow cytometry (FCM) was employed to determine the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) after adding fluoresce-labeled antibodies. RESULTS: The contents of serum TC and LDL-C were remarkably higher and HDL-C level was significantly lower in the model group than in the normal group (P < 0.01). After EA intervention, serum TC and LDL-C showed an apparent decrease (P < 0.01). Compared with the normal group, percentages of CD11 b, TNF-alpha and IL-6 were significantly increased in the model group (P < 0.01), while in comparison with the model group, percentages of CD11 b in both EA and diet-control + EA groups, TNF-alpha and IL-6 percentages of macrophages in the diet-control, EA and diet-control + EA groups were notably decreased (P < 0.05, P < 0.01). The effects of the diet-control + EA group were considerably superior to those of the diet-control group in lowering CD11 b, TNF-alpha and IL-6 percentages (P < 0.05, P < 0.01). No significant differences were found between the diet-control and EA groups in the aforementioned indexes (P > 0.05). CD11 b level indicates changes of macrophage level due to its specific marker character. CONCLUSION: EA stimulation of "Fenglong" (ST 40) is effective in lowering serum TC, LDL-C, and macrophage TNF-alpha and IL-6 levels in hyperlipemia rats.

[Protection of huanglian jiedu decoction on systemic and vascular immune responses of high fat induced apoE(-/-) mice].

OBJECTIVE: To observe the effect of Huanglian Jiedu IJecoction (HJU) on systemic and vascular immune responses of high fat diet fed apoE deficient (apoE(-/-)) mice. METHODS: Eight wild type C57BL6 mice were recruited as the wild type common food group. Totally 24 apoE(-/-) mice were randomly divided into the ApoE'common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/-) hyperlipidemia plus HJD group, 8 in each group. In the present study, the common food mice and high fat fed mice were fed with a chow diet or a high cholesterol diet for 4 weeks. HJD was given to mice in the ApoE(-/-) hyperlipidemia plus HJD group at the daily dose of 5 g/kg by gastrogavage, while equal volume of pure water was given to mice in the rest groups by gastrogavage. Four weeks later, the plasma levels of blood lipids, the ratio of peripheral blood mononuclear cells, and expressions of Toll-like receptor 4 (TLR-4) and CD36 on the monocytes were detected. The pathological changes and expressions of cytokines in local aorta were detected. The plasma cytokine levels in response to lipopolysaccharide (LPS) were analyzed. Results (1) Compared with the wild type common food group, TO, TG, and LDL-O significantly increased in the ApoE(-/-) common food group (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, TC and LDL-C significantly increased in the hyperlipidemia group (P < 0. 05). There was no statistical difference in each index between the ApoE(-/-) hyperlipidemia group and the ApoE(-/-) hyperlipidemia plus HJD group (P > 0.05). (2) Compared with the wild type common food group, no obvious change of the ratio of peripheral blood mononuclear cells happened, the TLR4 expression level significantly increased in the ApoE'common food group (P < 0. 05). Compared with the ApoE common food group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly increased in the ApoE' hyperlipidemia group (P < 0.05). Compared with the ApoE(-/-) hyperlipidemia group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly decreased. Besides, the CD36 expression level also significantly decreased (P<0.05). (3) After stimulated by LPS for 3 h, compared with the wild type common food group, plasma TNF-ct and IL-b expressions significantly increased in the ApoE(-/-) common food group (P < 0.05). Compared with the ApoE(-/-) common food group, plasma expressions of IL-12, TNF-alpha, MCP-1, and IL-10 increased, but with no statistical difference in the ApoE(-/-) hyperlipidemia group (P > 0.05). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, the MCP-1 expression was significantly down-regulated, while the IL-10 expression significantly increased, showing statistical difference (P < 0.05). Compared with the wild type common food group, mRNA expression levels of IFN-gamma, MCP-1 , TNF-alpha, IL-10, and IL-1beta significantly increased (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, not only mRNA expression levels of IFN-gamma, MCP-1, TNF-alpha, and IL-1beta, further significantly increased, but also IL-12, IL-10, and TGF-beta significantly increased (P < 0. 05, P < 0. 01). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, mRNA expression levels of MCP-1, TNF-alpha, IL-1beta, and IL-12 significantly decreased in the ApoE(-/-) hyperlipidemia plus HJD group (P < 0.05, P < 0.01). CONCLUSIONS: High fat diet induced systemic reaction and inflammatory reactions of local vessels. The local inflammatory response of vessels exceeded systemic inflammatory response. Intervention of HJD could attenuate inflammatory response, especially in local arteries. Meanwhile, it enhanced systemic anti-inflammatory reactions.

[Middle-aged female presenting with headache, blurred vision and skin rash]. / Ei kvinne i 50-åra med hovudverk, uklart syn og utslett.

BACKGROUND: Autoimmune hyperlipidemia (AIH) is a rare cause of secondary hyperlipidemia. A few cases of AIH have been reported in multiple myeloma. MATERIAL AND METHODS: A female in her fifties was referred to the outpatient clinic presenting with headache, blurred vision and skin rash. Physical examination with subsequent laboratory and histological examinations revealed severe hyperlipidemia secondary to secretory multiple myeloma with monoclonal IgG kappa protein and erythrocytosis secondary to a erythropoietin secreting adenoma in the liver. RESULTS AND INTERPRETATION: Treatment for multiple myeloma (induction treatment and autologous hematological stem cell transplantation) gained partial remission and was associated with normalization of serum lipids. There was no need for further medical treatment of the hyperlipidemia. Three years after the initial treatment, serum concentrations of triglycerides and total cholesterol increased in parallel with monoclonal IgG kappa protein. Total cholesterol and triglycerides decreased and remained within the reference ranges after retreatment with a second autologous stem cell transplantation. Surgical removal of the hepatic adenoma caused normalisation of the erythropoietin concentration and resolution of the erythrocytosis. The present case reports two rare complications (AIH and erythrocytosis) to multiple myeloma and hepatic adenoma, with regression of complaints and normalisation of laboratory tests after adequate treatment of underlying diseases.

Arachidonic acid/docosahexaenoic acid-supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3Leiden mice.

SCOPE: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic mice, a humanized model for hyperlipidemia and mild obesity. METHODS AND RESULTS: Four-week-old male ApoE*3Leiden mice were fed chow diet with or without a mixture of ARA (0.129 wt%) and DHA (0.088 wt%) or Omacor (0.30 wt% EPA, 0.25 wt% DHA). At age 12 weeks, mice were fed high-fat/high-carbohydrate (HFHC) diet without above supplements until age 20 weeks. Control mice received chow diet throughout the study. Mice receiving ARA/DHA gained less body weight compared to control and this effect was sustained when fed HFHC. Omacor had no significant effect on body weight gain. Plasma cholesterol and triglycerides were significantly lowered by both supplementations. At 20 weeks, epididymal fat mass was less in ARA/DHA-supplemented mice, while Omacor had no significant effect on fat mass. Both ARA/DHA and Omacor reduced inguinal adipocyte cell size; only ARA/DHA significantly reduced epididymal macrophage infiltration. CONCLUSION: This study shows that early life ARA/DHA, but not Omacor supplementation improves body weight gain later in life. ARA/DHA and to a lesser extent Omacor both improved adipose tissue quality.

Severe hyperhomocysteinemia promotes bone marrow-derived and resident inflammatory monocyte differentiation and atherosclerosis in LDLr/CBS-deficient mice.

RATIONALE: Hyperhomocysteinemia (HHcy) accelerates atherosclerosis and increases inflammatory monocytes (MC) in peripheral tissues. However, its causative role in atherosclerosis is not well established and its effect on vascular inflammation has not been studied. The underlying mechanism is unknown. OBJECTIVE: This study examined the causative role of HHcy in atherogenesis and its effect on inflammatory MC differentiation. METHODS AND RESULTS: We generated a novel HHcy and hyperlipidemia mouse model, in which cystathionine ß-synthase (CBS) and low-density lipoprotein receptor (LDLr) genes were deficient (Ldlr(-/-) Cbs(-/+)). Severe HHcy (plasma homocysteine (Hcy)=275 µmol/L) was induced by a high methionine diet containing sufficient basal levels of B vitamins. Plasma Hcy levels were lowered to 46 µmol/L from 244 µmol/L by vitamin supplementation, which elevated plasma folate levels. Bone marrow (BM)-derived cells were traced by the transplantation of BM cells from enhanced green fluorescent protein (EGFP) transgenic mice after sublethal irradiation of the recipient. HHcy accelerated atherosclerosis and promoted Ly6C(high) inflammatory MC differentiation of both BM and tissue origins in the aortas and peripheral tissues. It also elevated plasma levels of TNF-α, IL-6, and MCP-1; increased vessel wall MC accumulation; and increased macrophage maturation. Hcy-lowering therapy reversed HHcy-induced lesion formation, plasma cytokine increase, and blood and vessel inflammatory MC (Ly6C(high+middle)) accumulation. Plasma Hcy levels were positively correlated with plasma levels of proinflammatory cytokines. In primary mouse splenocytes, L-Hcy promoted rIFNγ-induced inflammatory MC differentiation, as well as increased TNF-α, IL-6, and superoxide anion production in inflammatory MC subsets. Antioxidants and folic acid reversed L-Hcy-induced inflammatory MC differentiation and oxidative stress in inflammatory MC subsets. CONCLUSIONS: HHcy causes vessel wall inflammatory MC differentiation and macrophage maturation of both BM and tissue origins, leading to atherosclerosis via an oxidative stress-related mechanism.

Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men.

BACKGROUND: Inflammation is crucial in all stages of atherosclerosis, and few studies have investigated the effect of dietary fat on markers of inflammation related to this disease during the postprandial period. OBJECTIVE: To evaluate the chronic effects of dietary fat on the postprandial expression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) in healthy subjects. DESIGN: 20 healthy men followed three different diets for 4 weeks each, according to a randomized crossover design: Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); CHO-rich and n-3 diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After 12-h fast, volunteers were given a breakfast with a fat composition similar to that consumed in each of the diets-butter breakfast: 35% SFA; olive oil breakfast: 36% MUFA; walnut breakfast: 16% PUFA, 4% alpha-linolenic acid (LNA). RESULTS: The butter breakfast induced a higher increase in tumor necrosis factor (TNF)-alpha messenger RNA (mRNA) expression than the olive oil or walnut breakfasts (P=0.014) in PBMCs. Moreover, we found a higher postprandial response in the mRNA of interleukin (IL)-6 with the intake of butter and olive oil breakfasts than with the walnut breakfast (P=0.025) in these cells. However, the effects of the three fatty breakfasts on the plasma concentrations of these proinflammatory parameters showed no significant differences (P=N.S.). CONCLUSION: Consumption of a butter-enriched meal elicits greater postprandial expression of proinflammatory cytokine mRNA in PBMCs, compared to the olive oil and walnut breakfasts.

Effect of the extract of the tamarind (Tamarindus indica) fruit on the complement system: studies in vitro and in hamsters submitted to a cholesterol-enriched diet.

This work evaluated a crude hydroalcoholic extract (ExT) from the pulp of the tamarind (Tamarindus indica) fruit as a source of compounds active on the complement system (CS) in vitro. ExT, previously characterized by other authors, had time and concentration dependent effects on the lytic activity of the CS. The activity of 0.8 mg/mL of the extract on the classical/lectin pathways (CP/LP) increased after 30 min of pre-incubation, while that of the alternative pathway (AP) decreased after 15 min at 1mg/mL. Since the CS is a mediator of inflammation, studies were also made in vivo, taking advantage of a model of hypercholesterolemia in hamsters to investigate the role of CS in the phase preceding the inflammatory process of atherosclerosis. Hamsters submitted to a diet rich in cholesterol showed increased lytic activity of the CP/LP and AP after 45 days. The activity levels of C2 and factor B components on respectively, classical/lectin and alternative pathways of the CS also increased. Early events cooperating to trigger the process of atherosclerotic lesions are not completely understood, and these alterations of complement may participate in these events. When treatment with a diet rich in cholesterol was associated to the furnishing of ExT, evaluation of complement components and complement lytic activity showed values similar to those of the controls, showing that treatment with ExT blocked the increase of complement activity caused by the cholesterol-rich diet. By itself, ExT had no effect on the complement system in vivo. ExT activity on the CS may be of interest for therapy and research purposes.