Immunomodulation of IL-33 and IL-37 with Vitamin D in the Neointima of Coronary Artery: A Comparative Study between Balloon Angioplasty and Stent in Hyperlipidemic Microswine.

Inflammation is a major contributor to the development and progression of atherosclerosis. Interleukin (IL)-33 and IL-37, members of the IL-1 family, modulate inflammation, with IL-33 having a pro-inflammatory effect and IL-37 having anti-inflammatory properties. IL-37 is constitutively expressed at low levels but upregulated in inflammatory contexts. The aim of this study was to evaluate the effect of vitamin D on the expression of IL-33, IL-37, macrophages, and caspase-1 in the neointimal tissue of coronary artery in Yucatan microswine with vitamin D deficient, sufficient, and supplemented status. The intimal injury was induced by balloon angioplasty and stenting in the coronary artery, and tissues were harvested after 6 months. The expression of various proteins of interest was evaluated by immunostaining. Increased expression of IL-33 and IL-37 in the neointimal tissue of the vitamin D deficient, as compared to the sufficient and supplemented microswine, as revealed by histological evaluation and semi-quantitative analysis, suggested the immunomodulatory effect of vitamin D on the expression of IL-33 and IL-37. The minimal expression or absence of IL-33 and IL-37 expression in stented arteries is suggestive of an attenuated inflammatory response in stented arteries, compared to balloon angioplasty. The decreased IL-33 expression in the sufficient and supplemented microswine could be a potential mechanism for controlling the inflammatory process and neointima formation leading to attenuated luminal narrowing of the coronary artery. Overall, these results support supplementation of vitamin D to attenuate inflammation, neointima formation, and restenosis.

Lipotoxicity-associated inflammation is prevented by guarana (Paullinia cupana) in a model of hyperlipidemia.

Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory and antioxidant effects, which may prevent chronic diseases caused by changes in lipid profile. Thus, this study aims to evaluate the effect of guarana powder (Paullinia cupana) in the purine metabolism and inflammatory profile in lymphocytes and serum of rats with Poloxamer-407-induced hyperlipidemia. Pretreatment with guarana 12.5, 25, and 50 mg/kg/day or caffeine (0.2 mg/kg/day) by gavage was applied to adult male Wistar rats for a period of 30 days. As a comparative standard, we used simvastatin (0.04 mg/kg) post-induction. Hyperlipidemia was acutely induced with intraperitoneally injection of Poloxamer-407 (500 mg/kg). Guarana powder and caffeine increased the activity of the E-NTPDase (ecto-apyrase), and all pretreatments decreased the E-ADA (ecto-adenosine deaminase) activity, reducing the inflammatory process caused by lipotoxicity. In hyperlipidemic rats, ATP levels were increased while adenosine levels were decreased, guarana and caffeine reverted these changes. Guarana powder, caffeine, and simvastatin also prevented the increase in INF-γ and potentiated the increase in IL-4 levels, promoting an anti-inflammatory profile. Guarana promoted a more robust effect than caffeine. Our results show that guarana powder and caffeine have an anti-inflammatory as seen by the shift from a proinflammatory to an anti-inflammatory profile. The effects of guarana were more pronounced, suggesting that guarana powder may be used as a complementary therapy to improve the lipotoxicity-associated inflammation.

Omega-3 polyunsaturated fatty acids: anti-inflammatory and anti-hypertriglyceridemia mechanisms in cardiovascular disease.

Cardiovascular disease (CVD) is the world's most recognized and notorious cause of death. It is known that increased triglyceride-rich lipoproteins (TRLs) and remnants of triglyceride-rich lipoproteins (RLP) are the major risk factor for CVD. Furthermore, hypertriglyceridemia commonly leads to a reduction in HDL and an increase in atherogenic small dense low-density lipoprotein (sdLDL or LDL-III) levels. Thus, the evidence shows that Ω-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have a beneficial effect on CVD through reprogramming of TRL metabolism, reducing inflammatory mediators (cytokines and leukotrienes), and modulation of cell adhesion molecules. Therefore, the purpose of this review is to provide the molecular mechanism related to the beneficial effect of Ω-3 PUFA on the lowering of plasma TAG levels and other atherogenic lipoproteins. Taking this into account, this study also provides the TRL lowering and anti-inflammatory mechanism of Ω-3 PUFA metabolites such as RvE1 and RvD2 as a cardioprotective function.

Effects of Resistant Starch Ingestion on Postprandial Lipemia and Subjective Appetite in Overweight or Obese Subjects.

Reports surrounding the role of resistant starch (RS) on postprandial lipemia in humans are scarce. The aim of the present study is to examine the effects of resistant starch on the postprandial lipemic response, subjective measures of appetite, and energy intake in overweight and obese subjects. In a randomized, single-blind, crossover study, 14 overweight/obese participants ate a high-fat breakfast (679 kcal, 58% from fat) and a supplement with native banana starch (NBS), high-amylose maize starch (HMS), or digestible maize starch (DMS) on three separate occasions. All supplements provided were matched by the available carbohydrate content, and the RS quantity in NBS and HMS supplements was identical. Appetite was estimated using visual analogue scale (VAS) and an ad libitum test meal. Postprandial glycemia, triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, and insulin excursions did not differ between treatments. Subjective appetite measures of satiety were significantly increased after HMS; however, no effects on energy intake were observed during the ad libitum test meal. These findings suggest that a single acute dose of RS cannot be expected to improve postprandial lipemia in subjects with overweight or obesity on a high-fat meal. However, the potential benefits of long-term supplementation should not be ruled out based on these results.

Oligomer Procyanidins from Lotus Seedpod Regulate Lipid Homeostasis Partially by Modifying Fat Emulsification and Digestion.

Dietary polyphenols have shown hypolipidemic effects by reducing triglyceride absorption. The mechanisms may involve modifying fat emulsion during digestion in the gastrointestinal tract and suppressing lipase during hydrolysis in the small intestine. In an in vivo study, lotus seedpod oligomeric procyanidin (LSOPC) decreased total serum triglyceride and total cholesterol and elevated the high-density lipoprotein level in the hyperlipidemic rat model. In addition, LSOPC suppressed de novo lipogenesis-related gene expressions. In an in vitro study, the LSOPC-enriched emulsion decreased the mean droplet size from 0.36 to 0.33 µm and increased the viscosity of the emulsion. Moreover, the LSOPC-enriched emulsion improved the antioxidant properties. A digestion model was developed and showed that the particle size of the LSOPC-enriched emulsion increased in the oral cavity. However, an increase and then a significant drop of the particle size was measured in the stomach and small intestine. The free fatty acid release rate was decreased in the LSOPC-enriched emulsion partly ascribed to the inhibition of lipase by LSOPC.

Mitigating effects of antioxidant properties of Artemisia herba alba aqueous extract on hyperlipidemia and oxidative damage in alloxan-induced diabetic rats.

Chronic hyperglycemia and excess reactive oxygen species overproduced in diabetes were associated with oxidative stress, led to continuous injury and functions damage to different organs: eyes, kidneys, neural and cardiovascular system. The present study was undertaken to evaluate the protective effect of Artemisia herba alba (AHA) leaf powder against alloxane-induced oxidative damage in diabetic rats. Rats were randomly divided into four groups: Group I controls received saline solution 9%; Group II was treated with 150 mg alloxane/(kg body weight) administered by intraperitoneal. Rats of Group III have received saline solution and treated with 400 mg AHA/(kg body weight). Animals of Group IV were treated with alloxane and AHA. Alloxane exposure led to increased blood glucose, total cholesterol, triglycerides, malondialdehyde, and a decrease in the antioxidants enzymes activities (catalase, glutathione peroxidase and glutathione-S-transferase). Administration of AHA aqueous extract ameliorated these parameters. These results demonstrate that AHA ameliorates hyperglycemia, hyperlipidemia and oxidative damage in alloxan-induced diabetes in rats.

Polysaccharides from Tetrastigma hemsleyanum Diels et Gilg: Extraction optimization, structural characterizations, antioxidant and antihyperlipidemic activities in hyperlipidemic mice.

In this study, a novel polysaccharide TDGP-3 from Tetrastigma hemsleyanum Diels et Gilg was extracted by enzymolysis-ultrasonic assisted extraction (EUAE) method and its antioxidant and hypolipidemic activities were evaluated. With a molecular weight of 3.31 × 105 Da, TDGP-3 was composed of 1,4-Glcp, 1,4-Glap and 1,3,6-Manp linkage in the main chain. TDGP-3 showed potential effects on relieving hyperlipidemia and preventing oxidative stress, reflecting by regulating blood lipid levels (TC, TG, HDL-C and LDL-C), decreasing the contents of MDA in liver, restoring the activities of hepatic antioxidant enzymes (SOD, GSH-Px and CAT). The results clearly indicated that the TDGP-3 possesses a potent hypolipidemic activity and might be used for hyperlipidaemia treatment.

Physicochemical properties of polysaccharides separated from Camellia oleifera Abel seed cake and its hypoglycemic activity on streptozotocin-induced diabetic mice.

Two homogeneous polysaccharide fractions named SCP-1 (7.16 × 106 Da) and SCP-2 (2.00 × 104 Da) were purified by DEAE-52 cellulose and Sephadex G-200 column chromatography successively from Camellia oleifera Abel seed cake. They were characterized by Fourier transformed infrared (FT-IR), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy and differential scanning calorimetry (DSC). The monosaccharide compositions of SCP-1 were d­mannose, d­glucose and l­xylose with a molar ratio of 1.77:0.93:1 and that of the SCP-2 were d­mannose, l­rhamnose, d­glucose and l­xylose with a molar ratio of 5.27:1.21:0.16:1. Animal experiments suggested that the plasma glucose levels in hyperglycemia mice were reduced by 11.34%, 30.70%, 46.83% after administration of high, medium and low doses of SCP-1, and reduced by 16.67%, 23.93% and 33.00% after administration of high, medium and low doses of SCP-2, respectively. SCP-1 and SCP-2 also increased the activities of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), as well as decreased the content of malondialdehyde (MDA) in the hyperglycemia mice. These results suggested that SCP-1 and SCP-2 possessed strong hypoglycemic activities in streptozotocin-induced model mice. In addition, the hypoglycemic activity of SCP-1 was stronger than that of SCP-2.

Aqueous Extract of Humulus japonicus Attenuates Hyperlipidemia and Fatty Liver in Obese Mice.

In this study, the effects of Humulus japonicus (HJ) aqueous extract on 3T3-L1 preadipocytes and HepG2 cells (in vitro model) as well as on C57BL/6 mice fed on high-fat diet (HFD) (in vivo model) were evaluated. Mice fed on HFD for 12-weeks were taken the HJ water extract (HJW) at various doses, 50, 150, and 250 mg/kg, orally for 8 weeks. We have noticed the accumulation of fat globules in preadipocytes and HepG2 cells using Oil Red O staining. In addition, supplementation with HJW considerably inhibited the weight gain, lipid accumulation, and adipogenesis and decreased the size of subcutaneous adipocytes in 3T3-L1 adipocytes. Furthermore, treatment with HJW improved hyperlipidemia via decreasing the levels of serum triglyceride (TG) and low-density lipoproteins as well as the atherogenic index. Supplementation with HJW could attenuate HFD-induced lipid accumulation, increase the mRNA expressions of fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD1), and would elevate the levels of serum aspartate aminotransferase and alanine aminotransferase in mice liver. The levels of TG and FAS mRNA in HepG2 cells treated with palmitate were reduced in a dose-dependent manner. In sum, HJW could alleviate the HFD-induced obesity and decrease the dyslipidemia profiles; the keys that could contribute to cardiovascular and nonalcoholic liver diseases.

Hypolipidemic and Hepatoprotective Effects of a Polyprenol-Containing Drug in Patients with Acute Coronary Syndrome.

In a double-blind placebo-controlled trial POLYNCOR (registration No. NCT03122340 at clinicaltrials.gov ), lipid-lowering and hepatoprotective effects of polyprenol-containing drug Ropren were evaluated in patients with acute coronary syndrome. After 2-months therapy, total cholesterol and ALT in the patients receiving Ropren were significantly (p<0.05) lower than in the control group. The number of patients who needed to discontinue or reduce the dose of atorvastatin due to an increase in the level of transaminases in the main group was significantly (p<0.05) lower than in the control group: 0 (0%) vs. 5 (33.3%). The more pronounced decrease in cholesterol level and hepatoprotective effect of Ropren allowed recommending this preparation to patients with acute coronary syndrome in addition to standard therapy.

Hypolipidemic effect and protection ability of liver-kidney functions of melanin from Lachnum YM226 in high-fat diet fed mice.

In the present study, we investigated the hypolipidemic properties of melanin from Lachnum YM226 (LM) in high-fat diet induced hyperlipidemic mice. After the hyperlipidemic model was established, mice were randomly divided into six groups, as follows: normal control group (NC), hyperlipidemic control group (HC), positive control group (7 mg kg-1 d-1 simvastatin) (PC) and LM groups (50, 100 and 200 mg kg-1 d-1 denoted as LM-50, LM-100 and LM-200, respectively). Subsequently, the body weight, organ indices, lipid metabolism, antioxidant properties and liver-kidney functions of the mice were examined. Moreover, the activities of lipoprotein metabolism enzymes in serum and liver tissue were examined to study the feasible mechanism. The results imply that LM could effectively reduce body weight, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and atherogenic index (AI), and increase high density lipoprotein cholesterol (HDL-C). Moreover, treatment with LM also increased the antioxidant enzymes activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and reduced malondialdehyde (MDA) content relative to the HC group. In addition, the liver and kidney damage indices such as alanine aminotransferase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), creatinine (CRE), blood urea nitrogen (BUN) and uric acid were lowered. LM administration also significantly corrected disturbances of liver-kidney functions with no fatty deposits in the liver, resulting in a protective effect against renal histological alteration. The hypolipidemic effect occurred partly due to the regulation of hepatic lipase (HL) and lipoprotein lipase (LPL) in serum and liver to markedly decrease TG. This confirms the important role of LM in the prevention of hyperlipidemia.

Provision of Lifestyle Counseling and the Prescribing of Pharmacotherapy for Hyperlipidemia Among US Ambulatory Patients: A National Assessment of Office-Based Physician Visits.

BACKGROUND: An estimated 27.8% of the United States (US) population aged ≥20 years has hyperlipidemia, defined as total serum cholesterol of ≥240 mg/dL. A previous study of US physician office visits for hyperlipidemia in 2005 found both suboptimal compliance and racial/ethnic disparities in screening and treatment. OBJECTIVE: The aim was to estimate current rates of laboratory testing, lifestyle education, and pharmacotherapy for hyperlipidemia. METHODS: Data were derived from the US National Ambulatory Medical Care Survey (NAMCS), a nationally representative study of office-based physician visits, for 2013-2014. Patients aged ≥20 years with a primary or secondary diagnosis of hyperlipidemia were sampled. Study outcomes included receipt or ordering of total cholesterol testing, diet/nutrition counseling, exercise counseling, and pharmacotherapy prescription including statins, ezetimibe, omega-3 fatty acids, niacin, or combination therapies. RESULTS: Compared with previously reported results for 2005, rates of pharmacotherapy have remained static (52.2 vs. 54.6% for 2005 and 2013-2014, respectively), while rates of lifestyle education have markedly declined for diet/nutrition (from 39.7 to 22.4%) and exercise (from 32.1 to 16.0%). Lifestyle education did not vary appreciably by race/ethnicity in 2013-2014. However, rates of lipid testing were much higher for whites (41.6%) than for blacks (29.9%) or Hispanics (34.2%). Tobacco education was ordered/provided in only 4.0% of office visits. CONCLUSION: Compliance with guidelines for the screening and treatment of hyperlipidemia remains suboptimal, and rates of lifestyle education have declined since 2005. There exists an urgent need for enhanced levels of provider intervention to reduce the morbidity and mortality associated with hyperlipidemia.

Hypolipidemic Activity of Quercus acutissima Fruit Ethanol Extract is Mediated by Inhibition of Acetylation.

The acetylation of histone and nonhistone proteins is associated with adipogenesis. The objective of the present study was to investigate whether an ethanol extract of Quercus acutissima fruit (QF) exhibits antiobesity effects through inhibition of acetylation in 3T3-L1 preadipocytes and high fat diet (HFD)-fed obese mice. We observed that QF acts as a histone acetyltransferase (HAT) inhibitor and that QF (400 µg/mL) markedly inhibits the activity of p300 and CREB-binding protein. QF (200 µg/mL) significantly attenuated lipid accumulation without apparent toxicity, which is likely attributable to a decrease in the expressions of lipogenic proteins, including fatty acid synthase, peroxisome proliferator-activated receptor gamma, sterol regulatory element-binding protein 1, and CCAAT-enhancer-binding proteins alpha that were otherwise increased by MDI (a hormonal cocktail containing methyl isobutylmethylxanthine, dexamethasone, and insulin). MDI increased the acetylation of total lysine residues in whole 3T3-L1 cell lysate, an effect that was reversed by QF treatment (200 µg/mL). To further confirm the antiobesity activity of QF, mice were fed with HFD supplemented with QF at 50 and 200 mg/kg body weight. Mice fed with HFD exhibited increased masses of body, liver, and retroperitoneal fat, an effect that was suppressed in the presence of QF supplementation. QF-mediated decreases in body weight were attributable to a decrease in the average size of lipid droplets, as well as lipid accumulation in retroperitoneal fat and the liver, respectively. QF-mediated reductions in the size of the lipid droplets in the retroperitoneal fat tissue were likely associated with decreased expression of DGAT2. Taken together, our observations suggest that QF acts as an HAT inhibitor and attenuates adipogenesis in 3T3-L1 preadipocytes, resulting in the mitigation of HFD-induced obesity.

Neuromotor Activity, Anxiety and Cognitive Function in the In Vivo Model of Alimentary Hyperlipidemia and Obesity.

Behavioral indicators characterizing specific features of the pathological process of alimentary-dependent diseases were studied using in vivo model of alimentary hyperlipidemia in rats and mice. Rats and mice of the control groups received balanced semisynthetic diet for 63 days; animals of the experimental groups received a diet with high fat content (30% dry weight), balanced or high-fat diet with fructose solution instead of water, balanced cholesterol-enriched diet (0.5% dry weight), or balanced cholesterol-enriched diet with fructose solution. During the experiment, the mass of food, consumed by the animals, was monitored daily. Muscle tone was assessed by the front paw grip strength on days 33 and 54 of the experiment. Anxiety was tested in the elevated plus maze on days 36 and 57. Behavior and memory were assessed by conditioned passive avoidance reflex on days 39, 40, and 61. A significant increase in muscle tone was revealed on day 54 in rats fed with a balanced diet with fructose, and in mice, that received a similar diet, supplemented with fructose and cholesterol. Anxiety in the second test (day 57) was significantly decreased in rats fed high-fat diet and increased in mice fed high fat diet and high fat diet with fructose. In the second test, additional amount of cholesterol in the diet was the factor that significantly improved both short-term and long-term memory in both species. In mice, in contrast to rats, addition of fructose, including combination with high-fat diet, significantly worsened short-term and long-term memory. Thus, dietary factors, contributing to alimentary dyslipidemia development in rats and mice, can significantly affect the indices of neuromotor activity, anxiety level and cognitive functions, and the nature and direction of these changes are largely species-specific.

No additional cholesterol-lowering effect observed in the combined treatment of red yeast rice and Lactobacillus casei in hyperlipidemic patients: A double-blind randomized controlled clinical trial.

OBJECTIVE: To observe the effect of combining red yeast rice and Lactobacillus casei (L. casei) in lowering cholesterol in patients with primary hyperlipidemia, the later has also been shown to remove cholesterol in in vitro studies. METHODS: A double-blind clinical trial was conducted to evaluate the cholesterol-lowering effect of the combination of red yeast rice and L. casei. Sixty patients with primary hyperlipidemia were recruited and randomized equally to either the treatment group (red yeast rice + L. casei) or the control group (red yeast rice + placebo). One red yeast rice capsule and two L. casei capsules were taken twice a day. The treatment lasted for 8 weeks, with an extended follow-up period of 4 weeks. The primary endpoint was a difference of serum low-density lipoprotein cholesterol (LDL-C) level at week 8. RESULTS: At week 8, the LDL-C serum level in both groups was lower than that at baseline, with a decrease of 33.85±26.66 mg/dL in the treatment group and 38.11±30.90 mg/dL in the control group; however, there was no statistical difference between the two groups (P>0.05). The total cholesterol was also lower than the baseline in both groups, yet without a statistical difference between the two groups. The only statistically signifificant difference between the two groups was the average diastolic pressure at week 12, which dropped by 2.67 mm Hg in the treatment group and increased by 4.43 mm Hg in the placebo group (P<0.05). The antihypertensive activity may be associated with L. casei. Red yeast rice can signifificantly reduce LDL-C, total cholesterol and triglyceride. CONCLUSION: The combination of red yeast rice and L. casei did not have an additional effect on lipid profifiles.

Low molecular weight fucoidan ameliorates streptozotocin-induced hyper-responsiveness of aortic smooth muscles in type 1 diabetes rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Low molecular weight fucoidan (LMWF) was prepared from Laminaria japonica Areschoug, a popular seafood and medicinal plant consumed in Asia. Chinese have long been using it as a traditional medicine for curing hypertension and edema. AIM OF THE STUDY: This study was intent to investigate the possible beneficial effect of LMWF on hyper-responsiveness of aortic smooth muscles instreptozotocin (STZ)-induced type 1 diabetic rats. MATERIALS AND METHODS: Sprague-Dawley rats were made diabetic by injection of STZ, followed by the administration of LMWF (50 or 100mg/kg/day) or probucol (100mg/kg/day) for 12 weeks. Body weight, blood glucose level, basal blood pressure, serum lipid profiles, oxidative stress, prostanoids production, and vasoconstriction response of endothelium-denuded aorta rings to phenylephrine were measured by Real time-PCR, Western blots, ELISA assay, and force myograph, respectively. RESULTS: LMWF (100mg/kg/day)-treated group showed robust improvements on STZ-induced body weight-loss, hypertension, and hyperlipidaemia as indicated by decreased serum level of total cholesterol, triglyceride, and low density lipoprotein cholesterol; while probucol, a lipid-modifying drug with antioxidant properties, displayed mild effects. In addition, LMWF appreciably ameliorated STZ-elicited hyper-responsiveness and oxidative stress in aortic smooth muscles as indicated by decreased superoxide level, increased glutathione content and higher superoxide dismutase activity. Furthermore, administration with LMWF dramatically prevented cyclooxygenase-2 stimulation and restored the up-regulation of thromboxane synthase and down-regulation of 6-keto-PGF1α (a stable metabolic product of prostaglandin I2) in the STZ-administered rats. CONCLUSION: This study demonstrates for the first time that LMWF can protect against hyperlipidaemia, hypertension, and hyper-responsiveness of aortic smooth muscles in type 1 diabetic rat via, at least in part, amelioration of oxidative stress and restoration of prostanoids levels in aortic smooth muscles. Therefore, LMWF can be a potential adjuvant treatment against cardiovascular complications in type 1 diabetes.

[Impact on the lipid level of obesity of spleen deficiency and damp blockage complicated by hyperlipemia treated with warm needling therapy and auricular acupuncture].

OBJECTIVE: To explore the efficacy on obesity of spleen deficiency and damp blockage pattern and hyperlipemia treated with warm needling therapy and auricular acupuncture and the effect mechanism of the combined treatment. METHODS: One hundred and ten patients of obesity of spleen deficiency and damp blockage pattern and hyperlipemia were randomized into an observation group and a control group, 55 cases in each one. Additionally, a healthy group (52 cases) was set up as the control. In the control group, the warm needling therapy was applied to Taibai (SP 3), Chongyang (ST 42), Yinlingquan (SP 9), Zusanli (ST 36), etc., once every two days. In the observation group, on the basic treatment as the control group, the auricular acupuncture was applied to Pi (CO13), Wei (CO4), Fei (CO14), Shen (CO10), etc., once every 2 to 3 days. The efficacy was evaluated after 3-month, treatment in the two groups. The observation was conducted on the obesity outcomes [body mass, obesity degree (A), body mass index (BMI), body fat percentage (F%)], blood-lipoids indicators [such as serum total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)], fat-islet endocrine axis outcomes [such as fasting plasma glucose (FPG) , fasting leptin (FLP), fasting insulin (FINS), insulin sensitivity index (ISI), insulin resistance index (Homa-IR) and insulin ß cell function index (Homa-ß)], as well as autonomic nerve function index (Y) before and after treatment in the patients of the two groups. The efficacy was assessed in the two groups. RESULTS: The total effective rate was 96.4% (53/55) in the observation group, better than 87.3% (48/55, P < 0.01) in the control group. For the improvements of the obesity indices, the differences were not significant between the two groups (all P > 0.05). Before treatment, the levels of TC, TG, LDL-C, FLP, FPG, FINS and Homa-IR in the two groups were all significantly higher than those in the healthy group (all P < 0.01), and the levels of HDL, ISI, Homa-ß and Y were significantly lower than those in the healthy group (all P < 0.01). After treatment, except Homa-ß, the other indices were all improved significantly (all P < 0.01). The results in the observation group were better than those in the control group (all P < 0.01). CONCLUSION: The patients of obesity of spleen deficiency and damp blockage pattern and hyperlipemia have the disturbances of lipid metabolism, "fat-islet endocrinal axis" function and automatic nerve function. The combined treatment of warm needling therapy and auricular acupuncture or simple warm needling therapy present the effects of weight reducing and lipid reducing. The effect of the combined treatment is better than simple warm needling therapy. The efficacy mechanism is probably relevant to the positive regulation of blood glucose, lipid metabolism, fat-islet endocrinal axis and automatic nerve function.

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.

The ergogenic supplement ß-hydroxy-ß-methylbutyrate (HMB) attenuates insulin resistance through suppressing GLUT-2 in rat liver.

This study investigates the effect of the ergogenic supplement ß-hydroxy-ß-methylbutyrate (HMB) on insulin resistance induced by high-fructose diet (HFD) in rats. Male Sprague Dawley rats were fed 60% HFD for 12 weeks and HMB (320 mg·kg(-1)·day(-1), orally) for 4 weeks. HFD significantly increased fasting insulin, fasting glucose, glycosylated hemoglobin (HBA1C), liver glycogen content, and homeostasis model assessment of insulin resistance (HOMA-IR) index, while it decreased glucose and insulin tolerance. Furthermore, HFD significantly increased serum triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL-C) levels, while it significantly decreased high density lipoprotein cholesterol (HDL-C). Moreover, HFD significantly increased mRNA expression of glucose transporter type-2 (GLUT-2), the mammalian target of rapamycin (mTOR), and sterol regulatory element-binding protein-1c (SREBP-1c) but decreased peroxisome proliferator-activated receptor-alpha (PPAR-α) in liver. Aortic relaxation to acetylcholine (ACh) was impaired and histopathology showed severe hepatic steatosis. HMB significantly increased insulin tolerance and decreased fasting insulin, HOMA-IR, HBA1C, hepatic glycogen content, serum TG, LDL-C, and VLDL-C. Additionally, HMB enhanced ACh-induced relaxation, ameliorated hepatic steatosis, and decreased mRNA expression of GLUT-2. In conclusion, HMB may attenuate insulin resistance and hepatic steatosis through inhibiting GLUT-2 in liver.

Nifedipine Treatment for Hypertension is Associated with Enhanced Lipolytic Activity and Accelerated Clearance of Postprandial Lipemia.

Hypertension, advanced age, postprandial hyperlipidemia, and insulin resistance are major risk factors for atherosclerosis. The calcium channel blocker nifedipine is reported to ameliorate insulin resistance possibly by activating PPARγ. This is expected to become accentuated in elderly individuals due to age-related insulin resistance. Insulin resistance modulates lipoprotein metabolism. Therefore, we reasoned that nifedipne offers the potential for improving postprandial lipemia in association with increasing age. We studied the effect of nifedipine on fasting lipids, postprandial lipemia, insulin sensitivity, and plasma lipolytic activity in 24 and 15 hypertensive subjects aged 70-75 years and 40-45 years, respectively. As expected, nifedipine significantly lowered systolic and diastolic blood pressure. Nifedipine decreased fasting triglyceride level (23%) and increased HDL-C (15%) in the elderly group. At baseline, postprandial triglyceride levels were remarkably elevated in elderly compared to younger patients (1 288±798 vs. 501±260 mg·dl(-1)·h, p<0.05), as was retinyl palmitate (surrogate marker for intestinally-derived cholesterol) in the chylomicrons (45.0±26.5 vs. 23.4±10.6 mg·l(-1)·h, p<0.05) and chylomicron remnant (15.2±5.4 vs. 11.7±4.7 mg·l(-1)·h, p<0.05) fractions. Importantly, while the level of chylomicron remnants in the group of younger subjects remained unchanged after treatment, nifedipine was associated with a significantly decreased chylomicron remnants retinyl palmitate in the elderly group, which dropped to levels, observed in younger subjects. This was accompanied by enhanced insulin sensitivity and augmented plasma lipolytic activity. The present work suggests that nifedipine has favorable metabolic effects that are beyond the known enhancement of insulin sensitivity. The improvement in postprandial lipidemia by nifedipine may add to its anti-atherogenic effects in hypertensive patients.