The mechanisms involved in the decline of high-density lipoprotein (HDL) levels at a higher dose of atorvastatin have not yet been elucidated. We investigated the effects of atorvastatin on HDL-apolipoprotein (apo) A-I metabolism in dogs, a species lacking cholesteryl ester transfer protein activity.Seven ovariectomized normolipidaemic female Beagle dogs underwent a primed constant infusion of [5,5,5-(2)H(3)] leucine to determine HDL-apo A-I kinetics before and after atorvastatin treatment (5 mg kg(-1) d(-1) for 6 weeks). Plasma lipoprotein profiles, activity of HDL-modifying enzymes involved in reverse cholesterol transport and hepatic scavenger receptor class B type I (SR-BI) expression were also studied.Atorvastatin treatment decreased HDL-cholesterol levels (3.56 +/- 0.24 vs. 2.64 +/- 0.15 mmol L(-1), P < 0.05). HDL-triglycerides were not affected. HDL-phospholipids levels were decreased (4.28 +/- 0.13 vs. 3.29 +/- 0.13 mmol L(-1), P < 0.05), as well as phospholipids transfer protein (PLTP) activity (0.83 +/- 0.05 vs. 0.60 +/- 0.05 pmol microL(-1) min(-1), P < 0.05). Activity of lecithin: cholesterol acyl transferase (LCAT), hepatic lipase (HL) and SR-BI expression did not change. HDL-apo A-I absolute production rate (APR) was higher after treatment (twofold, P < 0.05) as well as fractional catabolic rate (FCR) (threefold, P < 0.05). This resulted in lower HDL-apo A-I levels (2.36 +/- 0.03 vs. 1.55 +/- 0.04 g l(-1), P < 0.05). Plasma lipoprotein profiles showed a decrease in large HDL(1) levels, with lower apo A-I and higher apo E levels in this subfraction.Although a high dose of atorvastatin up-regulated HDL-apo A-I production, this drug also increased HDL-apo A-I FCR in dogs. This effect could be explained by a higher uptake of apo E-enriched HDL(1) by hepatic lipoprotein receptors.
Thymus atlanticus, an endemic plant of Morocco, is traditionally used as a liniment or a drink to treat various diseases. However, there are few available scientific data regarding its biological effects. In this connection, the present study aimed to investigate the hypolipidemic and antioxidant effects of aqueous extract and polyphenol fraction of Thymus atlanticus in Syrian golden hamsters treated with Triton WR-1339 (triton, 20 mg/100 g body weight). The hamsters orally received the extracts (400 mg/kg), and blood samples were collected after 24 h of treatment to determine plasma lipid, insulin, and fasting blood glucose levels. Plasma malondialdehyde level and plasma total antioxidant (TAS) were also evaluated. The T. atlanticus extracts significantly decreased triglycerides, total cholesterol, VLDL-C, and LDL-C and increased HDL-C when compared with the hyperlipidemic group. Both extracts suppressed the effect of the triton injection on TAS and reduced the level of plasma malondialdehyde. The extracts produced no significant change in the blood glucose level but effectively prevented the mild hyperinsulinemia induced by triton. These findings suggest that T. atlanticus may be a useful alternative treatment for the control of hyperlipidemia and its related diseases.
Non-alcoholic fatty liver disease represents the most common liver disease and is characterized by an excess of lipid accumulation in hepatocytes, mainly stored as triglycerides. Phaeodactylum tricornutum is a marine microalga, which is rich in bioactive molecules known to be hepatoprotective, such as n-3 long-chain polyunsaturated fatty acids and fucoxanthin. The aim of this study was to investigate the effects of a carotenoid extract from P. tricornutum in a cellular model of non-alcoholic fatty liver disease induced by palmitate treatment. The combined effects of carotenoids and lipids, especially n-3 long-chain polyunsaturated fatty acids, were also investigated by using a total lipophilic extract. HepG2 cells were exposed for 24 h to 250 µM palmitate with or without the addition of carotenoid extract (6 μg/mL) or total lipophilic extract (100 μg/mL). The addition of carotenoid extract or total lipophilic extract prevented the accumulation of triglycerides, total cholesterol and cholesterol esters. The carotenoid extract and total lipophilic extract also decreased the mRNA expression levels of genes involved in lipogenesis (ACACA, FASN, SCD and DGAT1) and cholesterol esterification (ACAT1/SOAT1). In addition, the total lipophilic extract also downregulated the LXR/NR1H3 and SREBF1 genes, which are involved in lipogenesis regulation. By contrast, the carotenoid extract increased the mRNA level of CPT1A, a β-oxidation related gene, and reduced the lipid droplet accumulation. In conclusion, this study highlights the preventive effects against non-alcoholic fatty liver disease of the two microalga extracts.
Dietary factors may affect lipid metabolism and thus impact cardiovascular disease development. The objective of this study was to analyze the effects of 8 wk ingestion of mineralized water compared with control on fasting and postprandial lipoproteins levels in hyperlipidemic men. Subjects (N=12) consumed mineralized water (Saint Yorre) or low mineralized Water (Ogeu) in random order for 8‐wk periods, separated by a 1‐wk washout. Lipoprotein lipids were assessed prior to (fasting) and following a standard meal for 8 h (postprandial). Fasting and postprandial plasma triglycerides (TG) were decreased following mineralized water compared to control (p<0.01 and <0.05, respectively). This decrease was related to a significant decrease in fasting and postprandial levels of very low‐density lipoprotein (VLDL) TG (respectively p<0.01 and p<0.05) and a slight decrease in fasting total cholesterol (TC) (p<0.1). High‐density lipoprotein cholesterol (HDL‐C) increased postprandially (p<0.05) following the mineralized water compared to the low mineralized water. The reduction in postprandial concentrations of VLDL TG and the increase in HDL‐C suggest improvements in liver lipid metabolism and postprandial lipemia, which may favorably affect cardiovascular health.
