There is an increasing number of novel antilipidemic therapies under consideration. The putative hypolipidemic effect of N-acetylcysteine (NAC) and sesame oil was studied in a mouse model of dietary-induced hypercholesterolemia. Male C57bl/6 mice were assigned to the following groups: (NC) control group, (HC) group receiving test diet supplemented with 2% cholesterol and 0.5% cholic acid for 8 weeks, (HCN) group receiving the test diet with NAC supplementation (230 mg/kg p.o.) and (HCS) group fed the test diet enriched with 10% sesame oil. Total serum cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were assayed at the beginning and at the end of the experiment. Total peroxides and nitric oxide (NO) levels were measured in the serum at the end of the experiment. Hepatic and aortic lesions were evaluated by haematoxylin-eosin staining. Higher serum levels of total and LDL-cholesterol were recorded in all groups fed the high cholesterol diet. The HCN group presented reduced lipid levels compared to HC and HCS groups. No differences were observed between HCS and HC groups. Peroxide content in serum was markedly increased in mice consuming high cholesterol diet. NAC and sesame oil administration led to a significant decrease of serum lipid peroxidation in the levels of control group, whereas only NAC restored NO bioavailability. In terms of liver histology, the lesions observed in HCN group were less severe than those seen in the other high cholesterol groups. Co-administration of NAC, but not sesame oil, restored the disturbed lipid profile and improved hepatic steatosis in the studied diet-induced hypercholesterolemic mice. Both agents appear to ameliorate serum antioxidant defense.

Hyperlipidemia and stress are important factors affecting cardiovascular health in middle-aged individuals. We investigated the effects of N-acetylcysteine (NAC) and sesame oil on the lipidemic status, liver architecture and the hypothalamic-pituitary-adrenal (HPA) axis of middle-aged mice fed a cholesterol-enriched diet. We randomized 36 middle-aged C57bl/6 mice into 6 groups: a control group, a cholesterol/cholic acid diet group, a cholesterol/cholic acid diet group with NAC supplementation, a cholesterol/cholic acid diet enriched with 10% sesame oil and two groups receiving a control diet enriched with NAC or sesame oil. NAC administration prevented the onset of the disturbed lipid profile, exhibiting decreased lipid peroxidation and alkaline phosphatase (ALP) levels, restored nitric oxide bioavailability and reduced hepatic damage, compared to non-supplemented groups. High-cholesterol feeding resulted in increased hypothalamic glucocorticoid receptors (GR) levels, while NAC supplementation prevented this effect. NAC supplementation presented significant antioxidant capacity by means of preventing serum lipid status alterations, hepatic damage, and HPA axis disturbance due to high-cholesterol feeding in middle-aged mice. These findings suggest a beneficial preventive action of plant-derived antioxidants, such as NAC, on lipid metabolism and on the HPA axis.

Mice are widely used in studies investigating the effect of diet on metabolic risk factors, such as lipid profiles and plasma glucose levels. An important factor that is usually not taken into account is the biological age of the experimental models. The up-to-date identified experimental confounders do not cover all the parameters that may affect the results of animal studies. The aim of this study was to investigate the effects of a high-fat diet on the metabolic profile, hepatic and renal function in mice of differing ages. For this purpose two groups of male C57BL/6J mice were used, consisting of 10-week-old mice and 54-week-old mice in each group. Both groups followed identical high-fat diets for 12 weeks. The younger mice showed smaller increases in body weight, serum total cholesterol, glucose and urea levels while they had higher increases in high-density lipoprotein cholesterol levels than the older mice. Our results indicate the necessity to consider an experimental animal’s age as a confounding factor when researching or interpreting metabolic studies. Age adjustment is warranted in all animal research while a uniform approach regarding the age of the animal models should be applied in experimental studies.

Atherosclerosis is a chronic inflammatory disease that is promoted, among others, by pro-inflammatory cytokines such as IL-1β and IL-18 produced by NLRP 3 inflammasome. Development of atherosclerotic lesions is also affected by leptin. Furthermore, inflammasome’s action is interfered with other inflammatory diseases, like diabetes. On the other hand, colchicine is reported to act as anti-inflammatory agent inhibiting inflammasome’s action and stabilizing atherosclerotic lesions. The purpose of this study is to investigate the effect of per os colchicine on the de novo formation of atherosclerotic lesions and on the levels of IL-18, leptin and insulin in cholesterol-fed rabbits. Twenty-three male, 2 months old New Zealand White rabbits, were seperated in 3 groups and were fed with different types of diet for 7 weeks: standard, cholesterol 1% w/w and cholesterol 1% w/w plus colchicine 2 mg/kg body weight. Blood was collected for biochemical measurements and conduction of ELISA for leptin, IL-18 and insulin. Histologic examination of stained with eosin and hematoxylin aorta specimens was performed. Aortic intimal thickness was evaluated using image analysis. The statistical analysis included non-parametric tests: a) paired-sample Wilcoxon test, b) Spearman correlation coefficient and c) Kruscal-Wallis test. Triglerycide levels were decreased in cholesterol plus colchicine group in the end of the experiment (p < 0.05), whereas the cholesterol group had increased levels. No statistical differences were observed in the levels of IL-18, leptin and insulin between groups. Likewise, there was neither any correlation between IL-18, leptin and intima thickness nor between IL-18 and glucose and between leptin and weight. In cholesterol and colchicine group there was a strong positive correlation between IL-18 and insulin levels in the 4th week (r s = .66, n = 10, p < 0.05), whereas in the 7th week this correlation became strong negative (r s = −.86, n = 10, p < 0.05). Finally, intima thickness in the ascending and thoracic aorta of the cholesterol and colchicine group was significantly greater than that of the other groups (p < 0.05). Per os administration of colchicine did not influence atherosclerosis progression in cholesterol-fed rabbits, levels of IL-18, insulin and leptin. We encountered the attenuating role of colchicine on TG levels.

Visceral fat possesses the most detrimental potential for cardiovascular morbidity through the release of adipokines, as well as metabolic and proinflammatory mediators, which adversely affect metabolic and vascular homeostasis. Among the different types of visceral adipose tissue, mesenteric fat is considered particularly detrimental, due to its close proximity to the portal circulation, affecting directly the liver, which is the main regulator of body metabolic homeostasis. Mesenteric fat can be reliably estimated using abdominal ultrasonography, the only available imaging method able to depict individual mesenteric leaves. Aim of the present study was to investigate the correlation of mesenteric fat thickness (MFT) with serum apolipoprotein levels in patients undergoing digital subtraction angiography in a single center. 35 male patients with peripheral arterial disease were examined. After careful examination of the periumbilical area, the mesenteric leaves were identified. The maximal distance between each pair of sequential leaves was measured, and the mean value of the three thickest leaves was determined as the mesenteric fat thickness. Six apolipoprotein fasting serum concentrations were measured using a Luminex proteomics platform (xMAP Multiplex immunoassay): apolipoprotein A-I (apoAI), apolipoprotein A-II (apoAII), apolipoprotein B (apoB), apolipoprotein C-II (apoCII), apolipoprotein C-III (apoCIII) and apolipoprotein E (apoE). MFT correlated with apoAII and apoB serum concentrations. The correlations with apoAII and apoB remained significant following correction for BMI. No correlations were noted between MFT and serum apoAI, apoCII, apoCIII or apoE levels before or after adjustment for BMI. Our study indicates that MFT is significantly correlated with the concentration of atherogenic low density lipoproteins particles, as well as with apoAII, a determinant of free fatty acids levels. No correlation was observed between mesenteric fat thickness and very low density lipoprotein or chylomicron particles concentration.