Triple-Knockout, Synuclein-Free Mice Display Compromised Lipid Pattern

Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. These are among aspects of decreased synuclein functions that are still poorly acknowledged especially in regard to pathogenesis in Parkinson’s disease. Here, we aimed to add to existing knowledge of synuclein deficiency (i.e., the lack of all three family members), with respect to changes in fatty acids and lipids in plasma, liver, and two brain regions in triple synuclein-knockout (TKO) mice. We describe changes of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and non-esterified fatty acids in plasma of synuclein free mice. In midbrain, we observed counterbalanced changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER). We also recorded a notable reduction in ethanolamine plasmalogens in the midbrain of synuclein free mice, which is an important finding since the abnormal ether lipid metabolism usually associated with neurological disorders. In summary, our data demonstrates that synuclein deficiency results in alterations of the PUFA synthesis, storage lipid accumulation in the liver, and the reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members causes more profound changes in lipid metabolism than changes previously shown to be associated with γ-synuclein deficiency alone. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.

Biological and pharmacological effects of gamma-oryzanol: an updated review of the molecular mechanisms

Background: Gamma-oryzanol (γ-oryzanol) is one of the rice bran oil (RBO) compounds, known as a principal food source throughout the world. In recent numerous experimental studies, γ-oryzanol has been revealed to have several useful pharmacological properties such as antioxidant, anti-inflammatory, anticancer, anti-diabetic, ameliorating menopausal unpleasant symptoms, cholesterol-lowering, plasma lipid pattern improving, etc. Methods: In this study we reviewed the scientific literature published up until 2020, which have evaluated the biological and pharmacological activity of gamma-oryzanol. This review summarizes the published data found in PubMed, Science Direct and Scopus. Results & Conclusion: The present review attempts to summarize the most related articles about the pharmacologic and therapeutic potential from recent studies on γ-oryzanol to gain insights for design further studies to achieve new evidence which confirm observed effects.

Triple-knockout, synuclein-free mice display compromised lipid pattern

Background: Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. All members of the synuclein family interact robustly with lipid membranes, and appear to be important for the physiological functions of proteins while influencing the pathological aggregation of α-synuclein. Methods: The following tissues were used for lipid and fatty acid analysis: plasma, liver and two brain areas (cortex and midbrain). Lipid classes were separated using thin-layer chromatography. Fatty acids were analysed using gas chromatography. Results: We describe the importance of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and circulated plasma non-esterified fatty acids in synuclein free mice. In midbrain, observed changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER) were counterbalanced. In midbrain, we recorded a notable reduction in ethanolamine plasmalogens in synuclein free mice and consider this an important finding considering the abnormal ether lipid metabolism usually associated with neurological disorders.Conclusions: In summary, our data demonstrate that synuclein deficiency can result in alterations of PUFA synthesis, storage lipid accumulation in liver, and reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members resulted in more pronounced lipid modifications then previously showed by us γ-synuclein deficiency. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.

Thyroid and Lipid Status in Guide Dogs During Training: Effects of Dietary Protein and Fat Content

Nutrition plays a leading role that most influences thyroid response and energetic metabolism. Aim was to compare the effect of diet on thyroid and lipid status in guide dogs during a 12-weeks training period. Eight Labrador Retrievers were divided into two groups homogeneous for sex, age, body weight, and Body Condition Score (BCS) and fed two commercial diets one, HPF, characterized by low-carbohydrate/high-protein/high-fat (29%:39%:19% as-fed) and the other, LPF, by high-carbohydrate/low-protein/low-fat (50%:24%:12% as-fed) content. The serum thriiodothyronine (T3), thyroxine (T4), cholesterol (CHOL), triglycerides (TAGs) and non-esterified fatty acids (NEFA) were determined at Day 0, 28, 56, and 84, before the daily training. Statistical model included the effects of Diet (HPF vs. LPF) and Time (Day 0 to Day 84), and their interaction. In the HPF group, Diet significantly (p < 0.01) increased T4, CHOL, and TAGs and decreased NEFA. In both groups, Time significantly (p < 0.05) increased T4 and TAGs, CHOL at Day 28, and NEFA at Day 56. The interaction did not influence serum hormones and lipid pattern. The adjustments in thyroid and lipid responses to moderate exercise in HPF group were driven mainly by the nutrient composition of the diet in relation to the involvement of metabolic homeostasis.

Features and main problems of treating patients with high and very high cardiovascular risk with statins in real clinical practice (according to the data of the “PRIORITET” research)

Aim. To determine the features and main problems of statin therapy, as well as assess the possibility of achieving the target level of lipid pattern in patients with high and very high cardiovascular risk (CVR) in real clinical practice.Material and methods. The design of the “PRIORITET” observational program is an open observational study. Patients with high and very high CVR were divided into 3 groups in accordance with the initial data: (1) not taking statins, (2) taking statins, but not reaching the target low-density lipoprotein cholesterol (LDL-C) level, (3) taking statins with the achievement of the target LDL-C level, which is justified in replacing the statin inside the class — adverse effects (AE), high price, etc. Within 12 weeks 3 visits of patients to hospitals were carried out: baseline visit (B0), visit 1 month after the study initiation (B1) and visit 3 months after the study initiation (B3). The choice of atorvastatin or rosuvastatin was assessed by the doctors.Results. Groups 1, 2 and 3 included 112, 170 and 16 people, respectively. At B0, 145 (48,7%) patients were prescribed atorvastatin, and 153 (51,3%) — rosuvastatin. Three people dropped out of the study to B3, 295 patients completed the program. Lipid pattern of 285 patients were analyzed: 121 (41%) people (101 with very high CVR and 20 with high CVR) achieved the target LDL-C level, the remaining 164 (59%) patients (CVR — 156 and 8, respectively) — no. The most pronounced dynamics of LDL=C level was revealed in group 1, the differences between group 1 and groups 2 and 3 are highly statistically significant (p<0,0001). There were no differences in the frequency of reaching the target LDL-C level between patients taking atorvastatin or rosuvastatin. The target level of LDL-C (p=0,003) in the treatment of rosuvastatin in patients with high CVR was reached significantly more often than in patients with very high CVR. Also 3 non-serious AEs were reported. On average, in 9% of cases, reaching the target level of LDL-С during visits B1 and B3 was wrong interpreted by the attending physicians.Conclusion. The main problems of statin therapy in real clinical practice are the wrong interpretation of reaching the target level of LDL-C, inertness of doctors in titrating of statins doses and achieving the target level of lipid pattern. It may be the cause of reduced efficiency and deterioration of lipid-lowering therapy results in patients with high and very high CVR. The results of the “PRIORITET” study demonstrated the possibility of improving the practice of statins use and its accordance with clinical guidelines.Skibitsky V. V. on behalf of the working group of the “PRIORITET” researchWorking Group of the “PRIORITET” study: Voronina V. P. (Moscow), Zelenova T. I. (Moscow), Sladkova T.A. (Moscow), Alekseeva A. I. (Tula), Barabanova T. Yu. (Tula), Zotova A. S. (Tula), Kolomeitseva T. M. (Tula), Prikhod’ko T. N. (Tula), Pazelt E. A. (Nizhny Novgorod), Khramushev N. Yu. (Nizhny Novgorod), Skibitsky A. V. (Krasnodar), Alekseeva V. V. (Saratov), Lazareva E. V. (Saratov).

Features and main problems of treating patients with high and very high cardiovascular risk with statins in real clinical practice (according to the data of the “PRIORITET” research)

Aim. To determine the features and main problems of statin therapy, as well as assess the possibility of achieving the target level of lipid pattern in patients with high and very high cardiovascular risk (CVR) in real clinical practice.Material and methods. The design of the “PRIORITET” observational program is an open observational study. Patients with high and very high CVR were divided into 3 groups in accordance with the initial data: (1) not taking statins, (2) taking statins, but not reaching the target low-density lipoprotein cholesterol (LDL-C) level, (3) taking statins with the achievement of the target LDL-C level, which is justified in replacing the statin inside the class — adverse effects (AE), high price, etc. Within 12 weeks 3 visits of patients to hospitals were carried out: baseline visit (B0), visit 1 month after the study initiation (B1) and visit 3 months after the study initiation (B3). The choice of atorvastatin or rosuvastatin was assessed by the doctors.Results. Groups 1, 2 and 3 included 112, 170 and 16 people, respectively. At B0, 145 (48,7%) patients were prescribed atorvastatin, and 153 (51,3%) — rosuvastatin. Three people dropped out of the study to B3, 295 patients completed the program. Lipid pattern of 285 patients were analyzed: 121 (41%) people (101 with very high CVR and 20 with high CVR) achieved the target LDL-C level, the remaining 164 (59%) patients (CVR — 156 and 8, respectively) — no. The most pronounced dynamics of LDL=C level was revealed in group 1, the differences between group 1 and groups 2 and 3 are highly statistically significant (p<0,0001). There were no differences in the frequency of reaching the target LDL-C level between patients taking atorvastatin or rosuvastatin. The target level of LDL-C (p=0,003) in the treatment of rosuvastatin in patients with high CVR was reached significantly more often than in patients with very high CVR. Also 3 non-serious AEs were reported. On average, in 9% of cases, reaching the target level of LDL-С during visits B1 and B3 was wrong interpreted by the attending physicians.Conclusion. The main problems of statin therapy in real clinical practice are the wrong interpretation of reaching the target level of LDL-C, inertness of doctors in titrating of statins doses and achieving the target level of lipid pattern. It may be the cause of reduced efficiency and deterioration of lipid-lowering therapy results in patients with high and very high CVR. The results of the “PRIORITET” study demonstrated the possibility of improving the practice of statins use and its accordance with clinical guidelines.Skibitsky V. V. on behalf of the working group of the “PRIORITET” researchWorking Group of the “PRIORITET” study: Voronina V. P. (Moscow), Zelenova T. I. (Moscow), Sladkova T.A. (Moscow), Alekseeva A. I. (Tula), Barabanova T. Yu. (Tula), Zotova A. S. (Tula), Kolomeitseva T. M. (Tula), Prikhod’ko T. N. (Tula), Pazelt E. A. (Nizhny Novgorod), Khramushev N. Yu. (Nizhny Novgorod), Skibitsky A. V. (Krasnodar), Alekseeva V. V. (Saratov), Lazareva E. V. (Saratov).