Molecular mechanisms of the cytoprotector cramizol effect in the experimental dyslipidemia model

2020 ◽  
Vol 66 (4) ◽  
pp. 326-331
Author(s):  
A.V. Lizunov ◽  
I.V. Okunevich ◽  
A.A. Lebedev ◽  
E.R. Bychkov ◽  
L.B. Piotrovskiy ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Atherogenic Index ◽  
Blood Cholesterol ◽  
Lipid Lowering ◽  
Reference Drug ◽  
Hypolipidemic Agent ◽  
Experimentally Induced

The tested drug cramizol exhibits lipid-lowering and anti-atherogenic effects. Cramizol reduces blood cholesterol and triglycerides. It also increases HDL and reduces the atherogenic index in rats with the chronic dyslipidemia model induced by a hypercholesterol diet. Cramizol is effective as a hypolipidemic agent and its efficiency is comparable with the reference drug, phenofibrate. Cramizol increases expression of the ApoA1 and ApoC2 genes, and also reduces expression of the Scarb1 gene in rats with experimentally induced hyperlipidemia. These mechanisms could be the basis of its hypolipidemic and anti-atherogenic actions.

scholarly journals Therapies for the Treatment of Cardiovascular Disease Associated with Type 2 Diabetes and Dyslipidemia

2021 ◽  
Vol 22 (2) ◽  
pp. 660
Author(s):  
María Aguilar-Ballester ◽  
Gema Hurtado-Genovés ◽  
Alida Taberner-Cortés ◽  
Andrea Herrero-Cervera ◽  
Sergio Martínez-Hervás ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Leukocyte Adhesion ◽  
Experimental Studies ◽  
Lipid Lowering ◽  
Foam Cell Formation ◽  
Relevant Parameter

Cardiovascular disease (CVD) is the leading cause of death worldwide and is the clinical manifestation of the atherosclerosis. Elevated LDL-cholesterol levels are the first line of therapy but the increasing prevalence in type 2 diabetes mellitus (T2DM) has positioned the cardiometabolic risk as the most relevant parameter for treatment. Therefore, the control of this risk, characterized by dyslipidemia, hypertension, obesity, and insulin resistance, has become a major goal in many experimental and clinical studies in the context of CVD. In the present review, we summarized experimental studies and clinical trials of recent anti-diabetic and lipid-lowering therapies targeted to reduce CVD. Specifically, incretin-based therapies, sodium-glucose co-transporter 2 inhibitors, and proprotein convertase subtilisin kexin 9 inactivating therapies are described. Moreover, the novel molecular mechanisms explaining the CVD protection of the drugs reviewed here indicate major effects on vascular cells, inflammatory cells, and cardiomyocytes, beyond their expected anti-diabetic and lipid-lowering control. The revealed key mechanism is a prevention of acute cardiovascular events by restraining atherosclerosis at early stages, with decreased leukocyte adhesion, recruitment, and foam cell formation, and increased plaque stability and diminished necrotic core in advanced plaques. These emergent cardiometabolic therapies have a promising future to reduce CVD burden.

scholarly journals Regulation of Osteoclast Differentiation and Activity by Lipid Metabolism

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 89
Author(s):  
Haemin Kim ◽  
Brian Oh ◽  
Kyung-Hyun Park-Min
Keyword(s):  
Lipid Metabolism ◽  
Molecular Mechanisms ◽  
Bone Cells ◽  
Critical Role ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Metabolic Reprogramming ◽  
Lipid Lowering ◽  
Metabolic Bone Diseases ◽  
Increased Risk

Bone is a dynamic tissue and is constantly being remodeled by bone cells. Metabolic reprogramming plays a critical role in the activation of these bone cells and skeletal metabolism, which fulfills the energy demand for bone remodeling. Among various metabolic pathways, the importance of lipid metabolism in bone cells has long been appreciated. More recent studies also establish the link between bone loss and lipid-altering conditions—such as atherosclerotic vascular disease, hyperlipidemia, and obesity—and uncover the detrimental effect of fat accumulation on skeletal homeostasis and increased risk of fracture. Targeting lipid metabolism with statin, a lipid-lowering drug, has been shown to improve bone density and quality in metabolic bone diseases. However, the molecular mechanisms of lipid-mediated regulation in osteoclasts are not completely understood. Thus, a better understanding of lipid metabolism in osteoclasts can be used to harness bone cell activity to treat pathological bone disorders. This review summarizes the recent developments of the contribution of lipid metabolism to the function and phenotype of osteoclasts.

scholarly journals Biochemistry and Molecular Biology of Mechanisms of Action of Fibrates – An Overview

2019 ◽  
pp. 1-12 ◽  
Author(s):  
A.S. V. Prasad
Keyword(s):  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Organic Anion ◽  
Density Lipoprotein ◽  
The United States ◽  
Mechanisms Of Action ◽  
Lipid Lowering ◽  
Intervention Trial ◽  
Ligand Interaction ◽  
Cholesterol Acyl Transferase

Fibrates are a class of medication that mainly lowers the blood triglyceride levels. They reduce the LDL and increase the levels of HDL C, in the blood. Clofibrate, the first member to be discovered  in 1962 , and introduced in USA in 1967, is withdrawn in 2002, due to unexplained hepatomegaly, hepato-toxicity and possible risk of hepatic cancer. Other fibrates are introduced in the late 1970s and early 1980s, such as gemfibrozil in the United States and bezafibrate and ciprofibrate in Europe. Their lipid lowering effects are found to decrease CVS risk , progression of atherosclerosis and metabolic syndrome,  macrovascular and microvascular diabetic complications  like stroke, myocardial infarction, peripheral vascular disease  and  diabetic  retinopathy .Various clinical trials like VA-HIT trial (Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial) ,  FIELD trail.  (the Fenofibrate Intervention and Event Lowering in Diabetes) Helsinki Heart Study,   ACCORD -Lipid trial  (The lipid component of the Action to Control Cardiovascular Risk in Diabetes trial ) and  BIP (Bezafibrate Infarction Prevention Study)  trial and angiography trials, like LOCAT (Lopid Coronary Angiography Trial)  and BECLAIT (Bezafibrate Coronary Atherosclerosis Intervention Trial) demonstrated the  beneficial effects of gemfibrozil and fenofibrate.  Their mechanism of action remained obscure for three decades, ie till 1990s, when their mode of action was found. The Mechanism of action of fibrates include limitation of substrate availability for triglyceride synthesis in the liver, promotion of the action of lipoprotein lipase, (LPL)  modulation of low density lipoprotein receptor/ligand interaction and stimulation of reverse cholesterol transport The biochemical and molecular mechanisms involving  the various  enzymes like LCAT (Lecithin-cholesterol acyl transferase)  and CYP7A1 etc.  (cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) ) ,  transporters like ABC , CETP (ATP-binding cassette transporter, Cholesterol ester binding protein) and NTCP, OATP (Na+-dependent taurocholate transporter / organic anion transporters) . These are the.) and nuclear factors like LXR, PPAR alfa etc. (liver orphan receptor α , and peroxisome proliferative nuclear factor) , in relation to the mechanisms  of action of fibrates are discussed . Areas of current interests in literature are briefed.

scholarly journals Body mass index impacts the choice of lipid‐lowering treatment with no correlation to blood cholesterol – Findings from 52 916 patients in the Dyslipidemia International Study (DYSIS)

2018 ◽  
Vol 20 (11) ◽  
pp. 2670-2674 ◽  
Author(s):  
Jean Ferrières ◽  
Dominik Lautsch ◽  
Anselm K. Gitt ◽  
Gaetano De Ferrari ◽  
Hermann Toplak ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
International Study ◽  
Blood Cholesterol ◽  
Lipid Lowering

scholarly journals Stachys sieboldii Miq. Root Attenuates Weight Gain and Dyslipidemia in Rats on a High-Fat and High-Cholesterol Diet

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2063 ◽  
Author(s):  
Jennifer K. Lee ◽  
Jae-Joon Lee ◽  
Yeon-Kyoung Kim ◽  
Youngseung Lee ◽  
Jung-Heun Ha
Keyword(s):  
Adipose Tissue ◽  
Cholesterol Metabolism ◽  
Atherogenic Index ◽  
Lipid Lowering ◽  
Cardiac Risk Factor ◽  
Epididymal Adipose Tissue ◽  
High Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Stachys Sieboldii

This study aimed at investigating the anti-obesity and anti-dyslipidemic effects of Stachys sieboldii Miq. root (SS) powder in rats following a high-fat and high-cholesterol (HFC) diet for 6 weeks. Thirty-two Sprague–Dawley rats were fed one of the following diets: a regular diet (RD), HFC, HFC supplemented with 3% SS (HFC + 3SS) or HFC supplemented with 5% SS (HFC + 5SS). Following an HFC diet increased body weight (BW) gain (p < 0.001) and the food efficiency ratio (FER; p < 0.001); however, SS consumption gradually prevented the HFC-induced BW gain (p < 0.001) and increase in FER (p < 0.01). The HFC diet resulted in increased liver size (p < 0.001) and total adipose tissue weight (p < 0.001), whereas the SS supplementation decreased hepatomegaly (p < 0.05) and body fat mass (p < 0.001). SS consumption prevented the increased activities of serum alanine aminotransferase (ALT; p < 0.001), aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.01 in HFC + 5SS) and lactate dehydrogenase (LDH; p < 0.001 in HFC + 5SS) induced by the HFC diet (p < 0.001). The SS supplementation improved lipid profiles in the circulation by lowering triglyceride (TG; p < 0.01), total cholesterol (TC; p < 0.001) and non-HDL cholesterol (non-HDL-C; p < 0.001) levels, as well as the atherogenic index (p < 0.01) and cardiac risk factor (p < 0.01). The lipid distribution in the liver (p < 0.05) and white adipose tissues (WAT; p < 0.001) of the HFC + SS diet-consuming rats was remarkably lower than that of the HFC diet-consuming rats. The average size of the epididymal adipose tissue (p < 0.001) was significantly lower in the HFC + SS diet-fed rats than in the HFC diet-fed rats. The fecal lipid (>3% SS; p < 0.001) and cholesterol (5% SS; p < 0.001) efflux levels were significantly elevated by the SS supplementation compared to those measured in the RD or HFC diet-fed groups. In addition, the hepatic lipid and cholesterol metabolism-related gene expressions were affected by SS consumption, as the hepatic anabolic gene expression (Acc; p < 0.001, Fas; p < 0.001 and G6pdh; p < 0.01) was significantly attenuated. The HFC + 5SS diet-fed rats exhibited elevated hepatic Cyp7a1 (p < 0.001), Hmgcr (p < 0.001) and Ldlr (p < 0.001) mRNA expression levels compared to the HFC diet-fed rats. These results suggest that SS may possess anti-adipogenic and lipid-lowering effects by enhancing lipid and cholesterol efflux in mammals.

scholarly journals Effects on Liver Lipid Metabolism of the Naturally Occurring Dietary Flavone Luteolin-7-glucoside

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Carla Sá ◽  
Ana Rita Oliveira ◽  
Cátia Machado ◽  
Marisa Azevedo ◽  
Cristina Pereira-Wilson
Keyword(s):  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Regulatory Element ◽  
Lipid Lowering ◽  
Whole Body ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Hepatic Expression

Disruptions in whole-body lipid metabolism can lead to the onset of several pathologies such as nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs). The present study aimed at elucidating the molecular mechanisms behind the lipid-lowering effects of the flavone luteolin-7-glucoside (L7G) which we previously showed to improve plasma lipid profile in rats. L7G is abundant in plant foods of Mediterranean diet such as aromatic plants used as herbs. Results show that dietary supplementation with L7G for one week induced the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and of its target gene carnitine palmitoyl transferase 1 (CPT-1) in rat liver. L7G showed a tendency to decrease the hepatic expression of sterol regulatory element-binding protein-1 (SREBP-1), without affecting fatty acid synthase (FAS) protein levels. Although SREBP-2 and LDLr mRNA levels did not change, the expression of HMG CoA reductase (HMGCR) was significantly repressed by L7G. L7G also inhibited this enzyme’sin vitroactivity in a dose dependent manner, but only at high and not physiologically relevant concentrations. These results add new evidence that the flavone luteolin-7-glucoside may help in preventing metabolic diseases and clarify the mechanisms underlying the beneficial health effects of diets rich in fruits and vegetables.

A Comparative Study of Embelia Schiperi and Embelia Keniensis on Blood Glucose and Triglycerides in Normal and Epinephrine- Induced Hyperglycemic Mice

1999 ◽  
Vol 27 (03n04) ◽  
pp. 365-370
Author(s):  
Atsushi Kato ◽  
Toshihiro Miura ◽  
Yumi Nishiyama ◽  
Yoko Tachibana ◽  
Yasuhiro Ohnishi ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Comparative Study ◽  
Methanol Extract ◽  
Intraperitoneal Administration ◽  
The Other ◽  
Blood Cholesterol ◽  
Lipid Lowering ◽  
Other Hand ◽  
Lowering Activity

Intraperitoneal administration of the methanol extract of Embelia schiperi (ES) to normal mice caused a significant decrease in blood glucose (p < 0.01) and a significant increase in triglycerides 4 hours after administration at 100 mg/kg (p < 0.01). The toluene fraction of Embelia keniensis methanol extract (TS) showed hypoglycemic and lipid lowering activity 7 hours after intraperitoneal administration at 100 mg/kg. In addition, TS (100 mg/kg) administration significantly decreased blood glucose in epinephrine-induced hyperglycemic mice (p < 0.01). Moreover, ES tended to increase while TS tended to decrease the blood triglycerides in epinephrine-induced hyperglycemic mice. On the other hand, no changes in blood cholesterol were observed after the administration of ES or TS in normal and epinephrine-induced hyperglycemic mice. We found that two species from Embelia, ES and TS, have different activities on blood glucose and triglycerides in normal and epinephrine-induced hyperglycemic mice.

Effects of сramizol on expression of the ApoA1 gene in rats with experimental hyperlipidemia

2019 ◽  
Vol 65 (5) ◽  
pp. 403-406
Author(s):  
A.V. Lizunov ◽  
I.V. Okunevich ◽  
S.V. Orlov ◽  
A.A. Lebedev ◽  
E.R. Bychkov ◽  
...  
Keyword(s):  
Normal Values ◽  
Atherogenic Index ◽  
Lipid Lowering ◽  
Blood Levels ◽  
Hypolipidemic Agents ◽  
Apoa1 Gene ◽  
Lipid Lowering Drug ◽  
Experimental Hyperlipidemia ◽  
Triton Wr 1339 ◽  
Lowering Drug

An imidazole derivative cramizol, has lipid-lowering and anti-atherogenic effects. Cramizol reduces blood levels of cholesterol and triglycerides, and also reduces the atherogenic index in animals with acute hyperlipidemia induced by Triton WR-1339. Cramizol and the lipid-lowering drug fenofibrate exhibited similar effectiveness as hypolipidemic agents. Cramizol also restores the expression of the Apoa1 gene in rats with experimentally induced hyperlipidemia to normal values. This may be a basis of its hypolipidemic and anti-atherogenic action.

Obesity and metabolic syndrome in Brazilian patients with bipolar disorder

2009 ◽  
Vol 21 (2) ◽  
pp. 84-88 ◽  
Author(s):  
Karla Mathias de Almeida ◽  
Márcia B. de Macedo-Soares ◽  
Cilly Kluger Issler ◽  
José Antonio Amaral ◽  
Sheila C. Caetano ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Bipolar Disorder ◽  
General Population ◽  
Medication Use ◽  
Density Lipoprotein ◽  
Heart Association ◽  
Blood Cholesterol ◽  
Lipid Lowering ◽  
High Fasting Glucose ◽  
Prevalence Of Obesity

Objective:We aimed to determine the prevalence of obesity and metabolic syndrome (O/MetS) in a sample of Brazilian outpatients with bipolar disorder.Methods:Eighty-four patients with bipolar disorder were evaluated. We used the definition of MetS established in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, modified by the American Heart Association (AHA). Patients were classified as obese if their body mass index (BMI) was ≥ 30 kg/m2.Results:We found that 28.6% of our sample met the AHA criteria for MetS and 35.7% were obese. The percentage of patients meeting each criterion of the AHA was as follows: 46% for abdominal obesity; 44% for hypertriglyceridemia or cholesterol-lowering medication use; 26% for low high-density lipoprotein cholesterol or being on a lipid-lowering medication; 45% for hypertension; and 20% for high fasting glucose or anti-diabetic medication use.Conclusions:The prevalence of obesity in our sample of outpatients with bipolar disorder was higher than that observed for the general population of Brazil. The rate of MetS was similar to that observed for the general population. Our data indicate the need for prevention, early detection and treatment of O/MetS in patients with bipolar disorder.

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