scholarly journals Features of Lipid Metabolism in Humanized ApoE Knockin Rat Models

2021 ◽  
Vol 22 (15) ◽  
pp. 8262
Author(s):  
Yang Wu ◽  
Gem Johnson ◽  
Fujie Zhao ◽  
Yin Wu ◽  
Guojun Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Low Density Lipoprotein ◽  
Susceptibility Gene ◽  
Pulmonary Arteries ◽  
Density Lipoprotein ◽  
Premature Death ◽  
Wall Thickening ◽  
Atherosclerotic Lesions ◽  
Short Period ◽  
Apoe Ko

Apolipoprotein E (ApoE), an essential plasma apolipoprotein, has three isoforms (E2, E3, and E4) in humans. E2 is associated with type III hyperlipoproteinemia. E4 is the major susceptibility gene to Alzheimer’s disease (AD) and coronary heart disease (CHD). We investigated lipid metabolism and atherosclerotic lesions of novel humanized ApoE knockin (hApoE KI) rats in comparison to wide-type (WT) and ApoE knockout (ApoE KO) rats. The hApoE2 rats showed the lowest bodyweight and white fat mass. hApoE2 rats developed higher serum total cholesterol (TC), total triglyceride (TG), and low- and very low density lipoprotein (LDL-C&VLDL-C). ApoE KO rats also exhibited elevated TC and LDL-C&VLDL-C. Only mild atherosclerotic lesions were detected in hApoE2 and ApoE KO aortic roots. Half of the hApoE2 rats developed hepatic nodular cirrhosis. A short period of the Paigen diet (PD) treatment led to the premature death of the hApoE2 and ApoE KO rats. Severe vascular wall thickening of the coronary and pulmonary arteries was observed in 4-month PD-treated hApoE4 rats. In conclusion, hApoE2 rats develop spontaneous hyperlipidemia and might be suitable for studies of lipid metabolism-related diseases. With the PD challenge, hApoE4 KI rats could be a novel model for the analysis of vascular remodeling.

scholarly journals Differences in the Effects of Anthocyanin Supplementation on Glucose and Lipid Metabolism According to the Structure of the Main Anthocyanin: A Meta-Analysis of Randomized Controlled Trials

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2003
Author(s):  
Risa Araki ◽  
Akira Yada ◽  
Hirotsugu Ueda ◽  
Kenichi Tominaga ◽  
Hiroko Isoda
Keyword(s):  
Lipid Metabolism ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Resistance Index ◽  
Lipoprotein Cholesterol ◽  
Controlled Trials ◽  
Oh Groups ◽  
Chemical Structures ◽  
Glucose And Lipid Metabolism

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): −0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: −0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.

scholarly journals The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bushra Yusuf ◽  
Ilya Mukovozov ◽  
Sajedabanu Patel ◽  
Yi-Wei Huang ◽  
Guang Ying Liu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Super Resolution ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Cortical Actin ◽  
Cytoskeletal Remodeling ◽  
Atherosclerotic Lesions ◽  
Modified Lipoproteins

AbstractAtherosclerosis is characterized by retention of modified lipoproteins, especially oxidized low density lipoprotein (oxLDL) within the sub-endothelial space of affected blood vessels. Recruited monocyte-derived and tissue-resident macrophages subsequently ingest oxLDL by binding and internalizing oxLDL via scavenger receptors, particularly CD36. The secreted neurorepellent, Slit2, acting through its transmembrane receptor, Roundabout-1 (Robo-1), was previously shown to inhibit recruitment of monocytes into nascent atherosclerotic lesions. The effects of Slit2 on oxLDL uptake by macrophages have not been explored. We report here that Slit2 inhibits uptake of oxLDL by human and murine macrophages, and the resulting formation of foam cells, in a Rac1-dependent and CD36-dependent manner. Exposure of macrophages to Slit2 prevented binding of oxLDL to the surface of cells. Using super-resolution microscopy, we observed that exposure of macrophages to Slit2 induced profound cytoskeletal remodeling with formation of a thick ring of cortical actin within which clusters of CD36 could not aggregate, thereby attenuating binding of oxLDL to the surface of cells. By inhibiting recruitment of monocytes into early atherosclerotic lesions, and the subsequent binding and internalization of oxLDL by macrophages, Slit2 could represent a potent new tool to combat individual steps that collectively result in progression of atherosclerosis.

Emodin alleviated hyperlipidemia and hepatic lipid metabolism in zebrafish larvae fed a high-cholesterol diet via AMPK/SREBP-2/PCSK9/LDLR signaling pathway

2021 ◽  
Author(s):  
Linfeng He ◽  
Cheng Wang ◽  
Yafang Zhang ◽  
Chaocheng Guo ◽  
Yan Wan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Cholesterol Diet ◽  
Low Density ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Cholesterol Accumulation ◽  
Hepatic Lipid ◽  
Zebrafish Larvae

Abstract BackgroundEmodin (EM) is one of bioactive components extracted from Rheum palmatum L. (Dahuang), which possesses numerous pharmacological activities including hypolipidemic effect. However, the potential action of EM on hyperlipidemia (HLP) remains unclear. Here, the theraputic effect of EM against HLP were investigated.MethodsIn this study, the hypolipidemic properties of EM were evaluated using high-cholesterol diet (HCD)-stimulated zebrafish larvae model. The body weight, body length and body mass index (BMI) was measured. The total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) as well as the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by corresponding assay kits. Tg (flil: eGFP) zebrafish were utilized to observe vascular cholesterol accumulation and Tg (mpx: eGFP) zebrafish to visualize and quantify neutrophil inflammation. The hepatic lipid deposition and hepatic histopathology were analyzed by Oil red O staining and H&E staining, respectively. Finally, the underlying mechanism of EM were investigated using real-time quantitative PCR (RT-qPCR) analysis to assess the gene levels of adenosine monophosphate-activated protein kinase alpha (AMPKα), sterol regulatory element binding protein 2 (SREBP-2), proprotein convertase subtilisin kexin 9 (PCSK9), low-density lipoprotein receptor (LDLR), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), adenosine triphosphate binding cassette transporter A1 (ABCA1) and adenosine triphosphate binding cassette transporter G1 (ABCG1).ResultsOur data indicated that EM reduced obesity of zebrafish as evidenced by the decrease in body weight, body length and BMI. EM significantly reduced TC, TG, and LDL-C, and increased HDL-C contents. Moreover, it displayed a prominent inhibitory effect on blood cholesterol accumulation, hepatic lipid accumulation, and neutrophil inflammation in vascular site. Additionally, EM improved the liver function through decreasing ALT and AST levels of zebrafish with HCD-induced hepatosteatosis. Further investigation showed that EM treatment attenuated lipid accumulation via upregulating the expression of AMPKα, LDLR, ABCA1 and ABCG1, and downregulating the expression of SREBP-2, PCSK9 and HMGCR.ConclusionTo conclude, EM alleviated lipid metabolism disorder symptoms caused by HCD via modulating AMPK/SREBP-2/PCSK9/LDLR pathway in larvae, suggesting that EM may be developed into hypolipidmic agent for treating lipid metabolism related diseases.

scholarly journals Regulation of very-low-density-lipoprotein lipid secretion in hepatocyte cultures derived from diabetic animals

1989 ◽  
Vol 262 (1) ◽  
pp. 313-319 ◽  
Author(s):  
J M Duerden ◽  
S M Bartlett ◽  
G F Gibbons
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Whole Body ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Short Period ◽  
Streptozotocin Diabetic Rats ◽  
Cholesterol Secretion

Hepatocytes were derived from 2-3-day streptozotocin-diabetic rats and maintained in culture for up to 3 days. Compared with similar cultures from normal animals, these hepatocytes secreted less very-low-density-lipoprotein (VLDL) triacylglycerol, but the decrease in the secretion of VLDL non-esterified and esterified cholesterol was not so pronounced. This resulted in the secretion of relatively cholesterol-rich VLDL particles by the diabetic hepatocytes. Addition of insulin for a relatively short period (24 h) further decreased the low rates of VLDL triacylglycerol secretion from the diabetic hepatocytes. The secretion of VLDL esterified and non-esterified cholesterol also declined. These changes occurred irrespective of whether or not exogenous fatty acids were present in the culture medium. Little or no inhibitory effect of insulin was observed after longer-term (24-48 h) exposure to the hormone. Both dexamethasone and a mixture of lipogenic precursors (lactate plus pyruvate) stimulated VLDL triacylglycerol and cholesterol secretion, but not to the levels observed in hepatocytes from normal animals. The low rate of hepatic VLDL secretion in diabetes contrasts with the increase in whole-body VLDL production rate. This suggests that the intestine is a major source of plasma VLDL in insulin-deficient diabetes.

scholarly journals Pro-atherogenic lipid profile in pulmonary tuberculosis patients with concurrent insulin resistance

2021 ◽  
Vol 8 (2) ◽  
pp. 111-114
Author(s):  
Olga Shvets ◽  
Olga Shevchenko ◽  
Zoriana Piskur ◽  
Hanna Stepanenko ◽  
Olha Pohorielova
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Pulmonary Tuberculosis ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Tuberculosis Patients ◽  
Group 2 ◽  
Group 1

Background. The problem of studying lipid metabolism in patients with tuberculosis is of interest to scientists around the world. The purpose of the study - to investigate lipid profile in pulmonary tuberculosis patients with concurrent insulin resistance. Materials and methods. Forty-one patients with pulmonary tuberculosis were examined. Insulin resistance index (HOMA-IR), total cholesterol level (TC), triglycerides (TG) level, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol and atherogenic index (AI) were measured. Results. Group 1 - 26 patients with tuberculosis and insulin resistance (HOMA-IR ˃ 2.7); Group 2 – 15 patients with tuberculosis without insulin resistance (HOMA-IR ˂ 2.7). Group 1 patients had severe course of TB with fever, severe fatigue and weakness, profuse sweating, weight loss, cough and shortness of breath. Median TC indices differed at significant level (p = 0.012): group 1 - 4.82 mmol/l, group 2 - 4.25 mmol/l. TG level was higher in group 1 patients - 1.32 mmol/l than in group 2 patients - 1.28 mmol/l. LDL cholesterol values were higher in group 1 patients - 3.2 mmol/l vs 2.5 mmol/l in group 2. The AI was higher in group1 (p = 0.005): 3.9 units against 2.8 units in group 2 patients. Conclusions. Insulin resistance in pulmonary tuberculosis patients was associated with severe course of the disease, severe clinical manifestations and impaired external respiration. Pro-atherogenic disorders of lipid metabolism in pulmonary tuberculosis patients with concurrent insulin resistance can be considered as the degree of endogenous intoxication.

Pharmacological Management of Dyslipidemia in Atherosclerosis: Limitations, Challenges, and New Therapeutic Opportunities

Angiology ◽  
2018 ◽  
Vol 70 (3) ◽  
pp. 197-209 ◽  
Author(s):  
Kyriakos E. Kypreos ◽  
Rafael Bitzur ◽  
Eleni A. Karavia ◽  
Eva Xepapadaki ◽  
George Panayiotakopoulos ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Lipoprotein Cholesterol ◽  
Residual Cardiovascular Risk ◽  
Pharmacological Management ◽  
Therapeutic Modalities ◽  
Atherosclerotic Lesions ◽  
Low Levels

Clinical and epidemiological studies during the last 7 decades indicated that elevated low-density lipoprotein cholesterol (LDL-C) levels and reduced high-density lipoprotein cholesterol (HDL-C) levels correlate with the pathogenesis and progression of atherosclerotic lesions in the arterial wall. This observation led to the development of LDL-C-lowering drugs for the prevention and treatment of atherosclerosis, some with greater success than others. However, a body of recent clinical evidence shows that a substantial residual cardiovascular risk exists even at very low levels of LDL-C, suggesting that new therapeutic modalities are still needed for reduction of atherosclerosis morbidity and mortality. Unfortunately, HDL-C-raising drugs developed toward this goal had disappointing results thus far. Here, we critically review the literature presenting available evidence and challenges that need to be met and discuss possible new avenues for the development of novel lipid pharmacotherapeutics to reduce the burden of atherosclerosis.

Influence of Melatonin and Linseed Oil on the State of Lipid Metabolism at Desynchronosis in Rats

2021 ◽  
pp. 58-68
Author(s):  
Irina S. Sobolevskaya ◽  
◽  
Oleg D. Myadelets ◽  
Natalʼya N. Yarotskaya
Keyword(s):  
Lipid Metabolism ◽  
Linseed Oil ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherogenic Index ◽  
Male Rats ◽  
Serum Concentrations ◽  
Rat Serum ◽  
Lighting Conditions

The purpose of this study was to substantiate the possibility of correcting lipid metabolism changes at dark deprivation using linseed oil, melatonin, and their combination. Materials and methods. The experiment involved 130 white outbred male rats with a body weight of 170–220 g. The animals were divided into 5 groups: rats under standard fixed lighting conditions (12 hours light/12 hours dark); rats under modelled dark deprivation with round-the-clock lighting (24 hours light); rats under modelled dark deprivation with round-the-clock lighting (24 hours light) receiving intragastric injections of linseed oil, melatonin or their combination from day 1 of the experiment. Serum concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total phospholipids (TPL) and atherogenic index (AI) were determined. Results. Long-term dark deprivation led to dyslipoproteinemia, which consists in an increase in serum concentrations of TC by a factor of 1.33 (p = 0.0009), TG by a factor of 1.62 (p = 0.013), LDL-C by a factor of 1.2 (p = 0.026) and TPL by a factor of 1.15 (p = 0.0082). The severity of changes in TC, TG, LDL-C, HDL-C and TPL concentrations varied depending on the duration of the experiment. During the use of linseed oil, melatonin or their combination under dark deprivation, the severity of disorders caused by desynchronosis decreased and lipid metabolism in rat serum normalized, especially at the initial stages of the research. Conclusion. Changes in lipid metabolism due to desynchronosis in rats injected with the substances under study were significantly smaller compared with animals that did not receive them. The most pronounced effects of administering these substances were observed in the group of rats treated with linseed oil and melatonin at the same time.

scholarly journals ChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue

2020 ◽  
Vol 11 ◽  
Author(s):  
Katsumi Iizuka ◽  
Ken Takao ◽  
Daisuke Yabe
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Whole Body ◽  
Acetyl Coa ◽  
Alcoholic Fatty Liver

Carbohydrate response element-binding protein (ChREBP) plays an important role in the development of type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, as well as tumorigenesis. ChREBP is highly expressed in lipogenic organs, such as liver, intestine, and adipose tissue, in which it regulates the production of acetyl CoA from glucose by inducing Pklr and Acyl expression. It has recently been demonstrated that ChREBP plays a role in the conversion of gut microbiota-derived acetate to acetyl CoA by activating its target gene, Acss2, in the liver. ChREBP regulates fatty acid synthesis, elongation, and desaturation by inducing Acc1 and Fasn, elongation of long-chain fatty acids family member 6 (encoded by Elovl6), and Scd1 expression, respectively. ChREBP also regulates the formation of very low-density lipoprotein by inducing the expression of Mtp. Furthermore, it plays a crucial role in peripheral lipid metabolism by inducing Fgf21 expression, as well as that of Angptl3 and Angptl8, which are known to reduce peripheral lipoprotein lipase activity. In addition, ChREBP is involved in the production of palmitic-acid-5-hydroxystearic-acid, which increases insulin sensitivity in adipose tissue. Curiously, ChREBP is indirectly involved in fatty acid β-oxidation and subsequent ketogenesis. Thus, ChREBP regulates whole-body lipid metabolism by controlling the transcription of lipogenic enzymes and liver-derived cytokines.

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