Triglyceride and Triglyceride-Rich Lipoproteins in Atherosclerosis

Zhang, Baihui; Yin, Fang‐Fang; Qiao, Yanan; Guo, Shoudong

doi:10.3389/fmolb.2022.909151

Cited by 20 publications

(20 citation statements)

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“…To investigate the underlying mechanisms, real-time quantitative polymerase chain reaction (RT-qPCR) and Western Blotting experiments were used for determining the expression of lipid metabolism-related genes and proteins, respectively. As accumulating evidence have demonstrated that gut microbiota may modulate obesity ( 10 , 23 ), the effect of fenofibrate on gut microbiota in ob/ob mice was also analyzed in the present study.…”

Section: Methodsmentioning

confidence: 99%

“…For instance, TG accumulation in the liver is defined as fatty liver diseases including NALFD and non-alcoholic steatohepatitis, which currently have no approved drugs for therapy ( 8 , 9 ). Furthermore, TG is a residual risk factor of CVD ( 10 ). Theoretically, drugs with TG-lowering activity have a potential application for treatment of TG accumulation.…”

Section: Introductionmentioning

confidence: 99%

“…Mechanistically, fenofibrate can enhance the expression of the enzymes involved in fatty acid (FA) β-oxidation including acyl-CoA oxidase (ACOX) and liver X receptor in C57BL/6J mice and humans ( 14 , 16 , 17 ). However, fenofibrate shows limited beneficial effects on therapy of CVD ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

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Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet

et al. 2022

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Obesity is characterized by lipid accumulation in distinct organs. Presently, fenofibrate is a commonly used triglyceride-lowering drug. This study is designed to investigate whether long-term fenofibrate intervention can attenuate lipid accumulation in ob/ob mouse, a typical model of obesity. Our data demonstrated that fenofibrate intervention significantly decreased plasma triglyceride level by 21.0%, increased liver index and hepatic triglyceride content by 31.7 and 52.1%, respectively, and elevated adipose index by 44.6% compared to the vehicle group. As a PPARα agonist, fenofibrate intervention significantly increased the expression of PPARα protein in the liver by 46.3% and enhanced the expression of LDLR protein by 3.7-fold. However, fenofibrate dramatically increased the expression of PPARγ and SREBP-1c proteins by ~2.1- and 0.9-fold in the liver, respectively. Fenofibrate showed no effects on the expression of genes-related to fatty acid β-oxidation. Of note, it significantly increased the gene expression of FAS and SCD-1. Furthermore, fenofibrate modulated the gut microbiota. Collectively, long-term fenofibrate induces lipid accumulation in liver and adipose tissues in ob/ob mice by enhancing the expression of adipogenesis-related proteins and gut microbiota. These data suggest that fenofibrate may have limited effects on attenuating lipid deposition in obese patients.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet

et al. 2022

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“…Furthermore, the elevated plasma levels of sdLDL are generally accompanied with reduced levels of HDL-C and Apo A-I, and elevated levels of TG and ApoB. It has been well-documented that HDL and Apo A-I are atheroprotective, while TG- and ApoB-containing lipoproteins are atherogenic ( Diffenderfer and Schaefer, 2014 ; Zhang et al, 2022 ).…”

Section: Atherogenic Mechanisms Of Ldlmentioning

confidence: 99%

“…However, PCSK9i show attractive lipid-lowering and anti-atherosclerotic effects in practice ( Cannon et al, 2015 ; Chaudhary et al, 2017 ; Guo et al, 2020 ). As we reviewed recently, angiopoietin-like protein (ANGPTL), such as ANGPTL3, plays a key in regulation of both cholesterol and TG via inhibition of LPL ( Zhang et al, 2022 ). The antisense oligonucleotide of ANGPTL3 has been applied to familial hypercholesterolemia and is now in phase 3 clinical trial ( Graham et al, 2017 ).…”

Section: Therapies Targeting Ldl-pmentioning

confidence: 99%

Low-density lipoprotein particles in atherosclerosis

2022

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Among the diseases causing human death, cardiovascular disease (CVD) remains number one according to the World Health Organization report in 2021. It is known that atherosclerosis is the pathological basis of CVD. Low-density lipoprotein (LDL) plays a pivotal role in the initiation and progression of atherosclerotic CVD (ASCVD). LDL cholesterol (LDL-C) is the traditional biological marker of LDL. However, large numbers of patients who have achieved the recommended LDL-C goals still have ASCVD risk. In multiple prospective studies, LDL particle (LDL-P) is reported to be more accurate in predicting CVD risk than LDL-C. LDL-Ps differ in size, density and chemical composition. Numerous clinical studies have proved that the atherogenic mechanisms of LDL-Ps are determined not only by LDL number and size but also by LDL modifications. Of note, small dense LDL (sdLDL) particles possess stronger atherogenic ability compared with large and intermediate LDL subfractions. Besides, oxidized LDL (ox-LDL) is another risk factor in atherosclerosis. Among the traditional lipid-lowering drugs, statins induce dramatic reductions in LDL-C and LDL-P to a lesser extend. Recently, proprotein convertase subtilsin/kexin type 9 inhibitors (PCSK9i) have been demonstrated to be effective in lowering the levels of LDL-C, LDL-P, as well as CVD events. In this article, we will make a short review of LDL metabolism, discuss the discordance between LDL-C and LDL-P, outline the atherogenic mechanisms of action of LDL by focusing on sdLDL and ox-LDL, summarize the methods used for measurement of LDL subclasses, and conclude the advances in LDL-lowering therapies using statins and PCSK9i.

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Increased Plasma Levels of Triglyceride-Enriched Lipoproteins Associate with Systemic Inflammation, Lipopolysaccharides, and Gut Dysbiosis in Common Variable Immunodeficiency

et al. 2023

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Purpose Triglycerides (TG) and their major transport lipoprotein in the circulation (VLDL) appear to be related to inflammation. Patients with common variable immunodeficiency (CVID) have inflammatory complications associated with gut microbial dysbiosis. We hypothesized that CVID patients have disturbed TG/VLDL profiles associated with these clinical characteristics. Methods We measured plasma concentrations of TGs, inflammatory markers, and lipopolysaccharide (LPS) in 95 CVID patients and 28 healthy controls. Additionally, in 40 CVID patients, we explored plasma lipoprotein profiling, fatty acid, gut microbial dysbiosis, and diet. Results TG levels were increased in CVID patients as compared to healthy controls (1.36 ± 0.53 mmol/l versus 1.08 ± 0.56 [mean, SD], respectively, P = 0.008), particularly in the clinical subgroup “Complications,” characterized by autoimmunity and organ-specific inflammation, compared to “Infection only” (1.41 mmol/l, 0.71[median, IQR] versus [1.02 mmol/l, 0.50], P = 0.021). Lipoprotein profile analyses showed increased levels of all sizes of VLDL particles in CVID patients compared to controls. TG levels correlated positively with CRP (rho = 0.256, P = 0.015), IL-6 (rho = 0.237, P = 0.021), IL-12 (rho = 0.265, P = 0.009), LPS (r = 0.654, P = 6.59 × 10−13), CVID-specific gut dysbiosis index (r = 0.315, P = 0.048), and inversely with a favorable fatty acid profile (docosahexaenoic acid [rho = − 0.369, P = 0.021] and linoleic acid [rho = − 0.375, P = 0.019]). TGs and VLDL lipids did not appear to be associated with diet and there were no differences in body mass index (BMI) between CVID patients and controls. Conclusion We found increased plasma levels of TGs and all sizes of VLDL particles, which were associated with systemic inflammation, LPS, and gut dysbiosis in CVID, but not diet or BMI.

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Triglyceride and Triglyceride-Rich Lipoproteins in Atherosclerosis

Cited by 20 publications

References 281 publications

Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet

Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet

Low-density lipoprotein particles in atherosclerosis

Increased Plasma Levels of Triglyceride-Enriched Lipoproteins Associate with Systemic Inflammation, Lipopolysaccharides, and Gut Dysbiosis in Common Variable Immunodeficiency

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