IBL News

1) Dr. Mitsuyo Okazaki,
*Professor emeritus of Tokyo Medical and Dental University.
*Fellow of the Japan Oil Chemists' Society.
*LipoSEARCH® Senior Technical Advisor of Immuno-Biological Laboratories Co.,Ltd.

LipoSEARCH🄬 Analysis Principles and Data Items

LipoSEARCH🄬 Features and Benefits

• Only a small amount of serum/plasma is required.
      (Human: 45µL, Animals: 35µL)
      Low-concentration samples such as culture supernatant and CSF
      can be analyzed.
• No sample pretreatment is required.
• Any animal species of sample is acceptable.
      Various results including humans, mice, rabbits, monkeys,
      cows, parrots, lizards, medaka (Oryzias latipes), etc.
• Provide detailed lipoprotein profiling data.
      4 major classes (CM, VLDL, LDL and HDL) and 20 subclasses can be analyzed.
      The size and quantity of particles such as HDL and LDL can also be analyzed.
• The effects of developing drugs on lipoprotein fractions can be evaluated.

LipoSEARCH® Application

Lipoprotein analysis by GP-HPLC and NMR
in pemafibrate phase 2 study (Human)

The study compared GP-HPLC (LipoSEARCH🄬) and NMR method for measuring lipoprotein particle numbers (PNs) of 212 dyslipidemia patients who were given pemafibrate (selective PPARα Modulator) in phase II clinical study. The PNs of major lipoprotein classes of total CM&VLDL, total LDL and total HDL in dyslipidemic patients analyzed by GP-HPLC correlated positively with NMR. However, the PNs of lipoprotein subclasses differed between two methods. It is concluded GP-HPLC (LipoSEARCH🄬) accurately measures the lipoprotein PNs than NMR and can be used for assessing the effects of lipid-lowering drugs on lipoprotein subclasses.
Distinct Differences in Lipoprotein Particle Number Evaluation between GP-HPLC and NMR: Analysis in Dyslipidemic Patients Administered a Selective PPARα Modulator, Pemafibrate. Yamashita S et al. J Atheroscler Thromb. 2021 Sep 1;28(9):974-996.

Relationship between the lipoprotein subclasses and cIMT (Human)

In this study, cholesterol and triglyceride content of 20 lipoprotein subclasses were analyzed using GP-HPLC (LipoSEARCH®) in 864 Japanese, both sexes (average age 57 years, free from chronic liver or kidney diseases, and no medication of lipid-lowering, hormone replacement, or adrenocorticosteroid). Univariate and multivariate regression analyses, and univariate and partial correlation analyses were performed to evaluate the relation between lipoprotein subclasses and maximum carotid intima-media thickness (cIMT) levels. Elevated small and medium LDL-C were correlated with higher maximum cIMT levels in both sexes (all p for trend < 0.05). The results endorse the theory that cholesterol in small and medium LDL is a significant risk factor of atherosclerotic disease.
Relationship between the cholesterol and triglyceride content of lipoprotein subclasses and carotid intima-media thickness: A cross-sectional population-based study. Ikezaki H et al. Clin Chim Acta. 2023 Aug 17;548:117521.

Anti-ANGPTL3 peptide vaccine for dyslipidemia and associated diseases (Mice)

In this study, a peptide vaccine, targeted 10 amino acid from ANGPTL 3 sequences was generated, and administered into dyslipidemia and related diseases model mice. The results demonstrated that ANGPTL3 peptide vaccine improved obesity-induced dyslipidemia, fatty liver, and dyslipidemia and atherosclerosis in familial hypercholesterolemia. The vaccine effect was confirmed after 30th weeks measurement, and no major cytotoxic autoimmune responses observed in the mice. It has concluded that the ANGPTL3 peptide vaccine could be an effective therapeutic strategy against dyslipidemia and associated diseases.
Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia. Fukami H et al. Cell Rep Med. 2021 Nov 16;2(11):100446.

Cholesterol-lowering effect of exendin-4 (GLP-1 receptor agonist) (Mice)

In this study, exendin-4 was administered to Ldlr−/− and C57BL/6J mice for 5 days, and evaluated serum lipoprotein profiles, cholesterol metabolism-related gene expression, and protein levels. The results demonstrated that exendin-4 treatment significantly decreased VLDL-C, LDL-C and mature hepatic SREBP2 and increased hepatic Insig1/2 mRNA expression in both mouse strains. In Ldlr−/− mice, exendin-4 treatment also significantly decreased hepatic cholesterol and fecal BA excretion, decreased hepatic Cyp7a1 mRNA expression, and increased small intestinal Fgf15 mRNA expression. In C57BL/6J mice, exendin-4 treatment significantly decreased small intestinal NPC1L1. Those results indicate that exendin-4 regulates serum Cholesterol independently of LDL and may reduce cholesterol absorption by different mechanisms in both mouse strains. It has concluded that GLP-1 receptor agonists may be reasonable therapeutic options for type 2 diabetes mellitus patients and familial hypercholesterolemia with defective LDL receptor activity.
Acute Cholesterol-Lowering Effect of Exendin-4 in Ldlr-/- and C57BL/6J Mice. Hori M et al. J Atheroscler Thromb. 2023 Jan 1;30(1):74-86.