Kaempferol ameliorates symptoms of metabolic syndrome by improving blood lipid profile and glucose tolerance

Kaempferol (KPF) is a dietary polyphenol reported to have various beneficial effects on human health. However, its molecular mechanisms in regulating lipid and glucose metabolism are not fully understood. This study examined the effects of KPF on obesity, dyslipidemia, and diabetes in Tsumura, Suzuki, Obese Diabetes (TSOD) mice. The six-week administration of KPF decreased fat weight, serum total cholesterol, and low-density lipoproteins (LDLs); increased high-density lipoproteins (HDLs); and improved glucose tolerance. Additionally, KPF increased LDL receptor (LDLR) and apolipoprotein A1 (ApoA1) gene expression and decreased serum resistin levels. These findings suggest that the decrease in LDL and the increase in HDL caused by KPF may be due to increases in hepatic LDLR and ApoA1 expression, respectively. Furthermore, it is possible that the improvement in glucose tolerance by KPF may occur via resistin reduction. These mechanisms may be parts of complex mechanism by which KPF improves metabolic syndrome.

Lipid Profile of Plasma in Young Women Depending on Their Physical Activity and Hereditary Predisposition

We studied the association of the polymorphic rs320 variant of the lipoprotein lipase (LPL) gene, rs2016520 variant of the peroxisome proliferator-activated receptor delta (PPARD) gene and rs670 variant of the apolipoprotein A1 (APOA1) gene with blood lipids in female athletes and women not involved in sports. Key indicators of the lipid spectrum – total cholesterol (TC), triglycerides (TG), highdensity lipoproteins (HDL) and low-density lipoproteins (LDL) in the blood serum – were determined by the enzymatic method using Cormay reagents (Germany) and Fluorat-02-ABLF-T analyser (Russia). Genotyping of the samples was carried out by means of the PCR-RFLP analysis. A direct correlation was found between the *H+ allele of the rs320 polymorphic variant of the LPL gene and the blood levels of TC (r = 0.17; p = 0.01), TG (r = 0.33; p = 0.000005), LDL (r = 0.16; p = 0.02), and atherogenic index (AI) (r = 0.28; p = 0.0002), as well as an inverse correlation between this allele and HDL (r = –0.19; p = 0.009) in women not involved in sports. The *A allele of the polymorphic variant rs670 of the APOA1 gene in this group showed a negative correlation with TC (r = –0.22; p = 0.004) and TG (r = –0.31; p = 0.00004), while the polymorphic variant rs2016520 of the PPARD gene revealed a linear correlation of the *C allele with LDL (r = 0.15; p = 0.02) and AI (r = 0.16; p = 0.01). Three alleles – *H of the LPL gene, *G of the APOA1 gene and *T of the PPARD gene – demonstrated an additive effect on the decrease in TG, LDL and AI and on the increase in HDL in women regardless of their level of motor activity. There were no statistically significant differences in the level of blood lipids in female athletes with different genotypes of the LPL, PPARD, and APOA1 genes. Further research is needed involving larger samples of athletes.

The Association of Apolipoprotein A1 Gene Polymorphisms with Acute Lymphocytic Leukemia in Tehran Province

Background: Acute lymphocytic leukemia (ALL) is a cancer of the lymphoid line of blood cells. It is characterized by the development of large numbers of immature lymphocytes. It is one of the most common cancers among children. Molecular markers can play an important role in determining the nature of leukemia-related tumors and can be used as a diagnostic adjuvant along with precise pathological methods. Some research has shown that apolipoprotein A1 gene polymorphisms were associated with the formation of various types of diseases. Objectives: This study aimed to evaluate the association of ApoA1 gene insertion/deletion polymorphisms with ALL disease. Methods: The salting-out method was used for DNA extraction from the blood samples. Questionnaires were prepared with the approval of a demographic data expert. The genotype distribution and allele frequencies for the ApoA1 gene insertion/deletion polymorphisms were determined by Gap-polymerase chain reaction (Gap-PCR) to compare patient’s cases with ALL disease and healthy subjects. This case-control study was performed by odds ratio (OR, with a confidence interval of 0.95) to reveal the association of these polymorphisms with ALL disease. Results: In this study, two ApoA1 gene polymorphisms, including II and DD genotypes, were observed, which II genotype had the highest frequency in both groups of healthy subjects and patients. However, no significant differences were found between the two groups (P > 0.05). ALL and both genotypes had a higher frequency in males than females. Despite the high frequency of both genotypes in males, there were no significant differences between healthy subjects and patients in terms of age and sex (P > 0.05). Conclusions: Based on the results of this study, it can be concluded that ApoA1 gene polymorphisms were not associated with ALL disease. It was not effective in the formation or exacerbation of it in this population. Also, it could not be identified as a prognostic marker. It should be noted that these findings are the first report of the degree of association of ApoA1 polymorphisms with ALL.

P0349A MISSPROCESSED FORM OF APOLIPOPROTEIN A-I IS SPECIFICALLY ASSOCIATED TO RECURRENT FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Background and Aims Recurrence of idiopathic FSGS, a glomerular disease of unknown aetiology, is a serious complication after kidney transplantation. There are no accurate means to diagnose the relapses or to detect the patients at risk. In an exploratory study we detected Apolipoprotein A-Ib (ApoA-Ib), a high molecular weight form of ApoA-I, specifically in urine of kidney transplanted patients that relapsed of FSGS. The diagnostic performance of ApoA-Ib has been assessed in two independent cohorts obtaining high specificity (94,1 %) and sensitivity (87,5 %) to detect FSGS relapses. It has also a potential to detect patients at risk of relapse as ApoA-Ib predates the recurrence episodes in most of the cases. As urinary ApoA-Ib is strongly associated to primary FSGS we aimed to unravel the nature of the modification present in ApoA-Ib. Method The whole APOA1 gene was sequenced in ApoA-Ib positive and negative patients and the protein structure was studied using 2D electrophoresis followed by mass spectrometry. Results No genetic variations in the APOA1 gene were found in the ApoA-Ib positive patients that could explain the increase in the molecular mass. The mass spectrometry analysis revealed three extra amino acids at the N-Terminal end of ApoA-Ib that were not present in the standard plasmatic form of ApoA-I. These amino acids corresponded to half of the propeptide sequence of the immature form of ApoA-I (proApoA-I). These results suggest that proApoA-I is miss-cleaved producing ApoA-Ib probably due to an altered protease activity in recurrent FSGS patients Conclusion ApoA-Ib, found specifically in urine of recurrent FSGS patients, is a misprocessed form of ApoA-I that retains three aminoacids of the six-aminoacid N-terminal propeptide of proApoA-I. The description of ApoA-Ib could be relevant not only to allow the automated analysis of this biomarker in the clinical laboratory but also to shed light into the molecular mechanism of idiopathic FSGS.