[AdipoRon Effect on Expression of Lipid Metabolism Genes in Cultured Human Primary Macrophages].

Atherosclerosis is characterized by excessive uptake of cholesterol-rich low-density lipoprotein (LDL) by vascular wall macrophages. The macrophages are transformed into foam cells, lipids accumulate in the intima of arteries, atherosclerotic plaques arise, and cardiovascular diseases develop. Adiponectin is an adipose tissue adipokine and possess anti-atherogenic and anti-inflammatory activities, which are mediated by adiponectin binding to its receptors AdipoR1 and AdipoR2. To exert its anti-atherogenic effect, adiponectin may regulate the reverse cholesterol transport and prevent foam cells formation. The small-molecule adiponectin receptor agonist AdipoRon was assumed to modulate expression of reverse cholesterol transport and inflammation genes in human macrophages. Several AdipoRon concentrations (0, 5, 10, and 20 µM) were tested for effect on expression of the lipid metabolism genes ABCA1, ABCG1, APOA1, NR1H3 (LXRα), NR1H2 (LXRß), PPARG, and ACAT1 and the inflammation genes IL6, TNFA, and TLR4 in cultured human primary macrophages and the THP-1 macrophage cell line. Cell viability was measured using the MTS assay. ABCA1, ABCG1, APOA1, NR1H3, NR1H2, PPARG, ACAT1, IL6, TNFA, and TLR4 mRNA levels in human primary macrophages were assessed by real-time PCR. The PPARG and ABCA1 relative mRNA levels were found to increase in human primary macrophages treated with 5 or 10 µM AdipoRon for 24 h. A higher AdipoRon concentration (20 µM) was cytotoxic to macrophages, especially THP-1 cells. The effect of AdipoRon on human macrophages and potential adiponectin receptor agonists are of interest to study in view of the need to develop new approaches to atherosclerosis prevention and treatment.

Expression of Genes Encoding Nuclear Factors PPARγ, LXRß, and RORα in Epicardial and Subcutaneous Adipose Tissues in Patients with Coronary Heart Disease.

The nuclear factors PPARγ, RORα, and LXRß are involved in transcriptional control of adipogenesis and implicated in glucose and lipid metabolism. In adipose tissues, they regulate inflammation. This study focuses on expression of the PPARG, RORA, and LXRß (NR1H2) genes in epicardial and subcutaneous adipose tissues in patients with coronary heart disease as well as with concomitant abdominal obesity. In patients with coronary heart disease and abdominal obesity, PPARG mRNA level in subcutaneous adipose tissue was reduced in comparison with control group. In patients with total coronary occlusions, LXRß mRNA level in epicardial adipose tissue was reduced, and it positively correlated with plasma HDL cholesterol. Thus, in cases of concomitant abdominal obesity and chronic total coronary occlusions, coronary heart disease is characterized by down-regulated expression of the genes of various transcriptional adipogenesis-regulating factors in adipose tissue.

[The Expression of Genes Encoding ABCA1 and ABCG1 Transporters and PPARγ, LXRß, and RORα Transcriptional Factors in Subcutaneous and Visceral Adipose Tissue in Women with Metabolic Syndrome].

The study aimed to investigate tissue-specific gene expression of ABCA1 and ABCG1, encoding cholesterol transporters, as well as PPARG, LXRß (NR1H2), and RORA, encoding the most important transcriptional regulators of lipid metabolism, in subcutaneous and visceral adipose tissue (SAT and VAT) in women with metabolic syndrome. It was shown that the ABCG1 mRNA SAT/VAT ratio decreases with age and correlates with the development of metabolic syndrome. After age adjustment, women have reduced chances of metabolic syndrome development when ABCG1 gene expression in SAT is higher relative to VAT than women with VAT ABCG1 gene expression higher or comparable to SAT: OR = 0.15 (95% CI 0.03-0.76), p = 0.023. The ABCA1 mRNA SAT/VAT ratio positively correlated with HDL cholesterol levels (after age adjustment ß = 0.350, p = 0.046), therefore individuals with higher ABCA1 mRNA level in SAT relative to VAT had elevated HDL levels. The ABCA1 mRNA level in SAT was decreased in smokers (p = 0.001). There was a negative correlation between the PPARG mRNA level in SAT with body mass index and waist circumference in the general sample (ß = -0.602, p = 0.003 and ß = -0.642, p = 0.001, respectively, after age adjustment). A decrease of the PPARG mRNA SAT/VAT ratio was associated with elevated plasma insulin level and the insulin resistance index HOMA-IR ß = -0.819, p = 0.004 and ß = -1.053, p = 0.008, respectively, after age adjustment). Thus, the study has shown that the ratio of ABCA1, ABCG1, and PPARG genes expression in different types of adipose tissue (SAT/VAT) could be a significant factor that predicts the development of atherogenic dyslipidemia, metabolic syndrome, and insulin resistance in obesity.

[Epicardial and subcutenious adipose tissue adiponectin gene expression in coronary artery disease patients].

Aim To determine the expression of adiponectin gene (ADIPOQ) and the content of high-molecular-weight adiponectin (HMWA) in epicardial (EAT) and subcutaneous adipose tissue (SCAT) in patients with ischemic heart disease (IHD).Material and methods Paired samples of EAT and SCAT and blood serum were withdrawn from patients with IHD after bypass surgery and 16 subjects without IHD (comparison group). Matrix RNA (mRNA) level was measured using real-time polymerase chain reaction. HMWA levels in EAT and SCAT were evaluated by Western blotting. Serum adiponectin concentration was measured immunoenzymatically. For all patients, echocardiography was performed to measure the EAT thickness; coronarography was performed to determine severity of coronary atherosclerosis.Results Serum adiponectin concentration was lower in IHD patients than in the comparison group (p<0.001). Levels of ADIPOO gene mRNA and HMWA in SCAT were lower in IHD patients than in the comparison group (р=0.020 and p=0.003, respectively). The HMWA level in EAT was lower with the EAT thickness of 8 mm compared to the HMWA level in IHD patients with EAT ≤8 mm (p=0.034).Conclusion The decreased serum concentration of antiatherogenic adiponectin and the reduced expression of ADIPOQ gene in SCAT (mRNA, HMWA) are associated with IHD.