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Obesity is a risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Adipose tissue (AT) extracellular vesicles (EVs) could play a role in obesity and T2DM associated CVD progression via the influence of their specific cargo on gene expression in recipient cells. The aim of this work was to evaluate the effects of AT EVs of patients with obesity with/without T2DM on reverse cholesterol transport (RCT)-related gene expression in human monocyte-derived macrophages (MDMs) from healthy donors. AT EVs were obtained after ex vivo cultivation of visceral and subcutaneous AT (VAT and SAT, respectively). ABCA1 , ABCG1 , PPARG , LXRβ (NR1H2) , and LXRα (NR1H3) mRNA levels in MDMs as well as in origine AT were determined by a real-time PCR. T2DM VAT and SAT EVs induced ABCG1 gene expression whereas LXRα and PPARG mRNA levels were simultaneously downregulated. PPARG mRNA levels also decreased in the presence of VAT EVs of obese patients without T2DM. In contrast ABCA1 and LXRβ mRNA levels tended to increase with the addition of obese AT EVs. Thus, AT EVs can influence RCT gene expression in MDMs during obesity, and the effects are dependent on T2DM status.

The nuclear factors PPARγ, RORα, and LXRβ 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 LXRβ (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, LXRβ 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 study aimed to investigate tissue-specific gene expression of ABCA1 and ABCG1, encoding cholesterol transporters, as well as PPARG, LXRβ (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 β = 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 (β = -0.602, p = 0.003 and β = -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 β = -0.819, p = 0.004 and β = -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.