Decreased expression of the PPARG, ADIPOQ, and SLC2A4 genes in subcutaneous adipose tissue in bariatric patients with morbid obesity and type 2 diabetes mellitus

BACKGROUND: Adipose tissue (AT) is an active endocrine organ that produces biologically active molecules — adipokines, which participate in lipid and glucose metabolism. The imbalance of adipokine secretion in obesity is a consequence of AT dysfunction, which at the molecular genetic level is manifested as changes in the expression of the key genes, and can be complicated by the development of metabolic disorders, in particular type 2 diabetes mellitus (T2DM).

AIM: The aim of this study was to investigate the expression level of PPARG, ADIPOQ, LEP, SLC2A4 genes in subcutaneous and visceral adipose tissue (SAT and VAT) in bariatric patients with obesity and T2DM, as well as to assess the correlation of adiponectin and leptin serum concentrations with the expression of corresponding genes.

MATERIALS AND METHODS: The single-center, cross-sectional, two-sample, comparative, observational case-control study included patients with grade II, III, IV obesity with/without T2DM, as well as non-obese individuals who applied to the Pavlov First Saint Petersburg State Medical University for bariatric (patients) and planned abdominal surgeries (control group), SAT and VAT samples, as well as blood serum, were collected. Real-time polymerase chain reaction was used to determine the mRNA levels of target genes in AT. Adiponectin and leptin serum concentrations were assesed by enzyme immunoassay.

RESULTS: The group of bariatric patients included 53 patients (mean age 44.1±11.2 years; body mass index (BMI) over 35 kg/m²), including 26 patients with a diagnosis of T2DM and 27 without T2DM. The control group included 15 individuals without obesity, metabolic disorders and T2DM (mean age 46.7±12.8; BMI less than 30 kg/m²). In patients with obesity and T2DM, a decrease in the level of PPARG, ADIPOQ and SLC2A4 gene expression in SAT was observed compared to the control group. The level of PPARG and ADIPOQ gene expression was also reduced in VAT in patients with obesity and T2DM compared to the control group. The observed changes in gene expression in obesity were associated with a decrease in adiponectin and an increase in leptin serum concentrations, with the most pronounced decrease in adiponectin concentration in patients with obesity and T2DM. Unidirectional positive correlations were observed in the expression levels of PPARG, ADIPOQ, LEP, SLC2A4 genes in SAT and VAT in the total cohort.

CONCLUSION: The development of T2DM on the basis of obesity and BMI of more than 35 kg/m² is associated with reduced expression levels of the PPARG, ADIPOQ and SLC2A4 genes in SAT, a marked decrease in the concentration of adiponectin and an increase in the concentration of leptin in the blood serum.

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