Factors Governing Development of Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Obesity

Abstract

The factors promoting development of non-alcoholic fatty liver disease in patients with obesity and different state of carbohydrate metabolism have been investigated in 43 patients. These included 26 patients with abdominal obesity (BMI = 52.9 ± 7.9 kg/m2) and 17 conditionally healthy donors (control group) without obesity (BMI = 18.9–24.9 kg/m2). Seven (of 17) conditionally healthy persons formed a comparison group that was included to compare the results of study on the levels of tissue-specific expression of HSP70 mRNA. The study of mRNA expression was performed by real-time PCR. Blood serum concentrations of IL-6 and TNF-α were evaluated by the ELISA method. In obese patients with diabetes mellitus type 2 (DM2), a significant increase in the serum level of pro-inflammatory cytokines was found in comparison with the group of patients without DM2 and control. The results of histological examination of liver biopsy specimens in obese patients revealed the most pronounced changes in the group of DM2 patients. Regardless of the stage of nonalcoholic fatty liver disease in obese DM2 patients, there was an increase in the area of fatty inclusions (relative to the group without DM2). The study of the HSP70 gene expression in peripheral blood mononuclear cells revealed a significant increase versus the comparison group. The relationship between the level of the HSP70 gene expression in metabolically active tissues (visceral, subcutaneous adipose tissue and liver) and the serum content of proinflammatory cytokines (IL-6 and TNF-α) found in all obese patients may indicate suppression of HSP70 expression in these tissues under conditions of systemic and local inflammation in obesity.