[Factors governing development of nonalcoholic fatty liver disease and insulin resistance in obesity]

Biomed Khim. 2018 Sep;64(5):444-450. doi: 10.18097/PBMC20186405444.
[Article in Russian]

Abstract

The factors promoting development of non-alcoholic fatty liver disease in patients with obesity and different state of carbohydrate metabolism have been studied. 43 patients were examined; these included 26 patients with abdominal obesity (BMI=52.9±7.9 kg/m2). The control group consisted of 17 conditionally healthy donors without obesity (BMI=18.9-24.9 kg/m2), seven of them 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. The concentration of IL-6 and TNF-a was measured in blood serum by the ELISA method. In patients with obesity with diabetes mellitus type 2 (DM2), a significant increase in the serum level of proinflammatory 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, an increase in the area of fatty inclusions (relative to the group without type 2 diabetes) was recorded. The study of the HSP70 gene expression in peripheral blood mononuclear cells allowed its significant increase relative to the comparison group. The relationship between the level of expression of the HSP70 gene in metabolically active tissues (visceral, subcutaneous adipose tissue and liver) established in all obese patients with the serum content of proinflammatory cytokines (IL-6 and TNF-a) may indicate suppression of HSP70 expression in these tissues, background of systemic and local inflammation in obesity.

Issledovany faktory, sposobstvuiushchie razvitiiu nealkogol'noĭ zhirovoĭ bolezni pecheni u bol'nykh ozhireniem s razlichnym sostoianiem uglevodnogo obmena. Obsledovano 43 patsienta, iz nikh 26 patsientov s abdominal'nym ozhireniem (IMT=52,9±7,9 kg/m2). Kontrol'nuiu gruppu sostavili 17 uslovno zdorovykh donora, ne imeiushchikh ozhireniia (IMT – 18,9-24,9 kg/m2), iz nikh 7 chelovek – gruppa sravneniia, kotoraia byla vkliuchena v issledovanie dlia sopostavleniia rezul'tatov po opredeleniiu urovneĭ tkanespetsificheskoĭ ékspressii mRNK gena HSP70, (kodiruiushchego belok teplovogo shoka 70). Issledovanie otnositel'nogo urovnia ékspressii genov provodili metodom PTsR v rezhime real'nogo vremeni. Kontsentratsiiu IL-6 i TNF-a izmeriali v syvorotke krovi s pomoshch'iu tverdofaznogo immunofermentnogo “séndvich” metoda (ELISA). U bol'nykh ozhireniem s sakharnym diabetom 2 (SD 2) tipa vyiavleno dostovernoe uvelichenie syvorotochnogo urovnia provospalitel'nykh tsitokinov po sravneniiu s gruppoĭ bez SD 2 tipa i kontrolem. Rezul'taty gistologicheskogo issledovaniia bioptatov pecheni u patsientov s ozhireniem pozvolili konstatirovat' naibolee vyrazhennye izmeneniia v gruppe bol'nykh SD 2 tipa. Nezavisimo ot stadii nealkogol'noĭ zhirovoĭ distrofii pecheni u bol'nykh ozhireniem s SD 2 tipa registrirovalos' uvelichenie ploshchadi zhirovykh vkliucheniĭ (otnositel'no gruppy bez SD 2 tipa). Issledovanie ékspressii gena HSP70 v mononuklearakh perifericheskoĭ krovi pozvolilo vyiavit' ego znachitel'noe povyshenie otnositel'no gruppy sravneniia. Ustanovlennye nami u vsekh bol'nykh ozhireniem vzaimosviazi urovnia ékspressii gena HSP70 v metabolicheski aktivnykh tkaniakh (vistseral'naia, podkozhnaia zhirovaia tkan' i pechen') s syvorotochnym soderzhaniem provospalitel'nykh tsitokinov (IL-6 i TNF-a), mogut ukazyvat' na podavlenie ékspressii HSP70 v étikh tkaniakh, na fone sistemnogo i lokal'nogo vospaleniia pri ozhirenii.

Keywords: expression of HSP70; fat tissue; insulin resistance; liver biopsy; non-alcoholic fatty liver disease; obesity.

MeSH terms

  • Diabetes Mellitus, Type 2
  • Humans
  • Insulin Resistance*
  • Leukocytes, Mononuclear
  • Liver
  • Non-alcoholic Fatty Liver Disease*
  • Obesity*