Uticaj delecije gena Mif na razvoj gojaznosti i steatoze jetre kod miševa na režimu ishrane obogaćene fruktozom

Abstract

Hronična inflamacija niskog intenziteta ima važnu ulogu u patogenezi metaboličkih poremećaja, kao što su gojaznost i dislipidemija, koji su često izazvani ishranom obogaćenom fruktozom i predstavljaju faktore rizika za razvoj steatoze jetre i dijabetesa tipa 2. Faktor migracije makrofaga (MIF) je plejotropni citokin koji pored uloge u regulaciji imunskog odgovora može da reguliše metaboličke procese i oslobađanje insulina iz pankreasa, međutim njegova uloga u metaboličkoj inflamaciji nije još uvek dovoljno razjašnjena. Dodatno, pokazano je da se miševi sa deletiranim genom Mif odlikuju izmenjenom osetljivošću na insulin i glukozu. Stoga, fokus ovog rada je bio usmeren ka boljem razumevanju molekularnih mehanizama metaboličkih efekata MIF-a, kao i ka rasvetljavanju kontroverzne uloge ovog citokina u razvoju poremećaja lipidnog metabolizma u jetri i visceralnom masnom tkivu miševa na režimu ishrane obogaćene fruktozom.

Chronic low-grade inflammation plays an important role in the development of metabolic disorders such as obesity and dyslipidemia, which are often induced by a fructose-enriched diet and are risk factors for the development of hepatic steatosis and type 2 diabetes. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that, in addition to its role in regulating the immune response, can regulate metabolic processes and the release of insulin from the pancreas; however its role in metabolic inflammation is not well understood. In addition, mice with a deleted Mif gene were found to have altered sensitivity to insulin and glucose. Therefore, the focus of this work was to better understand the molecular mechanisms of the metabolic effects of MIF and to elucidate the controversial role of this cytokine in the development ofdyslipidemia in the liver and visceral adipose tissue of mice on fructose-enriched diet.