The role of immune mechanisms in development of metabolic syndrome in obesity

doctoral thesis

• Title (croatian): Uloga imunosnih mehanizama u razvoju metaboličkoga sindroma u debljini
• Author: Sonja Marinović
• Mentor: Bojan Polić (mentor)
• Mentor: Danka Grčević (komentor)
• Committee member: Ana Galov (predsjednik povjerenstva)
• Granter: University of Zagreb; Faculty of Science; Zagreb
• Defense date and country: 2018-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 57 - Biological sciences. Physical anthropology. Biodiversity

Abstract

More than billion of obese and overweight people live currently in the world. A significant number of them develop diabetes mellitus type 2 (DM2) and non-alcoholic fatty liver disease (NAFLD). Mechanisms that induce inflammation and trigger transition from pre-diabetes to DM2 or from hepatic steatosis to non-alcoholic steatohepatitis (NASH) are still unclear. In this research I found that γδ T cells are enriched in visceral adipose tissue and they produce proinflammatory cytokines. In response to high fat diet (HFD), there is increase in number of γδ T cells that produce IL-17A. Research on NAFLD revealed that initiating event, in response to high calorie diet, is the increase in expression of the NKG2D ligand H60 on hepatocytes. Upregulation of ligands leads to mobilisation of γδ T cells through an NKG2D engagement that induces an increase in IL-17A. Lack of either γδ T cells, NKG2D or IL-17A significantly decreases development of liver fibrosis.

Abstract (croatian)

Trenutno na svijetu živi više od milijarde pretilih ljudi i onih s prekomjernom težinom. Značajan broj njih obolijeva od šećerne bolesti tipa 2 (DM2) i nealkoholne bolesti masne jetre (NAFLD). Mehanizmi koji induciraju upalu u debljini i uzrokuju prijelaz iz stadija pre-dijabetesa u DM2 ili iz stadija jetrene steatoze u nealkoholni steatohepatitis (NASH) su još uvijek nejasni. U ovom istraživanju otkrila sam da se γδ limfociti T nalaze u velikom broju u visceralnom masnom tkivu i da mogu sintetizirati proupalne citokine. Kao odgovor na visoko-kalorijsku prehranu bogatu mastima dolazi do povećanja broja γδ limfocita T koji proizvode IL-17A. Istraživanja na NAFLD-u pokazala su da kao odgovor na visokokalorijsku dijetu, dolazi do povećanog izražaja NKG2D liganda H60 na hepatocitima. Povećani izražaj NKG2D liganda dovodi do mobilizacije γδ stanica kroz aktivaciju receptora NKG2D koji potiče sintezu IL-17A. Nedostatak γδ limfocita T, receptora NKG2D ili citokina IL-17A značajno smanjuje razvoj fibroze jetre.

• Keywords: diabetes mellitus type 2; γδ T cells; IL-17A; non-alcoholic fatty liver disease; NKG2D receptor; stress induced molecules.
• Keywords (croatian): diabetes mellitus tip 2; γδ limfociti T; IL-17A; nealkoholna masna bolest jetre; receptor NKG2D; stresom inducirane molekule.
• Language: croatian
• URN:NBN: urn:nbn:hr:217:223572
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2020-09-04
• Created on: 2018-09-04 11:59:24