No public access
master's thesis
The Expression dynamics of molecules important of the immune system in visceral adipose tissue cells in obesity

Anamaria Đukić (2016)
Sveučilište u Rijeci
Odjel za biotehnologiju
Metadata
TitleDinamika ekspresije molekula važnih za aktivaciju imunološkog sustava u stanicama visceralnog masnog tkiva u debljini
AuthorAnamaria Đukić
Mentor(s)Bojan Polić (thesis advisor)
Abstract
Šećerna bolest tipa 2 (engl. Type 2 Diabetes Mellitus, T2D) je kronična metabolička bolest koja se razvija kao kombinacija rezistencije perifernih tkiva na hormon inzulin i neučinkovitog odgovora β-stanica Langerhansovih otočića gušterače. Očituje se kao stanje kronične hiperglikemije s poremećenim metabolizmom ugljikohidrata, bjelančevina i masti. Pretilost je jedan od ključnih rizičnih čimbenika za razvoj inzulinske rezistencije (engl. Insulin Resistance, IR) i T2D. Masno tkivo je građeno od adipocita i stromalno-vaskularne frakcije stanica koja sadrži i stanice imunosnog sustava. Komponente imunosnog sustava značajno su promijenjene u pretilosti i T2D. To se prvenstveno odnosi na promijenjene razine proupalnih citokina i kemokina te promjene u brojnosti i aktivacijskom statusu različitih populacija leukocita koji pripadaju Th1 tipu imunosnog odgovora, što ukazuje na razvoj upale. Smatra se da visceralno masno tkivo (engl. Visceral Adipose Tissue, VAT) predstavlja glavni izvor kronične sistemske upale niskog intenziteta koja dovodi do razvoja IR u pretilosti. U posljednje vrijeme intenzivno se istražuju učinci specifičnih citokina i proupalne aktivacije imunosnih stanica u VAT-u, budući da gubitak protuupalnih (homeostatskih) mehanizama imunosnih stanica dovodi do upale tkiva koja pridonosi razvoju IR. Cilj ovog diplomskog rada bio je praćenje izražaja gena u ranoj fazi upale VAT-a. U eksperimentalnom radu koristila sam mišji model prehranom inducirane pretilosti (engl. Diet Induced Obesity, DIO). Od posebnog su interesa za istraživanje bili geni koji kodiraju proupalne citokine i citokine koji sudjeluju u staničnom stresu te potiču upalu masnog tkiva. Rezultati pokazuju da se razina genskog izražaja IFN-β, citokina uključenog u stanični stres, povećava već u prvim danima uslijed početka DIO, a ta razlika postaje izraženija nakon 4 tjedana. Očekivano, kod miševima podvrgnutih DIO ustanovljeni je povećani izražaj proupalnih citokina IL-1β i IL-17a. Također, ustanovljeno je i da u ranim fazama DIO ne dolazi do povećanja u izražaju IL-7, citokina koji ima važnu ulogu u preživljenju i proliferaciji limfocita te ga izražavaju CD45- stromalno-vaskularne stanice VAT-a. Rezultati mojih istraživanja pokazuju da već u prvim danima inicijacije DIO, dolazi do povećanog izražaja gena za proupalne citokine i citokine koji sudjeluju u staničnom stresu, što stvara preduvjete za razvoj upale VAT-a i pokretanje kaskade događaja koji potencijalno mogu dovesti do nastanka IR i razvoja T2D.
Keywordstype 2 diabetes obesity visceral adipose tissue chronic inflammation proinflammatory cytokines
Parallel title (English)The Expression dynamics of molecules important of the immune system in visceral adipose tissue cells in obesity
Committee MembersAstrid Krmpotić (committee chairperson)
Igor Jurak (committee member)
Bojan Polić (committee member)
GranterSveučilište u Rijeci
Lower level organizational unitsOdjel za biotehnologiju
PlaceRijeka
StateCroatia
Scientific field, discipline, subdisciplineBIOTECHNICAL SCIENCES
Biotechnology
Study programme typeuniversity
Study levelgraduate
Study programmeBiotechnology in medicine
Academic title abbreviationmag. biotech. in med.
Genremaster's thesis
Language Croatian
Defense date2016-07-22
Parallel abstract (English)
Type 2 diabetes mellitus (T2D) is a chronic metabolic disease which develops as a combination of peripheral tissues resistance to the hormone insulin and ineffective response of pancreatic islets β-cells. It manifests as a state of chronic hyperglycemia with altered metabolism of carbohydrates, proteins and fats. Obesity is one of the key risk factors for the development of insulin resistance (IR) and T2D. Adipose tissue is populated with adipocytes and stormal-vascular fraction which contains immune cells. The components of the immune system are significantly altered in obesity and T2D. Changes in levels of pro-inflammatory cytokines and chemokines and changes in number and activation state of different populations of leukocytes belonging to the Th1 immune response, indicates the development of inflammation. It is considered that visceral adipose tissue (VAT) represents a predominant source of chronic systemic inflammation that leads to the development of IR in obesity. Recently, intensive investigations include the effects of specific cytokines and pro-inflammatory activation of immune cells in VAT because loss of anti-inflammatory (homeostatic) mechanisms of immune cells leads to inflammation of tissue which contributes to the development of the IR. The aim of this master thesis was to analyze gene expression in the early phase of VAT inflammation. In the experimental work I used an animal model of diet-induced obesity (DIO). Genes encoding pro-inflammatory cytokines and cytokines involved in the cellular stress were of the particular interest for this study. Results shown that the level of gene expression of IFN-β, a cytokine involved in cellular stress, was increased in the first few days following DIO. The difference in the increased gene expression becomes more detectable after 4 weeks of DIO. Besides, the mice underwent DIO established increased expression of pro-inflammatory cytokines IL-1β and IL-17a. It is also found that in the early stages of DIO, the expression of IL-7 wasn't elevated. IL-7 is a cytokine that plays an important role in the survival and proliferation of lymphocytes and it is expressed by the CD45- stromal-vascular cells in VAT. The results in master thesis show that in first days after the iniciation of DIO, there is an increased gene expression of pro-inflammatory cytokines and cytokines involved in cellular stress. That potentially creates environment for the development of VAT inflammation and the initiation of the cascade that can potentially lead to IR and the development of T2D.
Parallel keywords (Croatian)šećena bolest tipa 2 pretilost visceralno masno tkivo kronična upala proupalni citokini
Resource typetext
Access conditionNo public access
URN:NBNhttps://urn.nsk.hr/urn:nbn:hr:193:047510
CommitterLea Lazzarich