Naslov (srp)

Imunometabolički fenotip miševa sa dominantnim tip 1 i tip 2 imunskim odgovorom u eksperimentalnom modelu gojaznosti

Autor

Jovičić, Nemanja U., 1981-

Doprinosi

Pejnović, Nada.
Lukić, Miodrag, 1941-
Lalić, Nebojša, 1958-
Arsenijević, Nebojša, 1958-
Tanasković, Irena.

Opis (eng)

Obesity is chronic condition which represents major risk factor for developing various metabolic disorders including insulin resistence, type 2 diabetes, NAFLD, and aterosclerosis. Studies have shown that Immune reactivity plays an important role in obesity-associated metabolic disorders. Complex immune mechanisms and cytokines orchestrate inflammatory response and metabolic disturbances in this context. It has been shown in humans and rodents that suceptibility to various diseases depends on immunogenetic factors. These factors also determines dominant type of immune response. Obesity is characterized by visceral adipose tissue inflammation and systemic low grade chronic inflammation (metaflammation). Mechanisms of metaflammation are 177 not completely understood. Anti-inflammatory М2/Th2 type of response dominates in lean adipose tissue, while pro-inflammatory М1/Th1 prevails in obese adipose tissue. The IL-33/ST2 axis has a protective role in adiposity and atherosclerosis, but its role in obesity-associated metabolic disorders requires further clarification. Interleukin-33 (IL-33), binds to its plasma membrane receptor, heterodimeric complex consisted of membrane-bound ST2L and IL-1R accessory protein. Recent studies suggest that IL-33 plays an important role in liver diseases. Increased expression of IL-33 and its receptor ST2 are in positive correlation with degree of liver fibrosis. The objective of this study was to compare development of obesity, adipose tissue and liver immunophenotype, glucoregulation, liver steatosis, inflammation and fibrosis in C57Bl/6 and BALB/c mice fed chow and high fat diet. As C57Bl/6 mice preferentially develop Th1 immune response and BALB/c mice Th2-type cytokine polarization, they are regarded as prototypic Th1 and Th2-type mouse strains, respectively. To investigate the role of IL-33/ST2 signaling in obesity-associated metabolic disorders, we used ST2-deficient (ST2) and wild type (WT) BALB/c mice maintained on a high-fat diet (HFD) for 24 weeks. We demonstrated significant differences in immunometabolic phenotype between two mouse strains. In response to HFD C57Bl/6 mice exhibited higher weight gain, higher adiposity, increased glycemia, increased amount of visceral adipose tissue and more pronounced liver inflammation and fibrosis. These effects were associated with increased number of Th1 immune cells in visceral adipose tissue and proinflammatory cytokines in livers and sera. We show dissociation of liver steatosis and fibrosis related to Th1 and Th2 dominance in mice.

Opis (srp)

Gojaznost je hronično oboljenje koje predstavlja glavni faktor rizika za razvoj metaboličkih poremećaja uključujući insulinsku rezistenciju, tip 2 dijabetes, nealkoholnu masnu bolest jetre, aterosklerozu i druge bolesti. Istraživanja su jasno pokazala da imunski sistem ima značajnu ulogu u metaboličkim poremećajima. Ovo otkriće uključuje i značaj inflamacije posredovane ćelijama urođene i stečene imunosti u razvoju 172 gojaznosti i metaboličkog sindroma. U humanoj populaciji i eksperimentalnim životinjama jasno je pokazano da osetljivost na veliki broj bolesti može zavisiti od imunogenetskih faktora koji pored ostalog određuju i preovlađujući tip imunskog odgovora. Gojaznost karakteriše postojanje inflamacije u uvećanom visceralnom adipoznom tkivu i hronična sistemska inflamacija niskog stepena, označena kao metabolička inflamacija (metaflamacija), čiji molekulski mehanizmi nastanka i delovanja nisu dovoljno razjašnjeni. U fiziološkim uslovima, u masnom tkivu preovlađuje antiinflamatorni M2/Th2 tip imunskog odgovora, dok u gojaznom masnom tkivu preovlađuje proinflamatorni M1/Th1 imunski odgovor. Uloga IL-33/ST2 signalnog puta u metaboličkim poremećajima izazvanim gojaznošću nije dovoljno ispitana. Nakon oslobađanja iz ćelije, IL-33 ostvaruje svoje funkcije vezujući se za specifični receptor koji je po strukturi heterodimer koji čine ST2 molekul i IL-1R aksesorni protein (IL-1RacP). Sve više studija ukazuje na značajnu ulogu IL-33 u različitim oboljenjima jetre. Utvrđeno je da su povećana ekspresija IL-33 i njegovog receptora ST2 u pozitivnoj korelaciji sa razvojem fibroze jetre kod ljudi ali i u različitim animalnim modelima bolesti. Glavni cilj studije je bio ispitivanje razlika u razvoju gojaznosti, inflamacije u visceralnom masnom tkivu, glikoregulacije, steatoze, steatohepatitisa i fibroze jetre u eksperimentalnom modelu gojaznosti primenom dijete sa visokim sadržajem masti (engl. high-fat diet, HFD) u C57BL/6 miševa sa dominantnim Th1 i BALB/c miševa sa dominantnim Th2 imunskim odgovorom. Takođe je ispitivana i uloga IL-33/ST2 signalnog puta u metaboličkim poremećajima izazvanim gojaznošću u eksperimentalnom modelu gojaznosti primenom HFD u ST2 deficijentnih BALB/c miševa u odnosu na Th1 i Th2 dominantne miševe.

Jezik

srpski

Datum

2016

Licenca

Creative Commons licenca
Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 2.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 2.0 Austria License.

CC BY-NC-ND 2.0 AT

http://creativecommons.org/licenses/by-nc-nd/2.0/at/

Identifikatori