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COMPARISON OF CITOKINE AND ADIPOKINE PROFILES IN DAT-KO(DAT-/-), WISTAR AND ZUCKER (FA+/FA+) RATS FED BY A RATION WITH HIGH FAT AND FRUCTOSE CONTAINMENT


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Abstract

Obesity is associated with a sluggish inflammation. Since the close relationship between immunity and metabolic disturbances reflects the interaction of leptin (Lep) and ghrelin (Ghr), and involvement of Lep in dopaminergic system, the aim of this study were to compare the cytokine profile in DAT-KO rats with a knockout of the dopamine transporter gene (DAT), in Zucker (ZF) rats with mutation fa in the Lep receptor gene Lepr and the outbred rats of Wistar (W) line in obesity. Two groups of male rats of each line received a diet according to AIN93M, or a diet with an excess of fats and fructose (HFCR). On the 30th day, W rats were bled from the tail vein. On the 65th day, the weights of body, organs and adipose tissue of the animals were determined, and the blood plasma was collected. Cells from spleen and adipose tissue were cultured for 72 hours 1·106 cells/ml for cytokine production in vitro. Cytokine and adipokine levels were determined on a Luminex 200 analyzer using Bio-Plex kits. Cytokine levels, Lep content and L/Ghr ratio were lowered in DAT-KO rats. In ZF MCP-1, GRO/RC, Lep and L/Ghr ratio were significantly elevated, which was accompanied by lower concentrations of IL-10 and IL-5 in comparison to W. HFCR produced significant increase of Lep and L/Ghr ratio in DAT-KO and ZF and promoted rise in MCP-1 and IL-10 in ZF. Only transitory elevation of MCP-1, IL-17, IL-10 and IL-5 was noticed in W. Spleen and fatty tissue cells W and ZF have different ability for production of IFN-α, IL-10 and IL-17A. HFCR had a suppressor effect on the production of cytokines in vitro. Reliable correlations were found between the mass of fat, the L/Ghr ratio, the spleen mass and the levels of MCP-1, GRO / KC (positive) and IL-5, IL-17A (negative). Hereby the interrelation was demonstrate of the dopaminergic system and the signaling pathway of leptin/leptin receptor in the regulation of metabolism, and the biomarker significance was confirmed of the L/Ghr ratio in the formation of metabolic and immunoregulatory disorders in obesity.


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