Background/ObjectiveOsteopontin (OPN) and IL-18 are known inflammatory mediators and both participate in a wide range of biological processes linked to immunological disorders. Since an interaction between OPN and IL-18 has not been studied in obesity, we investigated whether: (i) their levels were simultaneously elevated in obese individuals; (ii) OPN was associated with IL-18 in obese individuals and (iii) their levels associated with fasting blood glucose (FBG) and BMI.Subjects and MethodsPBMCs and plasma samples were isolated from 60 individuals including lean as well as overweight and obese individuals. Subcutaneous adipose tissue samples were obtained. OPN and IL-18 were measured by ELISA. OPN and IL-18 mRNA expression was quantified by real time quantitative RT-PCR.ResultsObese individuals exhibited significantly increased circulating OPN levels as compared with lean individuals (obese 2865±101; lean 1681±116 pg/ml; P<0.0001). IL-18 levels were also high in obese individuals (obese 491±39, lean 301±26 pg/ml; P = 0.0009). OPN and IL-18 expression were simultaneously up-regulated (OPN: 5.4-Fold; IL-18: 8.9-Fold; P<0.05) in PBMCs from obese individuals compared to lean group. Adipose tissue from obese individuals had high expression of OPN (7.3-Fold) and IL-18 (9.6-Fold). Plasma OPN levels correlated positively with FBG levels (r = 0.32, P = 0.02). Similarly, IL-18 correlated positively with FBG levels (r = 0.406, P = 0.0042). Stepwise multiple regression analysis showed an independent association of BMI with OPN and IL-18. Interestingly, OPN levels increased progressively with an increase in IL-18 levels (r = 0.52, P = 0.0004). We also examined the regulatory role of IL-18 in OPN secretion from PBMCs. Neutralizing anti-IL-18Rα mAb reduced OPN secretion.ConclusionThese findings represent the first observation that plasma, PBMC and adipose tissue OPN and IL-18 are simultaneously increased and correlate with each other in overweight/obese individuals which may trigger the development of obesity-associated insulin resistance. Moreover, these results provide the direct evidence that IL-18 regulates OPN production in PBMCs.

Oat bran is suggested to attenuate atherosclerotic conditions by regulating dyslipidemia, endothelial function, and oxidative damage. Through the measurement of oxidized polyunsaturated fatty acid (PUFA), oxidative stress, and inflammation status in liver and heart tissues of apolipoprotein E −/− (ApoE −/− ), mice fed with high fat diet (HFD) or HFD with oat bran (HFD + Oat) were investigated. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), PUFA and over 40 types of its oxidized products were assessed. The HFD + Oat group had augmented adrenic acid (ADA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and suppressed n-3 docosapentaenoic acid levels in the liver tissues compared to the HFD group. Arachidonic acid (ARA) and α-linolenic acid (ALA) levels were elevated and ADA was suppressed in the heart tissues of the HFD + Oat group compared to the HFD group. Furthermore, enzymatically mediated oxidized ARA product levels (9-, 11-and 20-HETE [hydroxyeicosatetraenoic acid], and PGF 2α ) were augmented and those of the oxidized DHA products (4-, 7-, 10-, 11-, 13-, and 14-HDHA [hydroxy-docosahexaenoic acid]) were reduced in the liver tissues of the HFD + Oat group. It also increased 17-F 2t -dihomo-isoprostane and 7-F 2t -dihomo-isofuran derived from nonenzymatic oxidation of ADA in the heart and liver tissues, and those from ALA namely 16-F 1t -phytoprostane and 16(RS)-13-epi-STΔ 14 -9-phytofuran. Our study showed oat bran to be a weak antioxidant and lacked anti-inflammatory properties in atherosclerotic mice. Elevation of oxidized PUFA products that are potentially proinflammatory and vasoconstrictors (HETE, PGF 2α ) with simultaneous reduction of those that are anti-inflammatory (HDHA) may not be desirable in the pathogenesis of atherosclerosis.

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