High fat diet‐induced obesity leads to proinflammatory response associated with higher expression of NOD2 protein

Abstract

Obesity has been reported to be associated with low grade inflammatory status. We studied the inflammatory response of immune cells and signaling molecules associated with inflammatory responses in diet‐induced obesity. C57BL mice were fed diets containing 5% fat (Control) or 20% fat and 1% cholesterol (HFD) for 24 wks. Splenocytes (1 × 107 cells) were stimulated with 10 μg/mL of LPS for 6 or 24 hrs. Production of IL‐1β, IL‐6 and TNF‐α and expression levels of NOD2, STAT3, pSTAT3 were determined. Consumption of HFD resulted in significantly more weight gain (28.2±0.6g in HFD vs. 15.4±0.8g in control). After stimulation with LPS for 6 hrs, production of IL‐1β and TNF‐α were significantly higher in HFD group. After 24 hrs of LPS stimulation, splenocytes from HFD group produced significantly higher levels of IL‐6 (10.02 ± 0.66 ng/mL in HFD vs. 7.33 ± 0.56 ng/mL in control) and IL‐1β(121.34 ± 12.72 pg/mL in HFD vs. 49.78 ± 6.58 pg/mL in control). There were no significant differences in STAT3 and pSTAT3 expression levels between HFD and control groups. However, expression level of NOD2 proteins determined by western blot analysis was significantly higher in HFD group (60% higher in HFD group compared with control, p<0.05). NOD2 contributes to the induction of inflammation by activation of NF‐κB. These findings suggest that diet‐induced obesity is associated with increased inflammatory response of immune cells and higher expression of NOD2 may contribute to these changes.Supported by Korea Research Foundation Grant funded by the Korean Government(KRF‐331‐2008‐1‐C00305) and the Basic Science Research Program funded by the Ministry of Education, Science and Technology (2009‐0063409).