Effect of folate deficiency and leptin on inflammatory response

• Main Authors: Pei-Hsuan Chan, 詹培萱
• Other Authors: Bi-Fong Lin
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/99772663398897769584

碩士 === 國立臺灣大學 === 生化科技學系 === 104 === Leptin plays a big role in metabolism and energy expenditure. Folate is an essential nutrient that involved in synthesis of nucleotide and protein. The present study is to investigate the role of folate deficiency and leptin in inflammatory response. There are three parts of the experiments: In experiment I, to investigate the effect of folate deficiency on inflammatory response of mice under LPS- or LPS/leptin-injection, male C57BL/6J mice were divided into NF-f0 (0 mg/kg folate), and NF-f1 (2 mg/kg folate). LPS and LPS/leptin were intraperitoneally injected into mice at 26- and 27-week-old. The results showed that serum leptin level in LPS/leptin-injected mice, serum IL-1β level in LPS- and LPS/leptin-injected mice were significantly higher in the NF-f0 group. After feeding for 31 weeks, 37-week-old mice were sacrificed. Serum leptin and pro-inflammatory cytokines level, inflammatory mediators in liver and adipose tissue, ratio of macrophage, CD4+ T cells, Th1, Th2, Treg in spleen, and ratio of macrophage in PEC, were analyzed. Splenocytes were stimulated with ConA or ConA/leptin, while PECs were stimulated with LPS or LPS/leptin. The results showed that folate deficiency enhanced serum IL-1β, MCP-1 and IFN-γ level, tended to enhance serum leptin, TNF-α and IL-6. Folate deficiency decreased Foxp3 mRNA expression in the adipose tissue, enhanced MCP-1, IL-1β mRNA in the liver and M1 macrophage ratio in PEC, decreased M2 macrophage ratio in PEC. Folate deficiency enhanced TNF-α, IL-6, IFN-γ secretion in splenocytes and TNF-α, IL-6, MCP-1 secretion in PEC. Furthermore, leptin addition induced IFN-γ secretion in splenocytes and TNF-α secretion in PEC. In experiment II, to investigate the effect of folate deficiency on inflammatory response, mice were divided into NF-f0 and NF-f1. After feeding for 18 weeks, 25-week-old mice were sacrificed. The results showed that folate deficiency enhanced serum leptin and pro-inflammatory cytokines level, decreased F4/80 mRNA in the liver and CD4+T cell population in splenocytes, also enhanced secretion of TNF-α, IL-6, IFN-γ in splenocytes and TNF-α, IL-6, MCP-1, IL-1β in PEC. Besides, leptin addition enhanced secretion of IL-6 and IFN-γ under LPS or ConA stimulation in splenocytes. In experiment III, to investigate the effect of folate deficiency on inflammatory response of mice fed high-fat diet, mice were divided into HF-f0 (0 mg/kg folate) and HF-f1 (2 mg/kg folate). After feeding for 20 weeks, 26-week-old mice were sacrificed. The results showed that folate deficiency enhanced serum leptin and pro-inflammatory cytokines level, enhanced leptin and TNF-α mRNA in the adipose tissue, decreased IL-1β, Foxp3 and MRC1 mRNA in the adipose tissue as well as IL-1β and MRC1 mRNA expression in the liver. Besides, leptin addition enhanced TNF-α and IL-6 secretion in both splenocytes and PEC under LPS stimulation. In conclusion, folate deficiency enhanced serum leptin and pro-inflammatory cytokines level. Both folate deficiency and leptin may exacerbate inflammatory response.