Effects of high-fat diet and folate status on immune regulation
Date Issued
2015
Date
2015
Author(s)
Hsiu, Yu-Lin
Abstract
It is controversial that obesity increase the mortality of acute inflammation. In this study, we prolonged feeding time of high-fat diet and lowered the dose of LPS to investigate whether obesity reduced the lifespan of mice in acute inflammation. C57BL/6J male mice were fed high-fat diet for 22 weeks, serum cytokines and blood T cell subtype were examined, and mice were intraperitoneally injected with a 10 mg/kg body weight (BW) LPS to induce acute inflammation, and lifespan was observed. Results indicated that obese mice had higher serum IL-6 and lower CD4+ T cells proportion, however obese mice had longer lifespan in acute inflammation, and lower hapatic IL-1β mRNA expression. Correlation between hepatic inflammatory cytokines expression and lifespan was not observed, indicating that obesity may not reduce the lifespan in acute inflammation. Furthermore, we used LPS-induced acute inflammation murine model to study if folate deficiency could shorten the lifespan. C57BL/6J male mice fed folate-deficient diet for 12 weeks were injected with 15 mg/kg BW LPS, lifespan and body temperature were observed. Results showed that folate deficiency didn’t influence the lifespan of C57BL/6J mice in acute inflammation, but there was a positive correlation between lifespan and body temperature at 11 hr after LPS-induced inflammation. Our study also investigated whether folate status may affect fat deposit and immune cells activation in high-fat diet feeding. C57BL/6J male mice were fed high-fat diet containing different content of folate: HF-f0/a (0 mg, 1% antibiotics added), HF-f0 (0 mg), HF-f1 (2 mg) and HF-f10 (20 mg) per kg diet. Mice fed for 20 weeks were sacrificed at 26 weeks of age. Blood triglyceride, total cholesterol, HDL-C, LDL-C, antibody level, and hepatic lipid concentration were analyzed. Immune cells activation was examined by spleen T lymphocyte proliferation, spleen naïve T cells population, and cytokines produced by splenocytes and primary macrophages. Hepatic inflammatory-related cytokines mRNA expression was examined by qPCR. Results showed that HF-f0 had higher adipose tissue weight and higher F4/80+ macrophage infiltration but lower serum total cholesterol, HDL-C and LDL-C concentration, serum triglyceride wasn’t observed significant differences among groups. On the contrary, HF-f0 had higher hepatic cholesterol content. In addition, spleen T lymphocyte proliferation was significantly decreased, but the percentage of spleen naïve T cells was increased in the HF-f0 group. IL-2 was increased when cells were activated, while IL-6 was decreased in splenocytes of the HF-f0 group. Primary macrophages in peritoneal fluid in the HF-f0 group also had higher IL-6 secretion, and hepatic IL-6 and IL-1β mRNA expressions were elevated, but total IgA and IgG in the serum were reduced. HF-f10 significantly increased serum IgA. On the other hand, antibiotics could not affect mice growth but increased serum cholesterol, reduced hepatic cholesterol, reduced IL-2 and IL-6 secretion of splenocytes, increased IL-10 secretion of splenocytes in LPS stimulation, also reduced hepatic IL-6 and IL-1β mRNA expressions, and elevated serum IgA production compared to the HF-f0 group. To summarize, high-fat diet and folate deficiency could not affect the lifespan of mice in LPS-induced inflammation but may block cholesterol transport and cause lipid accumulate in liver, inhibit T cell differentiation/activation, and may promote inflammatory response because of higher IL-6 production of primary macrophages and elevated hepatic IL-6 and IL-1β mRNA expressions. Folate deficiency may also depress humoral immunity by reduced IgA and IgG level. In contrast, folate supplementation could benefit immune regulation and induce antibodies production.
Subjects
high-fat diet
acute inflammation
folate
immune response
SDGs
Type
thesis
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