The effect of Sodium Butyrate supplementation on serum level of Lipopolysaccharide binding protein and expression levels of NFκB, TLR4, TNFα genes in obese individuals on a weight-loss diet: A Triple- Blind, Randomized, Placebo- Controlled Clinical Trial

Abstract

Abstract - 1 - ABSTRACT Background: Due to the high prevalence of obesity and its inflammatory disorders, it seems necessary to find anti-inflammatory therapeutic approaches to improve the status of these patients. According to the previous animal, cell line, and human studies, Sodium Butyrate (NaB) has been effective in reducing inflammation and inflammatory factors. Given that no human studies have investigated the effects of NaB on the expression levels of genes involved in the inflammatory pathway (NFκB, TLR4, and TNFα), the aim of this study was to investigate the effects of NaB supplementation along with calorie restriction on serum lipopolysaccharide binding protein (LBP) and expression level of Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), Toll-like receptor 4 (TLR4), and tumor necrosis factor alpha (TNFα) genes in obese adult patients. Methods: This triple-blind randomized controlled clinical trial was conducted among 50 obese adults. Eligible persons were randomly divided into NaB or placebo groups (n=25 in each group). The NaB group received a 600 mg NaB capsule daily and the placebo group received the same amount of placebo (starch) for 8 weeks. All subjects received a low-calorie diet according to their BMI and physical activity. The amount of energy required for each person was calculated based on a weight loss of 0.5 to 1 kg per week (500 kcal less than daily requirement) and was calculated by the Mifflin formula for men and women. LBP serum level was evaluated using ELISA kit. mRNA expression levels of NFκB, TLR4, and TNFα genes were evaluated using real-time PCR technique. In this study, three models were used to adjust the effect of basic values and confounding factors. In the first model, baseline values were contorolled. In the second model, changes in waist circumference (WC), energy intake, and physical activity were additionally adjusted for. In the final model, effect of changes in Homeostatic Model Assessment of insulin resistance (HOMA-IR) in addition to Model 2 was contorolled. Abstract 2 Results: Intra-group changes in serum LBP level in the NaB group was significantly decreased after the end of the intervention (P<0.001), but this reduction was not significant in the placebo group. Serum LBP was also significantly decreased, compared to the placebo group (P=0.04) after 8 weeks. In addition, the expression of mRNA of NFκB (P=0.02) and TNFα (P=0.04) genes after controlling possible confounders decreased significantly in the intervention group, compared to the placebo group. In contrast, TLR4 expression level in the NaB group showed a non-significant decrease, compared to that in the placebo group (P=0.06). Conclusion: The present study provided evidence that NaB supplementation can cause significant reductions in inflammatory factors. Studies with larger sample size and longer duration of intervention are recommended to confirm the results. KEYWORDS: Sodium Butyrate; Obesity; Inflammation; Lipopolysaccharide-binding protein ; Lipopolysaccharide; Nuclear factor kappa-light chain-enhancer of activated B cells ; Toll-like receptor 4; Tumor necrosis factor