Weight Loss and Short-Chain Fatty Acids Reduce Systemic Inflammation in Monocytes and Adipose Tissue Macrophages from Obese Subjects

Abstract

Background: Chronic low-grade systemic inflammation is a characteristic of obesity that leads to various non-communicable diseases. Weight loss and SCFAs are potential strategies for attenuating obese systemic inflammation. Methods: Blood samples were collected from 43 obese subjects (BMI ≥ 30 kg/m2) scheduled for laparoscopic bariatric sleeve surgery, 26 obese subjects at follow-up 12–18 months post-surgery and 8 healthy weight subjects (BMI 18.5–24.9 kg/m2). Monocytes were isolated from blood and adipose tissue macrophages from visceral adipose tissue of obese subjects only. Isolated cells stimulated with 1 ng/mL LPS and treated simultaneously with 300 mM of sodium acetate or 30 mM of sodium propionate or butyrate and supernatant were harvested after 15 h incubation. TNF-α and IL-6 cytokines were measured via ELISA and mRNA gene expression of FFAR2 and FFAR3, HDAC1, HDAC2 and HDAC9, RELA and NFKB1 and MAPK1 via RT-qPCR. Results: TNF-α and IL-6 production and NFKB1 and RELA mRNA expression were significantly decreased in follow-up subjects compared to baseline. SCFAs significantly reduced TNF-α and IL-6 and altered FFAR and HDAC mRNA expression in monocytes and macrophages from obese subjects. Conclusion: Weight loss and ex vivo SCFA treatments were successful in combatting systemic inflammation in obesity. Results highlighted molecular changes that occur with weight loss and as a result of SCFA treatment.

Keywords

• obesity
• systemic inflammation
• weight loss
• short-chain fatty acids
• FFAR
• HDAC