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.
Highlights
IntroductionSystematic inflammation is largely driven by adipose tissue macrophages (ATMs)
Chronic low-grade systemic inflammation is a hallmark feature of obesity
This study presents an analysis of systemic inflammation in obesity, the molecular pathways driving inflammation, and explores two strategies for attenuating inflammation in obesity, including bariatric surgery and short-chain fatty acids (SCFAs) treatment
Summary
Systematic inflammation is largely driven by adipose tissue macrophages (ATMs). M1 macrophages exacerbate systemic inflammation by production of pro-inflammatory cytokines such as TNF-α and IL-6 [3]. Obese systemic inflammation can be driven by metabolic endotoxemia, a state typified by elevated levels of circulating endotoxins including lipopolysaccharides (LPS). Metabolic endotoxemia occurs as a result of gut dysbiosis, altering tight junction proteins in the intestinal lumen, increasing intestinal permeability, permitting LPS to infiltrate circulation [4]. Elevated levels of metabolic and bacterial danger signals such as free fatty acids (FFAs) and LPS initiate systemic inflammation by binding to Toll-like receptors (TLRs) and activating NF-κB and MAPK pro-inflammatory pathways leading to transcription of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β [5,6]
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