Melatonin Attenuates Dextran Sodium Sulfate Induced Colitis in Obese Mice

Abstract

Epidemiological studies have indicated that obesity is an independent risk factor for colitis and that a high-fat diet (HFD) increases the deterioration of colitis-related indicators in mice. Melatonin has multiple anti-inflammatory effects, including inhibiting tumor growth and regulating immune defense. However, the mechanism of its activity in ameliorating obesity-promoted colitis is still unclear. This study explored the possibility that melatonin has beneficial functions in HFD-induced dextran sodium sulfate (DSS)-induced colitis in mice. Here, we revealed that HFD-promoted obesity accelerated DSS-induced colitis, while melatonin intervention improved colitis. Melatonin significantly alleviated inflammation by increasing anti-inflammatory cytokine release and reducing the levels of proinflammatory cytokines in HFD- and DSS-treated mice. Furthermore, melatonin expressed antioxidant activities and reversed intestinal barrier integrity, resulting in improved colitis in DSS-treated obese mice. We also found that melatonin could reduce the ability of inflammatory cells to utilize fatty acids and decrease the growth-promoting effect of lipids by inhibiting autophagy. Taken together, our study indicates that the inhibitory effect of melatonin on autophagy weakens the lipid-mediated prosurvival advantage, which suggests that melatonin-targeted autophagy may provide an opportunity to prevent colitis in obese individuals.

Long-Term Overconsumption of Fat and Sugar Causes a Partially Reversible Pre-inflammatory Bowel Disease State

“…It would have been intersting to determine cytokine profile in HF-fed mice compared to HFHS-mice it is one of the limitations of our study. However, it can be assumed from other studies that HF diet increased pro-inflammatory cytokines secretion ( 36 ). Considering that such impaired immune defenses are a hallmark of IBD, this strengthens the link between sugar homeostasis and intestinal inflammation ( 37 ).…”

Research progress on the relationship between Paneth cells-susceptibility genes, intestinal microecology and inflammatory bowel disease

“…There are many bacteria or foreign bacteria in the lumen. PCs can directly detect bacteria and express large quantities of particulate matter containing antibacterial factors through TLRs, which induces degranulation to increase the concentration of antibacterial factors in the intestinal cavity, inhibit the invasion of exogenous microorganisms, and control the microbial population in the small intestine[ 68 ]. This is an important reason why the microbial colonization density in the small intestine is lower than that in the large intestine.…”

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“…It would have been intersting to determine cytokine profile in HFfed mice compared to HFHS-mice it is one of the limitations of our study. However, it can be assumed from other studies that HF diet increased pro-inflammatory cytokines secretion (36). Considering that such impaired immune defenses are a hallmark of IBD, this strengthens the link between sugar homeostasis and intestinal inflammation (37).…”