Sustained Inflammation Induced by LPS Leads to Tolerable Anorexia and Fat Loss via Tlr4 in Mice

Abstract

Background Sustained inflammation is implicated in a variety of pathological conditions like infection, obesity and type 2 diabetes. Lipid metabolism is crucial to support immune response during infection of bacteria. However, how sustained inflammation affects lipid metabolism, especially in white adipose tissue remains largely unknown. Methods Sustained inflammation was induced by daily injection of Lipopolysaccharide (LPS). Tlr4 knockout mice were used to study the mechanism. Inflammation and lipid metabolism were evaluated by quantitative PCR, white blood cell counting, nuclear magnetic resonance, fat cell size quantification, lipolysis and fatty acid uptake assays, respiratory exchange ratio, and energy expenditure. Results Here, we found that sustained inflammation leads to fat loss in mice with a quick loss and gradual increase manner. Moreover, LPS injection leads to inflammation, anorexia, decreased lipid anabolism, and increased lipid catabolism. Mechanically, we show that LPS induces fat loss, inflammation, anorexia, and alteration of lipid metabolism mainly dependent on Tlr4 . Interestingly, sustained inflammation induces less fat loss, especially in epididymal white adipose tissue, than pair-feeding, and pair-feeding has no significant effect on inflammation and leads to less fatty acid uptake, more lipid catabolism and energy expenditure than LPS injection. In addition, we demonstrate that short-term sustained inflammation leads to relative long-term tolerance for LPS-induced anorexia, inflammation and altered lipid metabolism. Conclusion These findings demonstrate that sustained inflammation induced by LPS leads to tolerable anorexia and fat loss via Tlr4 in mice, and provide new insights into the effect of sustained inflammation on lipid metabolism and subsequent tolerance.

Untitled

“…As reported earlier, this study's significantly decreasing body and gut weight indicates LPS-induced systemic toxicity. [33,34] FOS supplementation reduces systemic toxicity to maintain body weight. This finding suggests that FOS in an appropriate amount can protect the gut from LPS damage, repair tissue cells, and keep the gut healthy.…”