BioProject

The gut microbiota has been proposed to contribute to obesity via the leakage of bacterial lipopolysaccharide (LPS) activating Toll-like receptor-4 (TLR4) and resulting in low-grade inflammation. More...

The gut microbiota has been proposed to contribute to obesity via the leakage of bacterial lipopolysaccharide (LPS) activating Toll-like receptor-4 (TLR4) and resulting in low-grade inflammation. Knockout of Tlr4 or its coreceptor Cd14 reportedly attenuates diet-induced obesity in mice.We compared adiposity, gut microbiota composition, and hypothalamic inflammation in Tlr4-/-, Cd14-/-, and Wild-Type mice fed high-fat (HFD) or low-fat diet (LFD) after 8-weeks. Futher Wild -Type mice were fed HFD or LFD for 16-weeks.Body weight, adiposity, and energy intake were unchanged in Tlr4-/- or Cd14-/- mice fed HFD compared to Wild-Type mice. Wild-Type caecal microbiota composition differed from Tlr4-/- and Cd14-/- mice, with only relatively small differences between diets. RNAseq showed increased hypothalamic expression of Serpina3n and Socs3 in Wild-Type mice at 16-weeks, with few other genes altered. Real-time PCR showed increased hypothalamic Socs3 expression at 8-weeks in Wild-Type mice but no increase in genes associated with inflammation in Wild-Type or Tlr4-/- mice. In situ hybridisation showed increased hypothalamic Serpina3n and Socs3 expression at 8-weeks and 16-weeks.Loss of Tlr4 or Cd14 does not protect mice from diet-induced obesity and that Serpina3n, a marker of neuroprotection, rather than genes associated with inflammation, is the main hypothalamic response to HFD. Less...