ena-STUDY-UNIVERSITY OF ABERDEEN-13-05-2018-22:23:26:328-2033
Diet-induced obesity is independent of metabolic endotoxemia, Tlr4 signalling and hypothalamic inflammation.
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.
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.