In this manuscript by Gobron et al the authors provide evidence that the effects of k cells in the intestine on bone are complex producing both factors that stimulate bone formation and others that modulate GIP action on bone. The data is interesting and the experiments appear to be carefully performed. Several questions: (1) GLP-1 release from L cells may also be regulated by GIP, neuromodulation in rodents. GLP-1 and 2 can also modulate bone turnover. The authors show that GLP-1 levels do not change after xenin injection (Fig 3I). Did they measure the GLP-1, GLP-2 levels in their genetic mouse models in particular GIP-DT? (2) the authors are not seeing an effect on osteoblast activity, bone formation rate on histomorphometry but do see effects on gene expression (alkaline phosphatase and collagen) and markers of bone turnover (P1NP) why the discrepancy? (3) not intuitively clear why the k cells would make both xenin and GIP. The idea of sequential effects is interesting. A schematic diagram would be helpful to put their findings within a physiological context.

All my concerns have been adequately addressed.