Response to “Is the Reg3α (HIP/PAP) Protein Really an Obesogenic Factor?”

We are grateful to Gonzalez et al. (2015) for their comments and remarks, which give us the opportunity to clarify a few points that were probably not sufficiently detailed in the manuscript (Secq et al., 2014). In our work we demonstrate that TgPAP/HIP mice, which express the PAP/HIP transgene in their liver and have a high level of circulating PAP/HIP, are obese. This statement is based on the augmented body weight but not only: circulating leptin, which is known to correlate with the amount of adipose tissue, is significantly elevated in these mice as presented in Figure 2. Also, we report in the results section that at the end of the experiments, animal were sacrificed and liver, kidney, testes, lungs, heart, stomach, and pancreas were dissected and weighted. No significant difference in weight was found between TgPAP/HIP and control mice. However, macroscopic inspection showed that intra-peritoneal, retroperitoneal, and peri-cardiac fat accumulationwasmore abundant in TgPAP/HIP than in control mice, indicating that increased body weight was due to fat accumulation. Showing quantitative data was not considered essential (and was not required during the reviewing process). Gonzalez et al. also refer to an apparent discrepancy between data presented in Figure 1A and D. Animals included in experiments described in Figure 1A are actually different from those used in experiment described in Figure 1D, contrary to what Gonzalez et al. assumed. In addition, the goal of the latter experiment being to evaluate a possible correlation between circulating levels of PAP/HIP and body weight, we included both male and female mice. Female mice are smaller compared to male. This is why the average body weights are smaller in Figure 1D than in Figure 1A. In conclusion, our data support the hypothesis that PAP/HIP protein is an obesogenic factor. It remains, however, possible that induction of obesity depends not only on circulating PAP/HIP concentration but also on the environment in which animal are housed, because PAP/HIP is a major modulator of the intestinal flora and the composition of intestinal flora is known to influence the metabolism, including obesity development.