Transgenic <i>Fgfr3</i>^<i>ach/+</i> mice preferentially develop visceral obesity that is prevented upon sFGFR3 treatment.

<p>(<b>A</b>), body weight of vehicle-treated WT and <i>Fgfr3</i>^<i>ach/+</i> mice and sFGFR3 treated <i>Fgfr3</i>^<i>ach/+</i> mice after 10 weeks of ND or HFD challenge. (<b>B</b>), abdominal lean:fat ratio. (<b>C</b>) epididymal adipose tissue (eAT) weight and (<b>D</b>) subcutaneous adipose tissue (scAT) weight per g of body weight. (<b>E</b>) scAT and (<b>F</b>) eAT adipocyte area (μm²). (<b>G</b>) scAT and (<b>H</b>) eAT scattering of adipocytes according to their diameter. Data are represented as mean ± SD (n = 8–10 mice to each group). Data followed normal distribution. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 versus vehicle-treated WT, ^#<i>p</i><0.05, ^##<i>p</i><0.01 versus vehicle-treated <i>Fgfr3</i>^<i>ach/+</i>; Student’s <i>t</i> test.</p

Glucose metabolism is altered in transgenic <i>Fgfr3</i>^<i>ach/+</i> mice and restored with sFGFR3 treatment.

<p>Fasting glycemia and insulinemia of mice following 10 weeks of (<b>A</b>) ND or (<b>B</b>) HFD. (<b>C</b>) glucose tolerance test; glucose levels were normalized to the value of time -15 min and area under the curve corresponding to each group of mice. (<b>D</b>) Mice pancreas insulin content (immunohistochemistry of paraffin-embedded sections, red: insulin; green: glucose; blue: DAPI staining), mean of pancreas islets normalized to total surface and mean of islets number in each group under HFD condition. (<b>E</b>) Liver H&E and PAS staining under HFD condition. (<b>F</b>) H&E staining of hepatic nodules. Data are represented as mean ± SD (n = 8–10 mice to each group). Data followed normal distribution. **<i>p</i><0.01, ***<i>p</i><0.001 versus vehicle-treated WT, ^#<i>p</i><0.05, ^##<i>p</i><0.01 versus vehicle-treated <i>Fgfr3</i>^<i>ach/+</i>; Student’s <i>t</i> test.</p

MSCs isolated from untreated or sFGFR3-treated <i>Fgfr3</i>^<i>ach/+</i> mice show pre-engagement towards adipogenesis with no alteration of the insulin response compared to WT mice.

<p><b>(A)</b> Expression of genes involved in different steps of adipogenesis differentiation (Genes are listed in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195876#pone.0195876.s005" target="_blank">S2 Table</a></b>). Expression was normalized to HPRT, RPL6 and RPL13a expression and expressed as percent of change compared to WT. (<b>B</b>) Cells were stimulated with 50nM of insulin for 0, 5, 15 or 30 min or with 0, 1, 10, 50 or 100nM of insulin during 5 min. P-Erk1/2 expression, normalized to Erk1/2 total expression, was expressed as normalized value to WT. Data are represented as mean ± SD. Data followed normal distribution. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 versus vehicle-treated WT, ^#<i>p</i><0.05, ^##<i>p</i><0.01 versus vehicle-treated <i>Fgfr3</i>^<i>ach/+</i>; Two-way ANOVA with Tukey’s multiple test.</p

Untreated <i>Fgfr3</i>^<i>ach/+</i> mice displayed an elevated inflammatory baseline prevented by sFGFR3 treatment.

<p>Untreated <i>Fgfr3</i>^<i>ach/+</i> mice displayed an elevated inflammatory baseline prevented by sFGFR3 treatment.</p

Children with achondroplasia preferentially develop abdominal obesity without an increase in blood glucose levels.

<p>(<b>A</b>), Weight, height and BMI measurements and corresponding height-to-age and BMI-to-age z-scores in the three age groups ranging (n = 73 data points in the [0–3] years old group, n = 61 data points in the [4–8] years old group and n = 36 data points in the [9–18] years old group). (<b>B</b>), Schematic representation of the different regions of interest (ROI) evaluated by DXA. (<b>C</b>), Android:gynoid fat ratio measurement in the three age groups ranging (n = 4 data points in the [0–3] years old group, n = 6 data points in the [4–8] years old group and n = 9 data points in the [9–18] years old group). (<b>D</b>), Plasmatic fasting glucose concentration in the two age groups ranging [4–8] and [9–18] years old (n = 16 data points in the [4–8] years old group and n = 12 data points in the [9–18] years old group). Horizontal lines represent normal values. Data are represented as mean ± SD, **<i>p</i><0.01, ***<i>p</i><0.001. Results of post hoc analyses: ^a significantly different between [0–3] and [4–8] groups; ^b significantly different between [0–3] and [9–18] groups; ^c significantly different between [4–8] and [9–18] groups.</p