Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia
Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a maj...
Gespeichert in:
| Veröffentlicht in: | PloS one 2018-04, Vol.13 (4), p.e0195876-e0195876 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0195876 |
|---|---|
| container_issue | 4 |
| container_start_page | e0195876 |
| container_title | PloS one |
| container_volume | 13 |
| creator | Saint-Laurent, Celine Garcia, Stephanie Sarrazy, Vincent Dumas, Karine Authier, Florence Sore, Sophie Tran, Albert Gual, Philippe Gennero, Isabelle Salles, Jean-Pierre Gouze, Elvire |
| description | Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients, and is associated to life-threatening complications including increasing risk of cardiovascular pathologies. We have thus decided to study obesity in patients and to use the mouse model to evaluate if soluble FGFR3 therapy, an innovative treatment approach for achondroplasia, could also impact the development of this significant complication.
To achieve this, we have first fully characterized the metabolic deregulations in these patients by conducting a longitudinal retrospective study, in children with achondroplasia Anthropometric, densitometric measures as well as several blood parameters were recorded and compared between three age groups ranging from [0-3], [4-8] and [9-18] years old. Our results show unexpected results with the development of an atypical obesity with preferential fat deposition in the abdomen that is remarkably not associated with classical complications of obesity such as diabetes or hypercholosterolemia. Because it is not associated with diabetes, the atypical obesity has not been studied in the past even though it is recognized as a real problem in these patients. These results were validated in a murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was observed. Unexpected alterations in glucose metabolism were highlighted during high-fat diet. Glucose, insulin or lipid levels remained low, without the development of diabetes. Very interestingly, in achondroplasia mice treated with soluble FGFR3 during the growth period (from D3 to D22), the development of these metabolic deregulations was prevented in adult animals (between 4 and 14 weeks of age). The lean-over-fat tissues ratio was restored and glucose metabolism showed normal levels. Treating Fgfr3ach/+ mice with soluble FGFR3 during the growth period, prevented the development of these metabolic deregulations in adult animals and restored lean-over-fat tissues ratio as well as glucose metabolism in adult animals.
This study demonstrate that achondroplasia patients develop an atypical obesity with preferential abdominal obesity not associated with classical complications. These results suggest that achondroplasia induces a |
| doi_str_mv | 10.1371/journal.pone.0195876 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2024796197</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A534577803</galeid><doaj_id>oai_doaj_org_article_35dc66f3290840868b6ce19b5ac9a2cd</doaj_id><sourcerecordid>A534577803</sourcerecordid><originalsourceid>FETCH-LOGICAL-c792t-2115d444c9da047388d15a84431e268414db4d5f6e2d6bc01927c1d4e7dac9443</originalsourceid><addsrcrecordid>eNqNk11r2zAUhs3YWLtu_2BshsFYL5Lp2_bNIJSmDRQK3cetkCU5VlAsV1LC8u8nN25JSi-GL2zOec57fF7pZNlHCKYQF_D7ym18J-y0d52eAljRsmCvslNYYTRhCODXB98n2bsQVgBQXDL2NjtBFaOoAvA0U5fC213euxA7EYXNg7Ob2up8fjW_w3lstRd9ynu91V0MQyAXcdcbmViVgtb165TJXZO7WgcTd7npciFb1ynveiuCEe-zN42wQX8Y32fZ7_nlr4vryc3t1eJidjORRYXiBEFIFSFEVkoAUuCyVJCKkhAMNWIlgUTVRNGGaaRYLdPMqJBQEV0oIauEnWWf97q9dYGPBgWOACJFxWBVJGKxJ5QTK957sxZ-x50w_CHg_JILH420mmOqJGMNTj6VBJSsrJnUsKpp6iWQVEnrx9htU6-1kskFL-yR6HGmMy1fui2nZZXOCiWB871A-6zsenbDhxggpGIFoFuY2G9jM-_uNzpEvjZBamtFp93mYUaKEUR0QL88Q192YqSWIg1rusalf5SDKJ9RTGhRlAAnavoClR6l10amm9eYFD8qOD8qSEzUf-NSbELgi593_8_e_jlmvx6wrRY2tsNVjcZ14Rgke1B6F4LXzZOzEPBhcR7d4MPi8HFxUtmnw8N8KnrcFPwPO-4SEQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2024796197</pqid></control><display><type>article</type><title>Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Saint-Laurent, Celine ; Garcia, Stephanie ; Sarrazy, Vincent ; Dumas, Karine ; Authier, Florence ; Sore, Sophie ; Tran, Albert ; Gual, Philippe ; Gennero, Isabelle ; Salles, Jean-Pierre ; Gouze, Elvire</creator><contributor>Bader, Michael</contributor><creatorcontrib>Saint-Laurent, Celine ; Garcia, Stephanie ; Sarrazy, Vincent ; Dumas, Karine ; Authier, Florence ; Sore, Sophie ; Tran, Albert ; Gual, Philippe ; Gennero, Isabelle ; Salles, Jean-Pierre ; Gouze, Elvire ; Bader, Michael</creatorcontrib><description>Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients, and is associated to life-threatening complications including increasing risk of cardiovascular pathologies. We have thus decided to study obesity in patients and to use the mouse model to evaluate if soluble FGFR3 therapy, an innovative treatment approach for achondroplasia, could also impact the development of this significant complication.
To achieve this, we have first fully characterized the metabolic deregulations in these patients by conducting a longitudinal retrospective study, in children with achondroplasia Anthropometric, densitometric measures as well as several blood parameters were recorded and compared between three age groups ranging from [0-3], [4-8] and [9-18] years old. Our results show unexpected results with the development of an atypical obesity with preferential fat deposition in the abdomen that is remarkably not associated with classical complications of obesity such as diabetes or hypercholosterolemia. Because it is not associated with diabetes, the atypical obesity has not been studied in the past even though it is recognized as a real problem in these patients. These results were validated in a murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was observed. Unexpected alterations in glucose metabolism were highlighted during high-fat diet. Glucose, insulin or lipid levels remained low, without the development of diabetes. Very interestingly, in achondroplasia mice treated with soluble FGFR3 during the growth period (from D3 to D22), the development of these metabolic deregulations was prevented in adult animals (between 4 and 14 weeks of age). The lean-over-fat tissues ratio was restored and glucose metabolism showed normal levels. Treating Fgfr3ach/+ mice with soluble FGFR3 during the growth period, prevented the development of these metabolic deregulations in adult animals and restored lean-over-fat tissues ratio as well as glucose metabolism in adult animals.
This study demonstrate that achondroplasia patients develop an atypical obesity with preferential abdominal obesity not associated with classical complications. These results suggest that achondroplasia induces an uncommon metabolism of energy, directly linked to the FGFR3 mutation. These data strongly suggest that this common complication of achondroplasia should be included in the clinical management of patients. In this context, sFGFR3 proved to be a promising treatment for achondroplasia by normalizing the biology at different levels, not only restoring bone growth but also preventing the atypical visceral obesity and some metabolic deregulations.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0195876</identifier><identifier>PMID: 29652901</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Achondroplasia ; Achondroplasia - complications ; Achondroplasia - diagnosis ; Achondroplasia - drug therapy ; Achondroplasia - genetics ; Adipose tissue ; Adolescent ; Age ; Animal models ; Animal tissues ; Animals ; Anthropometry ; Biology and Life Sciences ; Biomarkers ; Blood Glucose ; Bone growth ; Cardiovascular diseases ; Care and treatment ; Child ; Child, Preschool ; Children ; Complications ; Complications and side effects ; Densitometers ; Deregulation ; Diabetes ; Diabetes mellitus ; Disease ; Disease Models, Animal ; Dwarfism ; Endocrinology and metabolism ; Energy metabolism ; Female ; Fibroblast growth factor receptors ; Fibroblasts ; Genetic aspects ; Glucose ; Glucose metabolism ; Growth factors ; Health aspects ; Health risks ; High fat diet ; Human health and pathology ; Humans ; Infant ; Infant, Newborn ; Insulin ; Insulin - metabolism ; Life Sciences ; Lipid Metabolism ; Male ; Medical innovations ; Medicine and Health Sciences ; Mesenchymal Stem Cells ; Mesenchymal Stromal Cells - metabolism ; Metabolism ; Mice ; Mice, Transgenic ; Mutation ; Normalizing ; Obesity ; Obesity - etiology ; Obesity - prevention & control ; Patients ; Pediatrics ; People and Places ; Phosphatase ; Receptor, Fibroblast Growth Factor, Type 3 ; Receptor, Fibroblast Growth Factor, Type 3 - pharmacology ; Receptor, Fibroblast Growth Factor, Type 3 - therapeutic use ; Risk factors ; Rodents ; Sabatier, Paul (1854-1941) ; Santé publique et épidémiologie ; Secondary Prevention ; Stem cells ; Therapy</subject><ispartof>PloS one, 2018-04, Vol.13 (4), p.e0195876-e0195876</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Saint-Laurent et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2018 Saint-Laurent et al 2018 Saint-Laurent et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c792t-2115d444c9da047388d15a84431e268414db4d5f6e2d6bc01927c1d4e7dac9443</citedby><cites>FETCH-LOGICAL-c792t-2115d444c9da047388d15a84431e268414db4d5f6e2d6bc01927c1d4e7dac9443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898762/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898762/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29652901$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04496705$$DView record in HAL$$Hfree_for_read</backlink></links><search><contributor>Bader, Michael</contributor><creatorcontrib>Saint-Laurent, Celine</creatorcontrib><creatorcontrib>Garcia, Stephanie</creatorcontrib><creatorcontrib>Sarrazy, Vincent</creatorcontrib><creatorcontrib>Dumas, Karine</creatorcontrib><creatorcontrib>Authier, Florence</creatorcontrib><creatorcontrib>Sore, Sophie</creatorcontrib><creatorcontrib>Tran, Albert</creatorcontrib><creatorcontrib>Gual, Philippe</creatorcontrib><creatorcontrib>Gennero, Isabelle</creatorcontrib><creatorcontrib>Salles, Jean-Pierre</creatorcontrib><creatorcontrib>Gouze, Elvire</creatorcontrib><title>Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients, and is associated to life-threatening complications including increasing risk of cardiovascular pathologies. We have thus decided to study obesity in patients and to use the mouse model to evaluate if soluble FGFR3 therapy, an innovative treatment approach for achondroplasia, could also impact the development of this significant complication.
To achieve this, we have first fully characterized the metabolic deregulations in these patients by conducting a longitudinal retrospective study, in children with achondroplasia Anthropometric, densitometric measures as well as several blood parameters were recorded and compared between three age groups ranging from [0-3], [4-8] and [9-18] years old. Our results show unexpected results with the development of an atypical obesity with preferential fat deposition in the abdomen that is remarkably not associated with classical complications of obesity such as diabetes or hypercholosterolemia. Because it is not associated with diabetes, the atypical obesity has not been studied in the past even though it is recognized as a real problem in these patients. These results were validated in a murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was observed. Unexpected alterations in glucose metabolism were highlighted during high-fat diet. Glucose, insulin or lipid levels remained low, without the development of diabetes. Very interestingly, in achondroplasia mice treated with soluble FGFR3 during the growth period (from D3 to D22), the development of these metabolic deregulations was prevented in adult animals (between 4 and 14 weeks of age). The lean-over-fat tissues ratio was restored and glucose metabolism showed normal levels. Treating Fgfr3ach/+ mice with soluble FGFR3 during the growth period, prevented the development of these metabolic deregulations in adult animals and restored lean-over-fat tissues ratio as well as glucose metabolism in adult animals.
This study demonstrate that achondroplasia patients develop an atypical obesity with preferential abdominal obesity not associated with classical complications. These results suggest that achondroplasia induces an uncommon metabolism of energy, directly linked to the FGFR3 mutation. These data strongly suggest that this common complication of achondroplasia should be included in the clinical management of patients. In this context, sFGFR3 proved to be a promising treatment for achondroplasia by normalizing the biology at different levels, not only restoring bone growth but also preventing the atypical visceral obesity and some metabolic deregulations.</description><subject>Achondroplasia</subject><subject>Achondroplasia - complications</subject><subject>Achondroplasia - diagnosis</subject><subject>Achondroplasia - drug therapy</subject><subject>Achondroplasia - genetics</subject><subject>Adipose tissue</subject><subject>Adolescent</subject><subject>Age</subject><subject>Animal models</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Anthropometry</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Blood Glucose</subject><subject>Bone growth</subject><subject>Cardiovascular diseases</subject><subject>Care and treatment</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Complications</subject><subject>Complications and side effects</subject><subject>Densitometers</subject><subject>Deregulation</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Disease</subject><subject>Disease Models, Animal</subject><subject>Dwarfism</subject><subject>Endocrinology and metabolism</subject><subject>Energy metabolism</subject><subject>Female</subject><subject>Fibroblast growth factor receptors</subject><subject>Fibroblasts</subject><subject>Genetic aspects</subject><subject>Glucose</subject><subject>Glucose metabolism</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>High fat diet</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Life Sciences</subject><subject>Lipid Metabolism</subject><subject>Male</subject><subject>Medical innovations</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchymal Stem Cells</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Mutation</subject><subject>Normalizing</subject><subject>Obesity</subject><subject>Obesity - etiology</subject><subject>Obesity - prevention & control</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>People and Places</subject><subject>Phosphatase</subject><subject>Receptor, Fibroblast Growth Factor, Type 3</subject><subject>Receptor, Fibroblast Growth Factor, Type 3 - pharmacology</subject><subject>Receptor, Fibroblast Growth Factor, Type 3 - therapeutic use</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Sabatier, Paul (1854-1941)</subject><subject>Santé publique et épidémiologie</subject><subject>Secondary Prevention</subject><subject>Stem cells</subject><subject>Therapy</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11r2zAUhs3YWLtu_2BshsFYL5Lp2_bNIJSmDRQK3cetkCU5VlAsV1LC8u8nN25JSi-GL2zOec57fF7pZNlHCKYQF_D7ym18J-y0d52eAljRsmCvslNYYTRhCODXB98n2bsQVgBQXDL2NjtBFaOoAvA0U5fC213euxA7EYXNg7Ob2up8fjW_w3lstRd9ynu91V0MQyAXcdcbmViVgtb165TJXZO7WgcTd7npciFb1ynveiuCEe-zN42wQX8Y32fZ7_nlr4vryc3t1eJidjORRYXiBEFIFSFEVkoAUuCyVJCKkhAMNWIlgUTVRNGGaaRYLdPMqJBQEV0oIauEnWWf97q9dYGPBgWOACJFxWBVJGKxJ5QTK957sxZ-x50w_CHg_JILH420mmOqJGMNTj6VBJSsrJnUsKpp6iWQVEnrx9htU6-1kskFL-yR6HGmMy1fui2nZZXOCiWB871A-6zsenbDhxggpGIFoFuY2G9jM-_uNzpEvjZBamtFp93mYUaKEUR0QL88Q192YqSWIg1rusalf5SDKJ9RTGhRlAAnavoClR6l10amm9eYFD8qOD8qSEzUf-NSbELgi593_8_e_jlmvx6wrRY2tsNVjcZ14Rgke1B6F4LXzZOzEPBhcR7d4MPi8HFxUtmnw8N8KnrcFPwPO-4SEQ</recordid><startdate>20180413</startdate><enddate>20180413</enddate><creator>Saint-Laurent, Celine</creator><creator>Garcia, Stephanie</creator><creator>Sarrazy, Vincent</creator><creator>Dumas, Karine</creator><creator>Authier, Florence</creator><creator>Sore, Sophie</creator><creator>Tran, Albert</creator><creator>Gual, Philippe</creator><creator>Gennero, Isabelle</creator><creator>Salles, Jean-Pierre</creator><creator>Gouze, Elvire</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20180413</creationdate><title>Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia</title><author>Saint-Laurent, Celine ; Garcia, Stephanie ; Sarrazy, Vincent ; Dumas, Karine ; Authier, Florence ; Sore, Sophie ; Tran, Albert ; Gual, Philippe ; Gennero, Isabelle ; Salles, Jean-Pierre ; Gouze, Elvire</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c792t-2115d444c9da047388d15a84431e268414db4d5f6e2d6bc01927c1d4e7dac9443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Achondroplasia</topic><topic>Achondroplasia - complications</topic><topic>Achondroplasia - diagnosis</topic><topic>Achondroplasia - drug therapy</topic><topic>Achondroplasia - genetics</topic><topic>Adipose tissue</topic><topic>Adolescent</topic><topic>Age</topic><topic>Animal models</topic><topic>Animal tissues</topic><topic>Animals</topic><topic>Anthropometry</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Blood Glucose</topic><topic>Bone growth</topic><topic>Cardiovascular diseases</topic><topic>Care and treatment</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Complications</topic><topic>Complications and side effects</topic><topic>Densitometers</topic><topic>Deregulation</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Disease</topic><topic>Disease Models, Animal</topic><topic>Dwarfism</topic><topic>Endocrinology and metabolism</topic><topic>Energy metabolism</topic><topic>Female</topic><topic>Fibroblast growth factor receptors</topic><topic>Fibroblasts</topic><topic>Genetic aspects</topic><topic>Glucose</topic><topic>Glucose metabolism</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Health risks</topic><topic>High fat diet</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Life Sciences</topic><topic>Lipid Metabolism</topic><topic>Male</topic><topic>Medical innovations</topic><topic>Medicine and Health Sciences</topic><topic>Mesenchymal Stem Cells</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Mutation</topic><topic>Normalizing</topic><topic>Obesity</topic><topic>Obesity - etiology</topic><topic>Obesity - prevention & control</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>People and Places</topic><topic>Phosphatase</topic><topic>Receptor, Fibroblast Growth Factor, Type 3</topic><topic>Receptor, Fibroblast Growth Factor, Type 3 - pharmacology</topic><topic>Receptor, Fibroblast Growth Factor, Type 3 - therapeutic use</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Sabatier, Paul (1854-1941)</topic><topic>Santé publique et épidémiologie</topic><topic>Secondary Prevention</topic><topic>Stem cells</topic><topic>Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saint-Laurent, Celine</creatorcontrib><creatorcontrib>Garcia, Stephanie</creatorcontrib><creatorcontrib>Sarrazy, Vincent</creatorcontrib><creatorcontrib>Dumas, Karine</creatorcontrib><creatorcontrib>Authier, Florence</creatorcontrib><creatorcontrib>Sore, Sophie</creatorcontrib><creatorcontrib>Tran, Albert</creatorcontrib><creatorcontrib>Gual, Philippe</creatorcontrib><creatorcontrib>Gennero, Isabelle</creatorcontrib><creatorcontrib>Salles, Jean-Pierre</creatorcontrib><creatorcontrib>Gouze, Elvire</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saint-Laurent, Celine</au><au>Garcia, Stephanie</au><au>Sarrazy, Vincent</au><au>Dumas, Karine</au><au>Authier, Florence</au><au>Sore, Sophie</au><au>Tran, Albert</au><au>Gual, Philippe</au><au>Gennero, Isabelle</au><au>Salles, Jean-Pierre</au><au>Gouze, Elvire</au><au>Bader, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-04-13</date><risdate>2018</risdate><volume>13</volume><issue>4</issue><spage>e0195876</spage><epage>e0195876</epage><pages>e0195876-e0195876</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients, and is associated to life-threatening complications including increasing risk of cardiovascular pathologies. We have thus decided to study obesity in patients and to use the mouse model to evaluate if soluble FGFR3 therapy, an innovative treatment approach for achondroplasia, could also impact the development of this significant complication.
To achieve this, we have first fully characterized the metabolic deregulations in these patients by conducting a longitudinal retrospective study, in children with achondroplasia Anthropometric, densitometric measures as well as several blood parameters were recorded and compared between three age groups ranging from [0-3], [4-8] and [9-18] years old. Our results show unexpected results with the development of an atypical obesity with preferential fat deposition in the abdomen that is remarkably not associated with classical complications of obesity such as diabetes or hypercholosterolemia. Because it is not associated with diabetes, the atypical obesity has not been studied in the past even though it is recognized as a real problem in these patients. These results were validated in a murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was observed. Unexpected alterations in glucose metabolism were highlighted during high-fat diet. Glucose, insulin or lipid levels remained low, without the development of diabetes. Very interestingly, in achondroplasia mice treated with soluble FGFR3 during the growth period (from D3 to D22), the development of these metabolic deregulations was prevented in adult animals (between 4 and 14 weeks of age). The lean-over-fat tissues ratio was restored and glucose metabolism showed normal levels. Treating Fgfr3ach/+ mice with soluble FGFR3 during the growth period, prevented the development of these metabolic deregulations in adult animals and restored lean-over-fat tissues ratio as well as glucose metabolism in adult animals.
This study demonstrate that achondroplasia patients develop an atypical obesity with preferential abdominal obesity not associated with classical complications. These results suggest that achondroplasia induces an uncommon metabolism of energy, directly linked to the FGFR3 mutation. These data strongly suggest that this common complication of achondroplasia should be included in the clinical management of patients. In this context, sFGFR3 proved to be a promising treatment for achondroplasia by normalizing the biology at different levels, not only restoring bone growth but also preventing the atypical visceral obesity and some metabolic deregulations.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29652901</pmid><doi>10.1371/journal.pone.0195876</doi><tpages>e0195876</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-04, Vol.13 (4), p.e0195876-e0195876 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2024796197 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Achondroplasia Achondroplasia - complications Achondroplasia - diagnosis Achondroplasia - drug therapy Achondroplasia - genetics Adipose tissue Adolescent Age Animal models Animal tissues Animals Anthropometry Biology and Life Sciences Biomarkers Blood Glucose Bone growth Cardiovascular diseases Care and treatment Child Child, Preschool Children Complications Complications and side effects Densitometers Deregulation Diabetes Diabetes mellitus Disease Disease Models, Animal Dwarfism Endocrinology and metabolism Energy metabolism Female Fibroblast growth factor receptors Fibroblasts Genetic aspects Glucose Glucose metabolism Growth factors Health aspects Health risks High fat diet Human health and pathology Humans Infant Infant, Newborn Insulin Insulin - metabolism Life Sciences Lipid Metabolism Male Medical innovations Medicine and Health Sciences Mesenchymal Stem Cells Mesenchymal Stromal Cells - metabolism Metabolism Mice Mice, Transgenic Mutation Normalizing Obesity Obesity - etiology Obesity - prevention & control Patients Pediatrics People and Places Phosphatase Receptor, Fibroblast Growth Factor, Type 3 Receptor, Fibroblast Growth Factor, Type 3 - pharmacology Receptor, Fibroblast Growth Factor, Type 3 - therapeutic use Risk factors Rodents Sabatier, Paul (1854-1941) Santé publique et épidémiologie Secondary Prevention Stem cells Therapy |
| title | Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T21%3A15%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Early%20postnatal%20soluble%20FGFR3%20therapy%20prevents%20the%20atypical%20development%20of%20obesity%20in%20achondroplasia&rft.jtitle=PloS%20one&rft.au=Saint-Laurent,%20Celine&rft.date=2018-04-13&rft.volume=13&rft.issue=4&rft.spage=e0195876&rft.epage=e0195876&rft.pages=e0195876-e0195876&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0195876&rft_dat=%3Cgale_plos_%3EA534577803%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2024796197&rft_id=info:pmid/29652901&rft_galeid=A534577803&rft_doaj_id=oai_doaj_org_article_35dc66f3290840868b6ce19b5ac9a2cd&rfr_iscdi=true |