Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner
Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring. C57BL/6J female mice were provid...
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| Veröffentlicht in: | International journal of molecular sciences 2021-07, Vol.22 (15), p.8104 |
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| creator | Schoonejans, Josca M Blackmore, Heather L Ashmore, Thomas J Aiken, Catherine E Fernandez-Twinn, Denise S Ozanne, Susan E |
| description | Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring.
C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR.
Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (
< 0.05), exaggerated adipocyte hyperplasia (
< 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (
< 0.05) and the mRNA expression of
(
< 0.05). These changes were not observed in female Ob-Met offspring.
Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT. |
| doi_str_mv | 10.3390/ijms22158104 |
| format | Article |
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C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR.
Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (
< 0.05), exaggerated adipocyte hyperplasia (
< 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (
< 0.05) and the mRNA expression of
(
< 0.05). These changes were not observed in female Ob-Met offspring.
Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22158104</identifier><identifier>PMID: 34360870</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adipocytes ; Adipose tissue ; Adiposity ; Age ; Animals ; Animals, Newborn - metabolism ; Antidiabetics ; Body weight ; Diabetes ; Diabetes mellitus ; Diabetes, Gestational - drug therapy ; Diabetes, Gestational - metabolism ; Female ; Females ; Gene expression ; Gestation ; Glucose ; Histology ; Hyperplasia ; Hypertrophy ; Inflammation ; Insulin resistance ; Intervention ; Investigations ; Macrophages ; Male ; Metabolism ; Metformin ; Metformin - pharmacology ; Mice ; Mice, Inbred C57BL ; Obesity ; Obesity, Maternal - drug therapy ; Obesity, Maternal - metabolism ; Polymerase chain reaction ; Pregnancy ; Prenatal experience ; Prenatal Exposure Delayed Effects - metabolism ; Prenatal Exposure Delayed Effects - pathology ; Sex Factors ; Womens health ; Young adults</subject><ispartof>International journal of molecular sciences, 2021-07, Vol.22 (15), p.8104</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-7854ae3196320782e90c90cfbf1fdedde66684092942ff5780e9a695f1539c3d3</citedby><cites>FETCH-LOGICAL-c412t-7854ae3196320782e90c90cfbf1fdedde66684092942ff5780e9a695f1539c3d3</cites><orcidid>0000-0003-2610-277X ; 0000-0001-8753-5144 ; 0000-0003-2893-7199 ; 0000-0003-0180-3852</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347264/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347264/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34360870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schoonejans, Josca M</creatorcontrib><creatorcontrib>Blackmore, Heather L</creatorcontrib><creatorcontrib>Ashmore, Thomas J</creatorcontrib><creatorcontrib>Aiken, Catherine E</creatorcontrib><creatorcontrib>Fernandez-Twinn, Denise S</creatorcontrib><creatorcontrib>Ozanne, Susan E</creatorcontrib><title>Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring.
C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR.
Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (
< 0.05), exaggerated adipocyte hyperplasia (
< 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (
< 0.05) and the mRNA expression of
(
< 0.05). These changes were not observed in female Ob-Met offspring.
Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT.</description><subject>Adipocytes</subject><subject>Adipose tissue</subject><subject>Adiposity</subject><subject>Age</subject><subject>Animals</subject><subject>Animals, Newborn - metabolism</subject><subject>Antidiabetics</subject><subject>Body weight</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes, Gestational - drug therapy</subject><subject>Diabetes, Gestational - metabolism</subject><subject>Female</subject><subject>Females</subject><subject>Gene expression</subject><subject>Gestation</subject><subject>Glucose</subject><subject>Histology</subject><subject>Hyperplasia</subject><subject>Hypertrophy</subject><subject>Inflammation</subject><subject>Insulin resistance</subject><subject>Intervention</subject><subject>Investigations</subject><subject>Macrophages</subject><subject>Male</subject><subject>Metabolism</subject><subject>Metformin</subject><subject>Metformin - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Obesity</subject><subject>Obesity, Maternal - drug therapy</subject><subject>Obesity, Maternal - metabolism</subject><subject>Polymerase chain reaction</subject><subject>Pregnancy</subject><subject>Prenatal experience</subject><subject>Prenatal Exposure Delayed Effects - metabolism</subject><subject>Prenatal Exposure Delayed Effects - pathology</subject><subject>Sex Factors</subject><subject>Womens health</subject><subject>Young adults</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkV1rFDEUhoMotlbvvJaAN150NF-TSW6Epdha6LJC9cKrIZs5WbPMJGuSKe7v8A-bflhWIZCQ8-ThvDkIvabkPeeafPDbKTNGW0WJeIKOqWCsIUR2Tw_OR-hFzltCGGetfo6OuOCSqI4co99LUyAFM-IlFBfT5AO-DPXqBkLxMeBhTj5s8GoNGfDFONuYoalEHCGZUPCXBJtggt3jhXNgS8aLwe9i9mWPq-t7nOvrxTCPBS_jXB0r5_LuzlnLBl_Dr-Z6B9Y7b_HShADpJXrmzJjh1cN-gr6df_p69rm5Wl1cni2uGisoK02nWmGAUy05I51ioImty60ddQMMA0gplSCaacGcaztFQBupW0dbri0f-An6eO_dzesJBlsTJzP2tbnJpH0fje__rQT_o9_Em15x0TEpquDdgyDFnzPk0k8-WxhHE6Bm7VnbasGZ0ryib_9Dt3G-_fc7SikuBWkrdXpP2RRzTuAem6Gkv512fzjtir85DPAI_x0v_wO0hqhL</recordid><startdate>20210728</startdate><enddate>20210728</enddate><creator>Schoonejans, Josca M</creator><creator>Blackmore, Heather L</creator><creator>Ashmore, Thomas J</creator><creator>Aiken, Catherine E</creator><creator>Fernandez-Twinn, Denise S</creator><creator>Ozanne, Susan E</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2610-277X</orcidid><orcidid>https://orcid.org/0000-0001-8753-5144</orcidid><orcidid>https://orcid.org/0000-0003-2893-7199</orcidid><orcidid>https://orcid.org/0000-0003-0180-3852</orcidid></search><sort><creationdate>20210728</creationdate><title>Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner</title><author>Schoonejans, Josca M ; 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This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring.
C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR.
Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (
< 0.05), exaggerated adipocyte hyperplasia (
< 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (
< 0.05) and the mRNA expression of
(
< 0.05). These changes were not observed in female Ob-Met offspring.
Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34360870</pmid><doi>10.3390/ijms22158104</doi><orcidid>https://orcid.org/0000-0003-2610-277X</orcidid><orcidid>https://orcid.org/0000-0001-8753-5144</orcidid><orcidid>https://orcid.org/0000-0003-2893-7199</orcidid><orcidid>https://orcid.org/0000-0003-0180-3852</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2021-07, Vol.22 (15), p.8104 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adipocytes Adipose tissue Adiposity Age Animals Animals, Newborn - metabolism Antidiabetics Body weight Diabetes Diabetes mellitus Diabetes, Gestational - drug therapy Diabetes, Gestational - metabolism Female Females Gene expression Gestation Glucose Histology Hyperplasia Hypertrophy Inflammation Insulin resistance Intervention Investigations Macrophages Male Metabolism Metformin Metformin - pharmacology Mice Mice, Inbred C57BL Obesity Obesity, Maternal - drug therapy Obesity, Maternal - metabolism Polymerase chain reaction Pregnancy Prenatal experience Prenatal Exposure Delayed Effects - metabolism Prenatal Exposure Delayed Effects - pathology Sex Factors Womens health Young adults |
| title | Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner |
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