Inhibitor of Differentiation-3 Mediates High Fat Diet-Induced Visceral Fat Expansion
OBJECTIVE—Inhibitor of differentiation-3 (Id3) has been implicated in promoting angiogenesis, a key determinant of high-fat diet (HFD)-induced visceral adiposity. Yet the role of Id3 in HFD-induced angiogenesis and visceral adipose expansion is unknown. METHODS AND RESULTS—Id3 mice demonstrated a si...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2012-02, Vol.32 (2), p.317-324 |
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| container_title | Arteriosclerosis, thrombosis, and vascular biology |
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| creator | Cutchins, Alexis Harmon, Daniel B Kirby, Jennifer L Doran, Amanda C Oldham, Stephanie N Skaflen, Marcus Klibanov, Alexander L Meller, Nahum Keller, Susanna R Garmey, James McNamara, Coleen A |
| description | OBJECTIVE—Inhibitor of differentiation-3 (Id3) has been implicated in promoting angiogenesis, a key determinant of high-fat diet (HFD)-induced visceral adiposity. Yet the role of Id3 in HFD-induced angiogenesis and visceral adipose expansion is unknown.
METHODS AND RESULTS—Id3 mice demonstrated a significant attenuation of HFD-induced visceral fat depot expansion compared to wild type littermate controls. Importantly, unlike other Id proteins, loss of Id3 did not affect adipose depot size in young mice fed chow diet or differentiation of adipocytes in vitro or in vivo. Contrast enhanced ultrasound revealed a significant attenuation of visceral fat microvascular blood volume in HFD-fed mice null for Id3 compared to wild type controls. HFD induced Id3 and VEGFA expression in the visceral stromal vascular fraction and Id3 mice had significantly lower levels of VEGFA protein in visceral adipose tissue compared to wild type. Furthermore, HFD-induced VEGFA expression in visceral adipose tissue was completely abolished by loss of Id3. Consistent with this effect, Id3 abolished E12-mediated repression of VEGFA promoter activity.
CONCLUSION—Results identify Id3 as an important regulator of HFD-induced visceral adipose VEGFA expression, microvascular blood volume, and depot expansion. Inhibition of Id3 may have potential as a therapeutic strategy to limit visceral adiposity. |
| doi_str_mv | 10.1161/ATVBAHA.111.234856 |
| format | Article |
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METHODS AND RESULTS—Id3 mice demonstrated a significant attenuation of HFD-induced visceral fat depot expansion compared to wild type littermate controls. Importantly, unlike other Id proteins, loss of Id3 did not affect adipose depot size in young mice fed chow diet or differentiation of adipocytes in vitro or in vivo. Contrast enhanced ultrasound revealed a significant attenuation of visceral fat microvascular blood volume in HFD-fed mice null for Id3 compared to wild type controls. HFD induced Id3 and VEGFA expression in the visceral stromal vascular fraction and Id3 mice had significantly lower levels of VEGFA protein in visceral adipose tissue compared to wild type. Furthermore, HFD-induced VEGFA expression in visceral adipose tissue was completely abolished by loss of Id3. Consistent with this effect, Id3 abolished E12-mediated repression of VEGFA promoter activity.
CONCLUSION—Results identify Id3 as an important regulator of HFD-induced visceral adipose VEGFA expression, microvascular blood volume, and depot expansion. Inhibition of Id3 may have potential as a therapeutic strategy to limit visceral adiposity.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.111.234856</identifier><identifier>PMID: 22075252</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Adipocytes - pathology ; Adiposity - physiology ; Animals ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Volume - physiology ; Cardiology. Vascular system ; Dietary Fats - pharmacology ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Drug toxicity and drugs side effects treatment ; Inhibitor of Differentiation Proteins - deficiency ; Inhibitor of Differentiation Proteins - genetics ; Inhibitor of Differentiation Proteins - metabolism ; Intra-Abdominal Fat - blood supply ; Intra-Abdominal Fat - metabolism ; Intra-Abdominal Fat - pathology ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Animal ; Neovascularization, Physiologic - physiology ; Pharmacology. Drug treatments ; Signal Transduction - physiology ; Toxicity: blood ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2012-02, Vol.32 (2), p.317-324</ispartof><rights>2012 American Heart Association, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4762-a64694905fb7d886e5e4e712b78359b455d30eaf34835e8e1a655e563267fedb3</citedby><cites>FETCH-LOGICAL-c4762-a64694905fb7d886e5e4e712b78359b455d30eaf34835e8e1a655e563267fedb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25489180$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22075252$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cutchins, Alexis</creatorcontrib><creatorcontrib>Harmon, Daniel B</creatorcontrib><creatorcontrib>Kirby, Jennifer L</creatorcontrib><creatorcontrib>Doran, Amanda C</creatorcontrib><creatorcontrib>Oldham, Stephanie N</creatorcontrib><creatorcontrib>Skaflen, Marcus</creatorcontrib><creatorcontrib>Klibanov, Alexander L</creatorcontrib><creatorcontrib>Meller, Nahum</creatorcontrib><creatorcontrib>Keller, Susanna R</creatorcontrib><creatorcontrib>Garmey, James</creatorcontrib><creatorcontrib>McNamara, Coleen A</creatorcontrib><title>Inhibitor of Differentiation-3 Mediates High Fat Diet-Induced Visceral Fat Expansion</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—Inhibitor of differentiation-3 (Id3) has been implicated in promoting angiogenesis, a key determinant of high-fat diet (HFD)-induced visceral adiposity. Yet the role of Id3 in HFD-induced angiogenesis and visceral adipose expansion is unknown.
METHODS AND RESULTS—Id3 mice demonstrated a significant attenuation of HFD-induced visceral fat depot expansion compared to wild type littermate controls. Importantly, unlike other Id proteins, loss of Id3 did not affect adipose depot size in young mice fed chow diet or differentiation of adipocytes in vitro or in vivo. Contrast enhanced ultrasound revealed a significant attenuation of visceral fat microvascular blood volume in HFD-fed mice null for Id3 compared to wild type controls. HFD induced Id3 and VEGFA expression in the visceral stromal vascular fraction and Id3 mice had significantly lower levels of VEGFA protein in visceral adipose tissue compared to wild type. Furthermore, HFD-induced VEGFA expression in visceral adipose tissue was completely abolished by loss of Id3. Consistent with this effect, Id3 abolished E12-mediated repression of VEGFA promoter activity.
CONCLUSION—Results identify Id3 as an important regulator of HFD-induced visceral adipose VEGFA expression, microvascular blood volume, and depot expansion. Inhibition of Id3 may have potential as a therapeutic strategy to limit visceral adiposity.</description><subject>Adipocytes - pathology</subject><subject>Adiposity - physiology</subject><subject>Animals</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood Volume - physiology</subject><subject>Cardiology. Vascular system</subject><subject>Dietary Fats - pharmacology</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Inhibitor of Differentiation Proteins - deficiency</subject><subject>Inhibitor of Differentiation Proteins - genetics</subject><subject>Inhibitor of Differentiation Proteins - metabolism</subject><subject>Intra-Abdominal Fat - blood supply</subject><subject>Intra-Abdominal Fat - metabolism</subject><subject>Intra-Abdominal Fat - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Models, Animal</subject><subject>Neovascularization, Physiologic - physiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Signal Transduction - physiology</subject><subject>Toxicity: blood</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1v1DAQhiMEoqXwBzigXBAnF387uSBtS9tdqYjL0qvlJOPGkI0XO6Hw75llt6U92J6Rn3k947co3jJ6yphmHxfrm7PFcoEJO-VCVko_K46Z4pJILfRzjKmpidKSHxWvcv5OKZWc05fFEe5GccWPi_Vq7EMTppjK6MvPwXtIME7BTSGORJRfoMMYcrkMt3156SZkYCKrsZtb6MqbkFtIbvh3c_F768aMda-LF94NGd4czpPi2-XF-nxJrr9erc4X16SVRnPitNS1rKnyjemqSoMCCYbxxlRC1Y1UqhMUnMfRhIIKmNNKgdKCa-Oha8RJ8Wmvu52bDXQtNo692G0KG5f-2OiCfXozht7exl8WFTijNQp8OAik-HOGPNnNbqBhcCPEOduaGaZqqg2SfE-2KeacwD-8wqjduWEPbmDC7N4NLHr3uL-HkvvvR-D9AXC5dYNPbmxD_s8pWdWsosjJPXcXhwlS_jHMd5BsD26YervzVWiqCKeMU44pwcW5-At3dKIL</recordid><startdate>201202</startdate><enddate>201202</enddate><creator>Cutchins, Alexis</creator><creator>Harmon, Daniel B</creator><creator>Kirby, Jennifer L</creator><creator>Doran, Amanda C</creator><creator>Oldham, Stephanie N</creator><creator>Skaflen, Marcus</creator><creator>Klibanov, Alexander L</creator><creator>Meller, Nahum</creator><creator>Keller, Susanna R</creator><creator>Garmey, James</creator><creator>McNamara, Coleen A</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>201202</creationdate><title>Inhibitor of Differentiation-3 Mediates High Fat Diet-Induced Visceral Fat Expansion</title><author>Cutchins, Alexis ; Harmon, Daniel B ; Kirby, Jennifer L ; Doran, Amanda C ; Oldham, Stephanie N ; Skaflen, Marcus ; Klibanov, Alexander L ; Meller, Nahum ; Keller, Susanna R ; Garmey, James ; McNamara, Coleen A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4762-a64694905fb7d886e5e4e712b78359b455d30eaf34835e8e1a655e563267fedb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adipocytes - pathology</topic><topic>Adiposity - physiology</topic><topic>Animals</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood Volume - physiology</topic><topic>Cardiology. Vascular system</topic><topic>Dietary Fats - pharmacology</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Inhibitor of Differentiation Proteins - deficiency</topic><topic>Inhibitor of Differentiation Proteins - genetics</topic><topic>Inhibitor of Differentiation Proteins - metabolism</topic><topic>Intra-Abdominal Fat - blood supply</topic><topic>Intra-Abdominal Fat - metabolism</topic><topic>Intra-Abdominal Fat - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Models, Animal</topic><topic>Neovascularization, Physiologic - physiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Signal Transduction - physiology</topic><topic>Toxicity: blood</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cutchins, Alexis</creatorcontrib><creatorcontrib>Harmon, Daniel B</creatorcontrib><creatorcontrib>Kirby, Jennifer L</creatorcontrib><creatorcontrib>Doran, Amanda C</creatorcontrib><creatorcontrib>Oldham, Stephanie N</creatorcontrib><creatorcontrib>Skaflen, Marcus</creatorcontrib><creatorcontrib>Klibanov, Alexander L</creatorcontrib><creatorcontrib>Meller, Nahum</creatorcontrib><creatorcontrib>Keller, Susanna R</creatorcontrib><creatorcontrib>Garmey, James</creatorcontrib><creatorcontrib>McNamara, Coleen A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cutchins, Alexis</au><au>Harmon, Daniel B</au><au>Kirby, Jennifer L</au><au>Doran, Amanda C</au><au>Oldham, Stephanie N</au><au>Skaflen, Marcus</au><au>Klibanov, Alexander L</au><au>Meller, Nahum</au><au>Keller, Susanna R</au><au>Garmey, James</au><au>McNamara, Coleen A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitor of Differentiation-3 Mediates High Fat Diet-Induced Visceral Fat Expansion</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2012-02</date><risdate>2012</risdate><volume>32</volume><issue>2</issue><spage>317</spage><epage>324</epage><pages>317-324</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>OBJECTIVE—Inhibitor of differentiation-3 (Id3) has been implicated in promoting angiogenesis, a key determinant of high-fat diet (HFD)-induced visceral adiposity. Yet the role of Id3 in HFD-induced angiogenesis and visceral adipose expansion is unknown.
METHODS AND RESULTS—Id3 mice demonstrated a significant attenuation of HFD-induced visceral fat depot expansion compared to wild type littermate controls. Importantly, unlike other Id proteins, loss of Id3 did not affect adipose depot size in young mice fed chow diet or differentiation of adipocytes in vitro or in vivo. Contrast enhanced ultrasound revealed a significant attenuation of visceral fat microvascular blood volume in HFD-fed mice null for Id3 compared to wild type controls. HFD induced Id3 and VEGFA expression in the visceral stromal vascular fraction and Id3 mice had significantly lower levels of VEGFA protein in visceral adipose tissue compared to wild type. Furthermore, HFD-induced VEGFA expression in visceral adipose tissue was completely abolished by loss of Id3. Consistent with this effect, Id3 abolished E12-mediated repression of VEGFA promoter activity.
CONCLUSION—Results identify Id3 as an important regulator of HFD-induced visceral adipose VEGFA expression, microvascular blood volume, and depot expansion. Inhibition of Id3 may have potential as a therapeutic strategy to limit visceral adiposity.</abstract><cop>Philadelphia, PA</cop><pub>American Heart Association, Inc</pub><pmid>22075252</pmid><doi>10.1161/ATVBAHA.111.234856</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes - pathology Adiposity - physiology Animals Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Blood Volume - physiology Cardiology. Vascular system Dietary Fats - pharmacology Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Drug toxicity and drugs side effects treatment Inhibitor of Differentiation Proteins - deficiency Inhibitor of Differentiation Proteins - genetics Inhibitor of Differentiation Proteins - metabolism Intra-Abdominal Fat - blood supply Intra-Abdominal Fat - metabolism Intra-Abdominal Fat - pathology Male Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Models, Animal Neovascularization, Physiologic - physiology Pharmacology. Drug treatments Signal Transduction - physiology Toxicity: blood Vascular Endothelial Growth Factor A - metabolism |
| title | Inhibitor of Differentiation-3 Mediates High Fat Diet-Induced Visceral Fat Expansion |
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