MiR-409-3p regulates angiogenesis, white to brown adipose tissue transition, and insulin resistance through MAP4K3 and ZEB1 signaling pathways.
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MiR-409-3p regulates angiogenesis, white to brown adipose tissue transition, and insulin resistance through MAP4K3 and ZEB1 signaling pathways.

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MiR-409-3p regulates angiogenesis, white to brown adipose tissue transition, and insulin resistance through MAP4K3 and ZEB1 signaling pathways.

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dc.contributor.author Becker-Greene, Dakota
dc.contributor.author Li, Hao
dc.contributor.author Pérez Cremades, Daniel
dc.contributor.author Wu, Winona
dc.contributor.author Bestepe, Furkan
dc.contributor.author Ozdemir, Denizhan
dc.contributor.author Niosi, Carolyn E.
dc.contributor.author Aydogan, Ceren
dc.contributor.author Orgill, Dennis P.
dc.contributor.author Feinberg, Mark W.
dc.contributor.author Icli, Basak
dc.date.accessioned 2022-04-04T07:50:36Z
dc.date.available 2022-04-04T07:50:36Z
dc.date.issued 2021
dc.identifier.uri https://hdl.handle.net/10550/82136
dc.description.abstract Endothelial cells (ECs) within the microvasculature of brown adipose tissue (BAT) are important in regulating the plasticity of adipocytes in response to increased metabolic demand by modulating the angiogenic response. However, the mechanism of EC-adipocyte crosstalk during this process is not completely understood. We used RNA sequencing to profile microRNAs derived from BAT ECs of obese mice and identified an anti-angiogenic microRNA, miR-409-3p. MiR-409-3p overexpres- sion inhibited EC angiogenic properties; whereas, its inhibition had the opposite effects. Mechanistic studies revealed that miR-409-3p targets ZEB1 and MAP4K3. Knockdown of ZEB1/MAP4K3 phenocopied the angiogenic effects of miR-409-3p. Adipocytes co-cultured with conditioned media from ECs deficient in miR-409-3p showed increased expression of BAT markers, UCP1 and CIDEA. We identified a pro-angiogenic growth factor, placental growth factor (PLGF), released from ECs in response to miR-409-3p inhibition. Deficiency of ZEB1 or MAP4K3 blocked the release of PLGF from ECs and PLGF stimulation of 3T3-L1 adipocytes increased UCP1 expression in a miR-409-3p dependent manner. MiR-409-3p neutraliza- tion improved BAT angiogenesis, glucose and insulin tolerance, and energy expenditure in mice with diet-induced obesity. These findings establish miR-409-3p as a critical regulator of EC-BAT crosstalk by modulating a ZEB1-MAP4K3-PLGF signaling axis, providing new insights for therapeutic intervention in obesity.
dc.language.iso eng
dc.relation.ispartof Cellular and Molecular Life Sciences, 2021, vol. 78, p. 7663-7679
dc.rights.uri info:eu-repo/semantics/openAccess
dc.source Becker-Greene, Dakota Li, Hao Pérez Cremades, Daniel Wu, Winona Bestepe, Furkan Ozdemir, Denizhan Niosi, Carolyn E. Aydogan, Ceren Orgill, Dennis P. Feinberg, Mark W. Icli, Basak 2021 MiR-409-3p regulates angiogenesis, white to brown adipose tissue transition, and insulin resistance through MAP4K3 and ZEB1 signaling pathways. Cellular and Molecular Life Sciences 78 7663 7679
dc.subject Fisiologia
dc.title MiR-409-3p regulates angiogenesis, white to brown adipose tissue transition, and insulin resistance through MAP4K3 and ZEB1 signaling pathways.
dc.type info:eu-repo/semantics/article
dc.date.updated 2022-04-04T07:50:36Z
dc.identifier.idgrec 151052

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