Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue

Abstract Apolipoprotein A4 (APOA4) is one of the most abundant and versatile apolipoproteins facilitating lipid transport and metabolism. APOA4 is synthesized in the small intestine, packaged onto chylomicrons, secreted into intestinal lymph and transported via circulation to several tissues, includ...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jie Qu, Sarah Fourman, Maureen Fitzgerald, Min Liu, Supna Nair, Juan Oses-Prieto, Alma Burlingame, John H. Morris, W. Sean Davidson, Patrick Tso, Aditi Bhargava
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29e9cbef81184dac86a691bd4bd2d354
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:29e9cbef81184dac86a691bd4bd2d354
record_format	dspace
spelling	oai:doaj.org-article:29e9cbef81184dac86a691bd4bd2d3542021-12-02T17:12:25ZLow-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue10.1038/s41598-021-92711-02045-2322https://doaj.org/article/29e9cbef81184dac86a691bd4bd2d3542021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92711-0https://doaj.org/toc/2045-2322Abstract Apolipoprotein A4 (APOA4) is one of the most abundant and versatile apolipoproteins facilitating lipid transport and metabolism. APOA4 is synthesized in the small intestine, packaged onto chylomicrons, secreted into intestinal lymph and transported via circulation to several tissues, including adipose. Since its discovery nearly 4 decades ago, to date, only platelet integrin αIIbβ3 has been identified as APOA4 receptor in the plasma. Using co-immunoprecipitation coupled with mass spectrometry, we probed the APOA4 interactome in mouse gonadal fat tissue, where ApoA4 gene is not transcribed but APOA4 protein is abundant. We demonstrate that lipoprotein receptor-related protein 1 (LRP1) is the cognate receptor for APOA4 in adipose tissue. LRP1 colocalized with APOA4 in adipocytes; it interacted with APOA4 under fasting condition and their interaction was enhanced during lipid feeding concomitant with increased APOA4 levels in plasma. In 3T3-L1 mature adipocytes, APOA4 promoted glucose uptake both in absence and presence of insulin in a dose-dependent manner. Knockdown of LRP1 abrogated APOA4-induced glucose uptake as well as activation of phosphatidylinositol 3 kinase (PI3K)-mediated protein kinase B (AKT). Taken together, we identified LRP1 as a novel receptor for APOA4 in promoting glucose uptake. Considering both APOA4 and LRP1 are multifunctional players in lipid and glucose metabolism, our finding opens up a door to better understand the molecular mechanisms along APOA4-LRP1 axis, whose dysregulation leads to obesity, cardiovascular disease, and diabetes.Jie QuSarah FourmanMaureen FitzgeraldMin LiuSupna NairJuan Oses-PrietoAlma BurlingameJohn H. MorrisW. Sean DavidsonPatrick TsoAditi BhargavaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jie Qu Sarah Fourman Maureen Fitzgerald Min Liu Supna Nair Juan Oses-Prieto Alma Burlingame John H. Morris W. Sean Davidson Patrick Tso Aditi Bhargava Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue
description	Abstract Apolipoprotein A4 (APOA4) is one of the most abundant and versatile apolipoproteins facilitating lipid transport and metabolism. APOA4 is synthesized in the small intestine, packaged onto chylomicrons, secreted into intestinal lymph and transported via circulation to several tissues, including adipose. Since its discovery nearly 4 decades ago, to date, only platelet integrin αIIbβ3 has been identified as APOA4 receptor in the plasma. Using co-immunoprecipitation coupled with mass spectrometry, we probed the APOA4 interactome in mouse gonadal fat tissue, where ApoA4 gene is not transcribed but APOA4 protein is abundant. We demonstrate that lipoprotein receptor-related protein 1 (LRP1) is the cognate receptor for APOA4 in adipose tissue. LRP1 colocalized with APOA4 in adipocytes; it interacted with APOA4 under fasting condition and their interaction was enhanced during lipid feeding concomitant with increased APOA4 levels in plasma. In 3T3-L1 mature adipocytes, APOA4 promoted glucose uptake both in absence and presence of insulin in a dose-dependent manner. Knockdown of LRP1 abrogated APOA4-induced glucose uptake as well as activation of phosphatidylinositol 3 kinase (PI3K)-mediated protein kinase B (AKT). Taken together, we identified LRP1 as a novel receptor for APOA4 in promoting glucose uptake. Considering both APOA4 and LRP1 are multifunctional players in lipid and glucose metabolism, our finding opens up a door to better understand the molecular mechanisms along APOA4-LRP1 axis, whose dysregulation leads to obesity, cardiovascular disease, and diabetes.
format	article
author	Jie Qu Sarah Fourman Maureen Fitzgerald Min Liu Supna Nair Juan Oses-Prieto Alma Burlingame John H. Morris W. Sean Davidson Patrick Tso Aditi Bhargava
author_facet	Jie Qu Sarah Fourman Maureen Fitzgerald Min Liu Supna Nair Juan Oses-Prieto Alma Burlingame John H. Morris W. Sean Davidson Patrick Tso Aditi Bhargava
author_sort	Jie Qu
title	Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue
title_short	Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue
title_full	Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue
title_fullStr	Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue
title_full_unstemmed	Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue
title_sort	low-density lipoprotein receptor-related protein 1 (lrp1) is a novel receptor for apolipoprotein a4 (apoa4) in adipose tissue
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/29e9cbef81184dac86a691bd4bd2d354
work_keys_str_mv	AT jiequ lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT sarahfourman lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT maureenfitzgerald lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT minliu lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT supnanair lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT juanosesprieto lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT almaburlingame lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT johnhmorris lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT wseandavidson lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT patricktso lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue AT aditibhargava lowdensitylipoproteinreceptorrelatedprotein1lrp1isanovelreceptorforapolipoproteina4apoa4inadiposetissue
_version_	1718381368021352448

Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue

Ejemplares similares