Cargando…
Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice
OBJECTIVE: Multiple genome-wide association studies (GWAS) have identified SNPs in the 8q24 locus near TRIB1 that are significantly associated with plasma lipids and other markers of cardiometabolic health, and prior studies have revealed the roles of hepatic and myeloid Trib1 in plasma lipid regula...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749272/ https://www.ncbi.nlm.nih.gov/pubmed/34890852 http://dx.doi.org/10.1016/j.molmet.2021.101412 |
_version_ | 1784631189468872704 |
---|---|
author | Ha, Elizabeth E. Quartuccia, Gabriella I. Ling, Ruifeng Xue, Chenyi Karikari, Rhoda A. Hernandez-Ono, Antonio Hu, Krista Y. Matias, Caio V. Imam, Rami Cui, Jian Pellegata, Natalia S. Herzig, Stephan Georgiadi, Anastasia Soni, Rajesh K. Bauer, Robert C. |
author_facet | Ha, Elizabeth E. Quartuccia, Gabriella I. Ling, Ruifeng Xue, Chenyi Karikari, Rhoda A. Hernandez-Ono, Antonio Hu, Krista Y. Matias, Caio V. Imam, Rami Cui, Jian Pellegata, Natalia S. Herzig, Stephan Georgiadi, Anastasia Soni, Rajesh K. Bauer, Robert C. |
author_sort | Ha, Elizabeth E. |
collection | PubMed |
description | OBJECTIVE: Multiple genome-wide association studies (GWAS) have identified SNPs in the 8q24 locus near TRIB1 that are significantly associated with plasma lipids and other markers of cardiometabolic health, and prior studies have revealed the roles of hepatic and myeloid Trib1 in plasma lipid regulation and atherosclerosis. The same 8q24 SNPs are additionally associated with plasma adiponectin levels in humans, implicating TRIB1 in adipocyte biology. Here, we hypothesize that TRIB1 in adipose tissue regulates plasma adiponectin, lipids, and metabolic health. METHODS: We investigate the metabolic phenotype of adipocyte-specific Trib1 knockout mice (Trib1_ASKO) fed on chow and high-fat diet (HFD). Through secretomics of adipose tissue explants and RNA-seq of adipocytes and livers from these mice, we further investigate the mechanism of TRIB1 in adipose tissue. RESULTS: Trib1_ASKO mice have an improved metabolic phenotype with increased plasma adiponectin levels, improved glucose tolerance, and decreased plasma lipids. Trib1_ASKO adipocytes have increased adiponectin production and secretion independent of the known TRIB1 function of regulating proteasomal degradation. RNA-seq analysis of adipocytes and livers from Trib1_ASKO mice indicates that alterations in adipocyte function underlie the observed plasma lipid changes. Adipose tissue explant secretomics further reveals that Trib1_ASKO adipose tissue has decreased ANGPTL4 production, and we demonstrate an accompanying increase in the lipoprotein lipase (LPL) activity that likely underlies the triglyceride phenotype. CONCLUSIONS: This study shows that adipocyte Trib1 regulates multiple aspects of metabolic health, confirming previously observed genetic associations in humans and shedding light on the further mechanisms by which TRIB1 regulates plasma lipids and metabolic health. |
format | Online Article Text |
id | pubmed-8749272 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-87492722022-01-13 Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice Ha, Elizabeth E. Quartuccia, Gabriella I. Ling, Ruifeng Xue, Chenyi Karikari, Rhoda A. Hernandez-Ono, Antonio Hu, Krista Y. Matias, Caio V. Imam, Rami Cui, Jian Pellegata, Natalia S. Herzig, Stephan Georgiadi, Anastasia Soni, Rajesh K. Bauer, Robert C. Mol Metab Original Article OBJECTIVE: Multiple genome-wide association studies (GWAS) have identified SNPs in the 8q24 locus near TRIB1 that are significantly associated with plasma lipids and other markers of cardiometabolic health, and prior studies have revealed the roles of hepatic and myeloid Trib1 in plasma lipid regulation and atherosclerosis. The same 8q24 SNPs are additionally associated with plasma adiponectin levels in humans, implicating TRIB1 in adipocyte biology. Here, we hypothesize that TRIB1 in adipose tissue regulates plasma adiponectin, lipids, and metabolic health. METHODS: We investigate the metabolic phenotype of adipocyte-specific Trib1 knockout mice (Trib1_ASKO) fed on chow and high-fat diet (HFD). Through secretomics of adipose tissue explants and RNA-seq of adipocytes and livers from these mice, we further investigate the mechanism of TRIB1 in adipose tissue. RESULTS: Trib1_ASKO mice have an improved metabolic phenotype with increased plasma adiponectin levels, improved glucose tolerance, and decreased plasma lipids. Trib1_ASKO adipocytes have increased adiponectin production and secretion independent of the known TRIB1 function of regulating proteasomal degradation. RNA-seq analysis of adipocytes and livers from Trib1_ASKO mice indicates that alterations in adipocyte function underlie the observed plasma lipid changes. Adipose tissue explant secretomics further reveals that Trib1_ASKO adipose tissue has decreased ANGPTL4 production, and we demonstrate an accompanying increase in the lipoprotein lipase (LPL) activity that likely underlies the triglyceride phenotype. CONCLUSIONS: This study shows that adipocyte Trib1 regulates multiple aspects of metabolic health, confirming previously observed genetic associations in humans and shedding light on the further mechanisms by which TRIB1 regulates plasma lipids and metabolic health. Elsevier 2021-12-07 /pmc/articles/PMC8749272/ /pubmed/34890852 http://dx.doi.org/10.1016/j.molmet.2021.101412 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Ha, Elizabeth E. Quartuccia, Gabriella I. Ling, Ruifeng Xue, Chenyi Karikari, Rhoda A. Hernandez-Ono, Antonio Hu, Krista Y. Matias, Caio V. Imam, Rami Cui, Jian Pellegata, Natalia S. Herzig, Stephan Georgiadi, Anastasia Soni, Rajesh K. Bauer, Robert C. Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice |
title | Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice |
title_full | Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice |
title_fullStr | Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice |
title_full_unstemmed | Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice |
title_short | Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice |
title_sort | adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749272/ https://www.ncbi.nlm.nih.gov/pubmed/34890852 http://dx.doi.org/10.1016/j.molmet.2021.101412 |
work_keys_str_mv | AT haelizabethe adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT quartucciagabriellai adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT lingruifeng adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT xuechenyi adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT karikarirhodaa adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT hernandezonoantonio adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT hukristay adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT matiascaiov adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT imamrami adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT cuijian adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT pellegatanatalias adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT herzigstephan adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT georgiadianastasia adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT sonirajeshk adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice AT bauerrobertc adipocytespecifictribblespseudokinase1regulatesplasmaadiponectinandplasmalipidsinmice |