Tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPα

The Journal of Clinical Investigation
Robert C BauerDaniel J Rader

Abstract

Variants near the gene TRIB1 are significantly associated with several plasma lipid traits, circulating liver enzymes, and the development of coronary artery disease in humans; however, it is not clear how its protein product tribbles-1 regulates lipid metabolism. Here, we evaluated mice harboring a liver-specific deletion of Trib1 (Trib1_LSKO) to elucidate the role of tribbles-1 in mammalian hepatic lipid metabolism. These mice exhibited increased hepatic triglyceride (TG) content, lipogenic gene transcription, and de novo lipogenesis. Microarray analysis revealed altered transcription of genes that are downstream of the transcription factor C/EBPα, and Trib1_LSKO mice had increased hepatic C/EBPα protein. Hepatic overexpression of C/EBPα in WT mice phenocopied Trib1_LSKO livers, and hepatic knockout of Cebpa in Trib1_LSKO mice revealed that C/EBPα is required for the increased lipogenesis. Using ChIP-Seq, we found that Trib1_LSKO mice had increased DNA-bound C/EBPα near lipogenic genes and the Trib1 gene, which itself was transcriptionally upregulated by C/EBPα overexpression. Together, our results reveal that tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPα, which in turn transcriptio...Continue Reading

References

Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER
Aug 27, 2004·Obesity Surgery·Francesco Saverio PapadiaNicola Scopinaro
Jun 24, 2006·Science·Ling QiMarc Montminy
Nov 14, 2006·Cancer Cell·Karen KeeshanWarren S Pear
Jan 15, 2008·Nature Genetics·Cristen J WillerGonçalo R Abecasis
Apr 26, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Francesco AndreozziGiorgio Sesti
Sep 9, 2008·Cell·Carla B GreenJoseph Bass
Nov 5, 2008·Genes & Development·Martina I LefterovaMitchell A Lazar
Apr 4, 2009·PLoS Genetics·Michael E HughesJohn B Hogenesch
Aug 20, 2009·Bioinformatics·Hyunjin ShinX Shirley Liu
Oct 9, 2009·The Biochemical Journal·Victoria A PayneJustin J Rochford
Jan 19, 2010·Annual Review of Pathology·Dina G TiniakosElizabeth M Brunt
May 4, 2010·Nature Biotechnology·Cory Y McLeanGill Bejerano
May 19, 2010·Genes & Development·David J StegerMitchell A Lazar
Aug 6, 2010·Nature·Tanya M TeslovichSekar Kathiresan
Nov 19, 2010·The Journal of Clinical Investigation·Ralph BurkhardtDaniel J Rader
Jan 20, 2011·Journal of Lipid Research·Amanda J HooperJohn R Burnett
Dec 4, 2012·Nature Genetics·Panos DeloukasNilesh J Samani
Oct 8, 2013·Nature Genetics·Cristen J WillerUNKNOWN Global Lipids Genetics Consortium
Jan 7, 2014·Journal of Molecular Endocrinology·Yuumi IshizukaUNKNOWN Jichi Medical University Promotion Team of Large-Scale Human Genome Bank for All over Japan

❮ Previous
Next ❯

Citations

Feb 6, 2016·Cardiovascular Drugs and Therapy·Yanhong GuoY Eugene Chen
Mar 19, 2016·Trends in Molecular Medicine·Robert C BauerDaniel J Rader
Mar 29, 2016·PloS One·Sébastien SoubeyrandRuth McPherson
Jun 15, 2018·The Journal of Biological Chemistry·Lilli ArndtRalph Burkhardt
Aug 30, 2018·Journal of Developmental Origins of Health and Disease·M DesaiM G Ross
Aug 8, 2018·Nucleic Acids Research·Daniel M CohenDavid J Steger
Feb 20, 2016·Circulation Research·Sylvia T NurnbergDaniel J Rader
Apr 26, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Kavita S Jadhav, Robert C Bauer
Apr 16, 2019·Current Opinion in Lipidology·Elizabeth E HaRobert C Bauer
Mar 10, 2020·The Journal of Experimental Medicine·Kelly S RomeWarren S Pear
Aug 26, 2020·PloS One·Marina SerperUNKNOWN VA Million Veteran Program
Sep 12, 2020·Circulation Research·Xin BiDaniel J Rader
Nov 1, 2015·Biochemical Society Transactions·Robert C BauerDaniel J Rader
Jun 9, 2018·Hepatology Communications·Eiko SaijouAtsushi Miyajima
Jan 1, 2016·Current Genetic Medicine Reports·Jacqueline S Dron, Robert A Hegele
Sep 17, 2017·Nature Communications·Sean M ArmourMitchell A Lazar
May 25, 2016·The FEBS Journal·Jennie Lin, Kiran Musunuru
Sep 27, 2018·Science Signaling·Sam A JamiesonPeter D Mace
Oct 18, 2019·The FEBS Journal·Laura Richmond, Karen Keeshan
Jul 19, 2017·Scientific Reports·Sébastien SoubeyrandRuth McPherson
Mar 3, 2021·Current Opinion in Lipidology·James A Votava, Brian W Parks
Apr 23, 2021·Current Opinion in Lipidology·Krista Y Hu, Robert C Bauer
Jun 23, 2021·Clinical and Translational Science·Deepti AbbeyDaniel J Rader
Oct 7, 2021·Phytotherapy Research : PTR·Dhananjay GireSaroj Ghaskadbi
Nov 16, 2021·The Journal of Clinical Investigation·Katherine Quiroz-FigueroaDaniel J Rader

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE70848

Methods Mentioned

BETA
PCR
ChIP-Seq
ubiquitination
ChIP

Software Mentioned

HOMER
CEAS
GREAT

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Cold Spring Harbor Symposia on Quantitative Biology
Z SunM A Lazar
Journal of Molecular Endocrinology
Yuumi IshizukaJichi Medical University Promotion Team of Large-Scale Human Genome Bank for All over Japan
© 2021 Meta ULC. All rights reserved