Article ; Online: Novel functions of Tribbles-homolog 1 in liver, adipocytes and atherosclerosis.
2024 Volume 35, Issue 2, Page(s) 51–57
Abstract: Purpose of review: Human genetics studies have sparked great interest in the pseudokinase Tribbles homolog 1, as variant at the TRIB1 gene locus were robustly linked to several cardiometabolic traits, including plasma lipids and coronary artery disease. ...
| Abstract | Purpose of review: Human genetics studies have sparked great interest in the pseudokinase Tribbles homolog 1, as variant at the TRIB1 gene locus were robustly linked to several cardiometabolic traits, including plasma lipids and coronary artery disease. In this review, we summarize recent findings from mouse models that investigated the function of hepatic and adipocyte Trib1 in lipid metabolism and its role in atherosclerosis. Recent findings: Studies in atherosclerosis prone low-density lipoprotein (LDL)-receptor knockout mice suggested that systemic Trib1 -deficiency promotes atherosclerotic lesion formation through the modulation of plasma lipids and inflammation. Further, investigations in mice with hepatocyte specific deletion of Trib1 identified a novel role in the catabolism of apoB-containing lipoproteins via regulation of the LDL-receptor. Moreover, recent studies on Trib1 in adipocytes uncovered critical functions in adipose tissue biology, including the regulation of plasma lipid and adiponectin levels and the response to β3-adrenergic receptor activation. Summary: Functional studies in mice have expanded our understanding of how Trib1 contributes to various aspects of cardiometabolic diseases. They support the notion that Trib1 exerts tissue-specific effects, which can result in opposing effects on cardiometabolic traits. Additional studies are required to fully elucidate the molecular mechanisms underlying the cellular and systemic effects of Trib1 . |
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| MeSH term(s) | Humans ; Mice ; Animals ; Liver/metabolism ; Coronary Artery Disease/genetics ; Lipoproteins/metabolism ; Atherosclerosis/genetics ; Atherosclerosis/metabolism ; Adipocytes ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Intracellular Signaling Peptides and Proteins/metabolism |
| Chemical Substances | Lipoproteins ; TRIB1 protein, human ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Intracellular Signaling Peptides and Proteins ; Trib1 protein, mouse |
| Language | English |
| Publishing date | 2024-01-17 |
| Publishing country | England |
| Document type | Review ; Journal Article |
| ZDB-ID | 1045394-5 |
| ISSN | 1473-6535 ; 0957-9672 |
| ISSN (online) | 1473-6535 |
| ISSN | 0957-9672 |
| DOI | 10.1097/MOL.0000000000000917 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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