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Series GSE155973 Query DataSets for GSE155973
Status Public on Dec 07, 2020
Title Macrophage-derived thrombospondin1 promotes obesity-associated non-alcoholic fatty liver disease
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. Previously we have shown that TSP1 plays an important role in obesity-associated metabolic complications including inflammation, insulin resistance, cardiovascular and renal disease. However, its contribution to obesity-associated non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) remains largely unknown and is determined in this study. High fat diet or AMLN diet-induced obese and insulin resistant NAFLD/NASH mouse models were utilized. In addition, tissue specific TSP1 knockout mice were utilized to determine the contribution of different cellular sources of obesity-induced TSP1 to NAFLD/NASH development. The data demonstrated that liver TSP1 levels were increased in experimental obese and insulin resistant NAFLD/NASH mouse models as well as in human obese NASH patients. Moreover, TSP1 deletion in hepatocyte or adipocytes did not protect mice from diet-induced NAFLD/NASH. However, myeloid/macrophage-specific TSP1 deletion protected mice against obesity-associated liver injury, accompanied by reduced liver inflammation and fibrosis. Importantly, this protection is independent of the levels of obesity and hepatic steatosis. Mechanistically, through an autocrine effect, macrophage-derived TSP1 suppressed SMPDL3B expression in liver, which amplified liver pro-inflammatory signaling (TLR4 signal pathway) and promoted NAFLD progression. Together, out data suggest that macrophage-derived TSP1 is a significant contributor to obesity-associated NAFLD/NASH development and progression and may serve as a therapeutic target for this disease.
Overall design TSP1 floxed mice and macrophage specific TSP1 knockout mice were fed with LF or HF diet for 8 months. Then mie were sacrficed and livers were harvested for further analysis.
Contributor(s) Gawg T, Mooli RG, Li D, Lee EY, Wang S
Citation(s) 33294831
Submission date Aug 10, 2020
Last update date Dec 15, 2020
Contact name Shuxia Wang
Phone 8592181367
Organization name University of Kentucky
Department Pharmacology and Nutritional Sciences
Street address 900 S. Limestone street, Wethington Bldg. Room 583
City lexington
State/province KY
ZIP/Postal code 40536
Country USA
Platforms (1)
GPL23479 BGISEQ-500 (Mus musculus)
Samples (12)
GSM4718405 LF TSP1flox-1
GSM4718406 LF TSP1flox-2
GSM4718407 LF TSP1flox-3
BioProject PRJNA656249
SRA SRP276889

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Supplementary file Size Download File type/resource
GSE155973_RAW.tar 28.3 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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