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| Status |
Public on Apr 04, 2019 |
| Title |
Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Metabolism in mammals is regulated by the complex interplay among different organs. Fatty acid synthesis is increased in white adipose tissue (WAT) when it is inhibited in liver. Here we identify glycoprotein nonmetastatic melanoma protein B (Gpnmb) as one liver-WAT cross-talk factor in lipogenesis. Hepatic SREBP pathway inhibition leads to increased transcription of the Gpnmb and promotes the processing of the membrane protein to a secreted form. Gpnmb stimulates lipogenesis in WAT and exacerbates diet-induced obesity and insulin resistance. In humans, Gpnmb is tightly associated with body mass index and is a strong risk factor for obesity. Gpnmb inhibition by a neutralizing antibody or liver specific knockdown improves metabolic parameters including weight gain reduction and increased insulin sensitivity, likely by promoting the beiging of WAT. These results suggest that Gpnmb is a liver-secreted factor regulating lipogenesis in WAT, and that Gpnmb inhibition may provide a therapeutic strategy for obesity and diabetes.
Hepatic SREBP pathway inhibition, such as liver-specific ablation of Scap (L-Scap-/-), decreases fatty acid synthesis in liver. Meanwhile, the fatty acid synthesis in white adipose tissue of L-Scap-/- is compensatorily increased. The microarray analysis using the liver RNAs of L-Scap-/- and wild type (WT) mice is performed to identify the up-regulated genes encoding secreted factors in L-Scap-/-.
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| Overall design |
Total liver RNAs isolated from 8-week-old L-Scap-/- mice and WT littermates (n = 2 mice per group) subjected to microarray analysis
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| Contributor(s) |
Song B, Zhou Z |
| Citation missing |
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| |
| Submission date |
Apr 03, 2019 |
| Last update date |
Apr 05, 2019 |
| Contact name |
Song Bao-Liang |
| E-mail(s) |
blsong@whu.edu.cn
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| Organization name |
Wuhan university
|
| Street address |
College of Life Sciences
|
| City |
Wuhan, Hubei Province |
| ZIP/Postal code |
430072 |
| Country |
China |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| Samples (4)
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| GSM3703956 |
scap K0_1@251486836166_S01_GE1_107_Sep09_1_3 |
| GSM3703957 |
scap K0_2@251486836166_S01_GE1_107_Sep09_1_4 |
| GSM3703958 |
scap WT_1@251486836166_S01_GE1_107_Sep09_1_1 |
| GSM3703959 |
scap WT_2@251486836166_S01_GE1_107_Sep09_1_2 |
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| Relations |
| BioProject |
PRJNA530742 |
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