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Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance
- Source :
- Nature Metabolism. 1:570-583
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Metabolism in mammals is regulated by complex interplay among different organs. Fatty acid synthesis is increased in white adipose tissue (WAT) when it is inhibited in the liver. Here we identify glycoprotein non-metastatic melanoma protein B (Gpnmb) as one liver-WAT cross-talk factor involved in lipogenesis. Inhibition of the hepatic sterol regulatory element-binding protein pathway leads to increased transcription of Gpnmb and promotes 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, probably 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 in obesity and diabetes.
- Subjects :
- medicine.medical_specialty
Adipose Tissue, White
Endocrinology, Diabetes and Metabolism
Adipose tissue
White adipose tissue
Mice
chemistry.chemical_compound
Insulin resistance
Downregulation and upregulation
Physiology (medical)
Internal medicine
Internal Medicine
medicine
Animals
Homeostasis
Obesity
Eye Proteins
Fatty acid synthesis
Mice, Knockout
Membrane Glycoproteins
GPNMB
Lipogenesis
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Lipid metabolism
Cell Biology
Lipid Metabolism
medicine.disease
Up-Regulation
Receptors, Autocrine Motility Factor
Endocrinology
Liver
chemistry
Insulin Resistance
Subjects
Details
- ISSN :
- 25225812
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Metabolism
- Accession number :
- edsair.doi.dedup.....75b7c049a134da5e1d598768abee382a