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The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting
- Publication Year :
- 2018
- Publisher :
- Federation of American Societies for Experimental Biology, 2018.
-
Abstract
- Cachexia is a complex tissue-wasting syndrome characterized by inflammation, hypermetabolism, increased energy expenditure, and anorexia. Browning of white adipose tissue (WAT) is one of the significant factors that contribute to energy wasting in cachexia. By utilizing a cell implantation model, we demonstrate here that the lipid mobilizing factor zinc-α(2)-glycoprotein (ZAG) induces WAT browning in mice. Increased circulating levels of ZAG not only induced lipolysis in adipose tissues but also caused robust browning in WAT. Stimulating WAT progenitors with ZAG recombinant protein or expression of ZAG in mouse embryonic fibroblasts (MEFs) strongly enhanced brown-like differentiation. At the molecular level, ZAG stimulated peroxisome proliferator–activated receptor γ (PPARγ) and early B cell factor 2 expression and promoted their recruitment to the PR/SET domain 16 (Prdm16) promoter, leading to enhanced expression of Prdm16, which determines brown cell fate. In brown adipose tissue, ZAG stimulated the expression of PPARγ and PPARγ coactivator 1α and promoted recruitment of PPARγ to the uncoupling protein 1 (Ucp1) promoter, leading to increased expression of Ucp1. Overall, our results reveal a novel function of ZAG in WAT browning and highlight the targeting of ZAG as a potential therapeutic application in humans with cachexia.—Elattar, S., Dimri, M., Satyanarayana, A. The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting.
- Subjects :
- 0301 basic medicine
Cachexia
Adipose Tissue, White
Adipose tissue
White adipose tissue
Zn-Alpha-2-Glycoprotein
Biochemistry
03 medical and health sciences
Mice
0302 clinical medicine
Adipose Tissue, Brown
Neoplasms
Brown adipose tissue
Genetics
medicine
Lipolysis
Animals
Molecular Biology
Transcription factor
Uncoupling Protein 1
PRDM16
Chemistry
Research
Seminal Plasma Proteins
Biological Transport
Thermogenesis
Thermogenin
Cell biology
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Energy Metabolism
Biotechnology
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....919ea7c110aff373583432d529e3866e