The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting
| Autor: | Manali Dimri, Ande Satyanarayana, Sawsan Elattar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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