The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting

Sawsan Elattar, Manali Dimri, Satyanarayana Ande

Research output: Contribution to journalArticle

7 Citations (Scopus)

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-a 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 g (PPARg) 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 PPARg and PPARg coactivator 1a and promoted recruitment of PPARg 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.

Original languageEnglish (US)
Pages (from-to)4727-4743
Number of pages17
JournalFASEB Journal
Volume32
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

White Adipose Tissue
Zinc
Tumors
Glycoproteins
Tissue
Peroxisomes
Neoplasms
Cachexia
Wasting Syndrome
Brown Adipose Tissue
Lipolysis
Anorexia
Fibroblasts
Recombinant Proteins
Energy Metabolism
Adipose Tissue
Proteins
B-Lymphocytes
Cells
Inflammation

Keywords

  • Beige adipocyte
  • Cachexia
  • Ebf2
  • Prdm16
  • Ucp1

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting. / Elattar, Sawsan; Dimri, Manali; Ande, Satyanarayana.

In: FASEB Journal, Vol. 32, No. 9, 01.09.2018, p. 4727-4743.

Research output: Contribution to journalArticle

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