Depletion of ASK1 blunts stress-induced senescence in adipocytes. (1st January 2020)

• Record Type: Journal Article
• Authors: Wueest, Stephan; Lucchini, Fabrizio C.; Haim, Yulia; Rudich, Assaf; Konrad, Daniel
• Is Part Of: Adipocyte. Volume 9:Number 1(2020)
• Page Start: 535
• Page End: 541
• Publication Date: 2020-01-01
• Subjects: Obesity -- diabetes -- browning -- adipose tissue -- subcutaneous -- lipopolysaccharide -- p38 MAPK; Fat cells -- Periodicals; Adipocytes -- Periodicals; 611.018276
• DOI: 10.1080/21623945.2020.1815977
• Languages: English
• ISSNs: 2162-3945

Abstract

ABSTRACT: Increasing energy expenditure via induction of browning in white adipose tissue has emerged as a potential strategy to treat obesity and associated metabolic complications. We previously reported that ASK1 inhibition in adipocytes protected from high-fat diet (HFD) or lipopolysaccharide (LPS)-mediated downregulation of UCP1 both in vitro and in vivo . Conversely, adipocyte-specific ASK1 overexpression attenuated cold-induction of UCP-1 in inguinal fat. Herein, we provide evidence that both TNFα-mediated and HFD-induced activation of p38 MAPK in white adipocytes are ASK1-dependent. Moreover, expression of senescence markers was reduced in HFD-fed adipocyte-specific ASK1 knockout mice. Similarly, LPS-induced upregulation of senescence markers was blunted in ASK1-depleted adipocytes. Thus, our study identifies a previously unknown role for ASK1 in the induction of stress-induced senescence.