Depletion of ASK1 blunts stress-induced senescence in adipocytes

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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