Optimal HSF1 activation in response to acute cold stress in BAT requires nuclear TXNIP

Althea N Waldhart; Kin H Lau; Holly Dykstra; Tracey Avequin; Ning Wu

doi:10.1016/j.isci.2023.106538

Optimal HSF1 activation in response to acute cold stress in BAT requires nuclear TXNIP

iScience. 2023 Apr 10;26(5):106538. doi: 10.1016/j.isci.2023.106538. eCollection 2023 May 19.

Authors

Althea N Waldhart¹, Kin H Lau¹, Holly Dykstra¹, Tracey Avequin¹, Ning Wu¹

Affiliation

¹ Van Andel Institute, Grand Rapids, MI 49503, USA.

Abstract

While TXNIP (thioredoxin interacting protein) in the plasma membrane and vesicular location is known to negatively regulate cellular glucose uptake by facilitating glucose transporter endocytosis, the function of TXNIP in the nucleus is far less understood. Herein, we sought to determine the function of nuclear TXNIP in vivo, using a new HA-tagged TXNIP knock-in mouse model. We observed that TXNIP can be found in the nucleus of a variety of cells from different tissues including hepatocytes (liver), enterocytes (small intestine), exocrine cells (pancreas), and brown adipocytes (BAT). Further investigations into the role of nuclear TXNIP in BAT revealed that cold stress rapidly and transiently activated HSF1 (heat shock factor 1). HSF1 interaction with TXNIP during its activation is required for optimal HSF1 directed cold shock response in BAT.

Keywords: Biological sciences; Molecular biology; Molecular interaction; Physiology.

Grants and funding

R01 GM120129/GM/NIGMS NIH HHS/United States