Cold exposure reinstates NAD+ levels and attenuates hepatocellular carcinoma
Authors:Tatiana P Grazioso1,2,3, Maria del Mar Rigual1, Cristian Perna4,5, Eduardo J Caleiras6 and Nabil Djouder1
1 Growth Factors, Nutrients and Cancer Group, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, ES28029, Spain. 2 Instituto de Investigación Sanitaria HM Hospitales (IISHM), Madrid, Spain. 3 Laboratory of Innovation in Oncology, Gynecological, Genitourinary and Skin Cancer Unit, HM CIOCC, Centro Integral Oncológico Clara Campal, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, ES-28050, Spain. 4 Department of Pathology, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, ES28034, Spain. 5 Universidad de Alcalá, Madrid, ES28801, Spain. 6 Histopathology Core Unit, Biotechnology Programme, CNIO, Madrid, ES-28029, Spain.
Keywords:
cold exposure, hypthermia, NASH, HCC, NAD+, cell cycle, G2/M.
Abbreviations:
ALT - alanine aminotransferase,
AMPK - AMP-activated protein kinase,
BAT - brown adipose tissue,
CBT - core body temperature,
CT - cold temperature,
HCC - hepatocellular carcinoma,
NASH - non-alcoholic steatohepatitis,
RT - room temperature,
URI - unconventional prefoldin RPB5 interactor,
WAT - white adipose tissue.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Tatiana P Grazioso, Maria del Mar Rigual, Cristian Perna, Eduardo J Caleiras, Nabil Djouder (2024). Cold exposure reinstates NAD+ levels and attenuates hepatocellular carcinoma. Cell Stress 8: 125-139. doi: 10.15698/cst2024.12.302
© 2024 Grazioso et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Cold exposure has been historically used for medicinal purposes, but its benefits and associated mechanisms in mammalian organisms still remain unclear. Here, we explore the chemoprotective properties of cold temperature using a mouse model of hepatocellular carcinoma (HCC) that recapitulates several human features. Chronic cold exposure is shown to prolong lifespan in diseased mice, enhance liver health, and suppress the development of aggressive HCC, preventing hepatocellular hypertrophy, high-grade oval cell hyperplasia, liver steatosis, and aberrant hepatocyte hyperproliferation. Mechanistically, exposure to cold temperatures reinstates NAD+ levels in the HCC mouse models that originally exhibited low NAD+ levels, a contributing process to the development of liver tumors. These findings uncover the role of cold therapy to attenuate HCC development and potentially other existing malignancies involving NAD+ modulation.