Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Tumor Suppressor Par-4 Regulates Complement Factor C3 and Obesity

Araujo, Nathalia ; Sledziona, James ; Noothi, Sunil K. ; Burikhanov, Ravshan ; Hebbar, Nikhil ; Ganguly, Saptadwipa ; Shrestha-Bhattarai, Tripti ; Zhu, Beibei ; Katz, Wendy S. and Zhang, Yi , et al. (2022) In Frontiers in Oncology 12.
Abstract

Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed the obese mouse phenotype. Moreover,... (More)

Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed the obese mouse phenotype. Moreover, obese human subjects showed lower expression of Par-4 relative to lean subjects, and in longitudinal studies, low baseline Par-4 levels denoted an increased risk of developing obesity later in life. These findings indicate that Par-4 suppresses p53 and its target c3 to regulate obesity.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
acylation stimulating protein, adipocyte tissue storage, C3, fat absorption, hypertrophic obesity, Par-4
in
Frontiers in Oncology
volume
12
article number
860446
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85128400591
  • pmid:35425699
ISSN
2234-943X
DOI
10.3389/fonc.2022.860446
language
English
LU publication?
yes
id
cda31091-556c-4107-8f7f-1b5bc2d2f324
date added to LUP
2022-07-06 14:51:34
date last changed
2024-06-13 09:58:09
@article{cda31091-556c-4107-8f7f-1b5bc2d2f324,
  abstract     = {{<p>Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4<sup>-/-</sup>) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4<sup>-/-</sup> and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed the obese mouse phenotype. Moreover, obese human subjects showed lower expression of Par-4 relative to lean subjects, and in longitudinal studies, low baseline Par-4 levels denoted an increased risk of developing obesity later in life. These findings indicate that Par-4 suppresses p53 and its target c3 to regulate obesity.</p>}},
  author       = {{Araujo, Nathalia and Sledziona, James and Noothi, Sunil K. and Burikhanov, Ravshan and Hebbar, Nikhil and Ganguly, Saptadwipa and Shrestha-Bhattarai, Tripti and Zhu, Beibei and Katz, Wendy S. and Zhang, Yi and Taylor, Barry S. and Liu, Jinze and Chen, Li and Weiss, Heidi L. and He, Daheng and Wang, Chi and Morris, Andrew J. and Cassis, Lisa A. and Nikolova-Karakashian, Mariana and Nagareddy, Prabhakar R. and Melander, Olle and Evers, B. Mark and Kern, Philip A. and Rangnekar, Vivek M.}},
  issn         = {{2234-943X}},
  keywords     = {{acylation stimulating protein; adipocyte tissue storage; C3; fat absorption; hypertrophic obesity; Par-4}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Oncology}},
  title        = {{Tumor Suppressor Par-4 Regulates Complement Factor C3 and Obesity}},
  url          = {{http://dx.doi.org/10.3389/fonc.2022.860446}},
  doi          = {{10.3389/fonc.2022.860446}},
  volume       = {{12}},
  year         = {{2022}},
}