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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2016; 22(8): 2441-2459
Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2441
Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer
Simone Polvani, Mirko Tarocchi, Sara Tempesti, Lapo Bencini, Andrea Galli
Simone Polvani, Sara Tempesti, Mirko Tarocchi, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Firenze, Italy
Lapo Bencini, Chirurgia Generale Oncologica, Azienda Ospedaliero Universitaria Careggi, 50139 Firenze, Italy
Author contributions: Polvani S made the literature review and wrote the manuscript; Tempesti S, Tarocchi M and Bencini L critically revised the manuscript; Galli A supervised the manuscript; all authors approved the final version of the manuscript.
Supported by Fondo per gli Investimenti della Ricerca di Base, No. RBAP10MY35_002; Ente Cassa di Risparmio di Firenze, and FiorGen ONLUS to Galli A.
Conflict-of-interest statement: The authors have nothing to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andrea Galli, MD, PhD, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, viale Pieraccini 6, 50139 Firenze, Italy. a.galli@dfc.unifi.it
Telephone: +39-055-2758433 Fax: +39-055-2758433
Received: September 28, 2015
Peer-review started: September 29, 2015
First decision: November 27, 2015
Revised: December 17, 2015
Accepted: January 9, 2016
Article in press: January 11, 2016
Published online: February 28, 2016
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks (sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ (PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stress-associated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients.

Keywords: Insulin, Pancreatic cancer, Adipose tissue, Metformin, Nuclear receptor, Leptin, Adiponectin, Inflammation, Thiazolidinediones

Core tip: Pancreatic cancer has a dismal prognosis with an overall five years survival less than 5%. Obesity and diabetes are risk factors of pancreatic ductal adenocarcinoma (PDAC) increasing the likelihood of its development. Agonists of one specific nuclear receptor transcription factor, the peroxisome proliferator-activated receptor γ (PPARγ), are currently used or evaluated for the treatment of these diseases. PPARγ is a well-known protein implicated in the regulation of metabolism, inflammation, and differentiation; standing at the cross-road of these diseases it may be a key factor linking PDAC to diabetes and obesity, a master regulator whose modulation could be the key for PDAC treatment.