title: Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer.
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.
authors.affiliation: Simone Polvani, Sara Tempesti, Mirko Tarocchi, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50139 Firenze, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Polvani
authors.affiliation: Simone Polvani, Sara Tempesti, Mirko Tarocchi, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50139 Firenze, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Tarocchi
authors.affiliation: Simone Polvani, Sara Tempesti, Mirko Tarocchi, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50139 Firenze, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tempesti
authors.affiliation: Simone Polvani, Sara Tempesti, Mirko Tarocchi, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50139 Firenze, Italy.
authors.forename: Lapo
authors.initials: L
authors.lastname: Bencini
authors.affiliation: Simone Polvani, Sara Tempesti, Mirko Tarocchi, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50139 Firenze, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Galli
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D047495:PPAR gamma
keywords: Adiponectin; Adipose tissue; Inflammation; Insulin; Leptin; Metformin; Nuclear receptor; Pancreatic cancer; Thiazolidinediones