Obesity causes PGC-1α deficiency in the pancreas leading to marked IL-6 upregulation via NF-κB in acute pancreatitis

The Journal of Pathology
Salvador PérezJuan Sastre

Abstract

Obesity is associated with local and systemic complications in acute pancreatitis. PPARγ coactivator 1α (PGC-1α) is a transcriptional coactivator and master regulator of mitochondrial biogenesis that exhibits dysregulation in obese subjects. Our aims were: (1) to study PGC-1α levels in pancreas from lean or obese rats and mice with acute pancreatitis; and (2) to determine the role of PGC-1α in the inflammatory response during acute pancreatitis elucidating the signaling pathways regulated by PGC-1α. Lean and obese Zucker rats and lean and obese C57BL6 mice were used first; subsequently, wild-type and PGC-1α knockout (KO) mice with cerulein-induced pancreatitis were used to assess the inflammatory response and expression of target genes. Ppargc1a mRNA and protein levels were markedly downregulated in pancreas of obese rats and mice versus lean animals. PGC-1α protein levels increased in pancreas of lean mice with acute pancreatitis, but not in obese mice with pancreatitis. Interleukin-6 (Il6) mRNA levels were dramatically upregulated in pancreas of PGC-1α KO mice after cerulein-induced pancreatitis in comparison with wild-type mice with pancreatitis. Edema and the inflammatory infiltrate were more intense in pancreas from PGC-1α...Continue Reading

References

Jan 1, 1992·The Journal of Clinical Investigation·B A Neuschwander-TetriJ H Grendell
Dec 9, 1998·The American Journal of Physiology·I GukovskyS J Pandol
Jan 29, 1999·Gastroenterology·A U SteinleR M Schmid
Jul 27, 2000·American Journal of Physiology. Endocrinology and Metabolism·X X YuS H Adams
Feb 8, 2002·Gastroenterology·Xueqing ChenCraig D Logsdon
Jan 1, 2004·American Journal of Physiology. Endocrinology and Metabolism·Kenneth FeingoldCarl Grunfeld
May 6, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Simon A JonesStefan Rose-John
Mar 22, 2006·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·J MartínezM Pérez-Mateo
Apr 26, 2006·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Georgios I PapachristouDavid C Whitcomb
Jan 4, 2007·The Journal of Clinical Investigation·Carey N LumengAlan R Saltiel
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takahito HayashiToshikazu Kondo
May 26, 2007·The Journal of Clinical Investigation·Bernd BaumannThomas Wirth
Feb 19, 2008·Free Radical Biology & Medicine·Javier PeredaJuan Sastre
May 24, 2008·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Laura SempereMiguel Perez-Mateo
Jun 3, 2008·Proceedings of the National Academy of Sciences of the United States of America·Joseph A SennelloGiamila Fantuzzi
Jun 28, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Nicholas J ZyromskiDeborah A Swartz-Basile
Mar 10, 2010·Cardiovascular Research·David Alvarez-GuardiaManuel Vázquez-Carrera
Feb 4, 2011·The American Journal of Clinical Nutrition·Pablo J Fernandez-Marcos, Johan Auwerx
Feb 9, 2012·The Journal of Biological Chemistry·Simone ReipschlägerGudula Schmidt
Feb 22, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Anna A BirukovaKonstantin G Birukov
Apr 12, 2012·World Journal of Surgery·D P O'LearyH P Redmond
Feb 22, 2013·The Journal of Clinical Investigation·Hong ZhangHana Algül
Apr 30, 2013·Gastroenterology·Bechien U Wu, Peter A Banks
Nov 22, 2013·Seminars in Immunopathology·Petra S Eisele, Christoph Handschin
Aug 27, 2014·Free Radical Biology & Medicine·Salvador PérezJuan Sastre
May 31, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Soon-Sun HongYongseok Choi
Sep 4, 2015·Gastroenterology·Anne F PeeryRobert S Sandler

❮ Previous
Next ❯

Citations

Apr 16, 2019·The Journal of Pathology·Miguel Fontecha-BarriusoAna B Sanz
Feb 28, 2020·Biomolecules·Miguel Fontecha-BarriusoAna Belen Sanz
Aug 31, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xinzhi LiColin D Funk
Mar 28, 2020·Oxidative Medicine and Cellular Longevity·Sergio Rius-PérezSalvador Pérez

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.