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Impairment of PGC-1 Alpha Up-Regulation Enhances Nitrosative Stress in the Liver during Acute Pancreatitis in Obese Mice
- Source :
- Antioxidants, Antioxidants, Vol 9, Iss 887, p 887 (2020), Biblos-e Archivo. Repositorio Institucional de la UAM, instname, Volume 9, Issue 9, Biblos-e Archivo: Repositorio Institucional de la UAM, Universidad Autónoma de Madrid, Antioxidants (Basel, Switzerland), r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
- Publication Year :
- 2020
-
Abstract
- Acute pancreatitis is an inflammatory process of the pancreatic tissue that often leads to distant organ dysfunction. Although liver injury is uncommon in acute pancreatitis, obesity is a risk factor for the development of hepatic complications. The aim of this work was to evaluate the role of PGC-1&alpha<br />in inflammatory response regulation in the liver and its contribution to the detrimental effect of obesity on the liver during acute pancreatitis. For this purpose, we induced acute pancreatitis by cerulein in not only wild-type (WT) and PGC-1&alpha<br />knockout (KO) mice, but also in lean and obese mice. PGC-1&alpha<br />levels were up-regulated in the mice livers with pancreatitis. The increased PGC-1&alpha<br />levels were bound to p65 to restrain its transcriptional activity toward Nos2. Lack of PGC-1&alpha<br />favored the assembly of the p65/phospho-STAT3 complex, which promoted Nos2 expression during acute pancreatitis. The increased transcript Nos2 levels and the pro-oxidant liver status caused by the down-regulated expression of the PGC-1&alpha<br />dependent antioxidant genes enhanced nitrosative stress and decreased energy charge in the livers of the PGC-1&alpha<br />KO mice with pancreatitis. It is noteworthy that the PGC-1&alpha<br />levels lowered in the obese mice livers, which increased the Nos2 mRNA expression and protein nitration levels and decreased energy charge during pancreatitis. In conclusion, obesity impairs PGC-1&alpha<br />up-regulation in the liver to cause nitrosative stress during acute pancreatitis.
- Subjects :
- PGC-1α
0301 basic medicine
obesity
medicine.medical_specialty
Antioxidant
acute pancreatitis
Physiology
medicine.medical_treatment
Clinical Biochemistry
PGC-1α
Alpha (ethology)
Nitrosative stress
liver
Hepatic Complication
Biochemistry
Article
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Internal medicine
medicine
Obesity
Molecular Biology
Liver injury
business.industry
lcsh:RM1-950
Organ dysfunction
Cell Biology
Biología y Biomedicina / Biología
medicine.disease
nitrosative stress
Acute pancreatitis
lcsh:Therapeutics. Pharmacology
030104 developmental biology
Endocrinology
Liver
030220 oncology & carcinogenesis
Pancreatitis
medicine.symptom
business
Subjects
Details
- ISSN :
- 20763921
- Database :
- OpenAIRE
- Journal :
- Antioxidants
- Accession number :
- edsair.doi.dedup.....5d1b6065715fdf3df741c96517ec9152
- Full Text :
- https://doi.org/10.3390/antiox9090887