Glucose Increases Hepatic Mitochondrial Antioxidant Enzyme Activities in Insulin Resistant Rats Following Chronic Angiotensin Receptor Blockade

Autor: Jose A. Godoy-Lugo, Max A. Thorwald, Dora A. Mendez, Ruben Rodriguez, Daisuke Nakano, Akira Nishiyama, Rudy M. Ortiz
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Male
collagen
Interleukin-1beta
Angiotensin-Converting Enzyme Inhibitors
Antioxidants
Angiotensin
Non-alcoholic Fatty Liver Disease
Receptors
Insulin
2.1 Biological and endogenous factors
Aetiology
Spectroscopy
Receptors
Angiotensin
Liver Disease
Diabetes
General Medicine
Catalase
Oxidants
Computer Science Applications
Type 2
Collagen Type IV
NF-E2-Related Factor 2
Glutamate-Cysteine Ligase
Chronic Liver Disease and Cirrhosis
Catalysis
Inorganic Chemistry
Angiotensin Receptor Antagonists
AT1
NAFLD
4-HNE
antioxidants
fibrosis
Diabetes Mellitus
Genetics
Animals
Obesity
Physical and Theoretical Chemistry
Molecular Biology
Metabolic and endocrine
Nutrition
Chemical Physics
Prevention
Organic Chemistry
Rats
Glucose
Diabetes Mellitus
Type 2
Insulin Resistance
Other Biological Sciences
Digestive Diseases
Other Chemical Sciences
Zdroj: International Journal of Molecular Sciences; Volume 23; Issue 18; Pages: 10897
International journal of molecular sciences, vol 23, iss 18
ISSN: 1422-0067
DOI: 10.3390/ijms231810897
Popis: Non-alcoholic fatty liver disease (NAFLD) affects up to 20% of the world’s population. Overactivation of the angiotensin receptor type 1 (AT1) contributes to metabolic dysfunction and increased oxidant production, which are associated with NAFLD and impaired hepatic lipid metabolism. Nuclear factor erythroid-2-related factor 2 (Nrf2) regulates the expression of antioxidant phase II genes by binding to the antioxidant response element (ARE); however, the mechanisms by which AT1 contributes to this pathway during the progression of NAFLD remain unresolved. To investigate hepatic Nrf2 response to a hyperglycemic challenge, we studied three groups of rats (male, 10-weeks-old): (1) untreated, lean Long Evans Tokushima Otsuka (LETO), (2) untreated, obese Otsuka Long Evans Tokushima Fatty (OLETF), and (3) OLETF + angiotensin receptor blocker (OLETF + ARB; 10 mg olmesartan/kg/d × 6 weeks). Livers were collected after overnight fasting (T0; baseline), and 1 h and 2 h post-oral glucose load. At baseline, chronic AT1 blockade increased nuclear Nrf2 content, reduced expression of glutamate-cysteine ligase catalytic (GCLC) subunit, glutathione peroxidase 1 (GPx1), and superoxide dismutase 2 (SOD2), mitochondrial catalase activity, and hepatic 4-hydroxy-2-nonenal (4-HNE) content. The expression of hepatic interleukin-1 beta (IL-1β) and collagen type IV, which are associated with liver fibrosis, were decreased with AT1 blockade. Glucose increased Nrf2 translocation in OLETF but was reduced in ARB, suggesting that glucose induces the need for antioxidant defense that is ameliorated with ARB. These results suggest that overactivation of AT1 promotes oxidant damage by suppressing Nrf2 and contributing to hepatic fibrosis associated with NAFLD development.
Databáze: OpenAIRE
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