Peroxiredoxin 6 Is a Key Antioxidant Enzyme in Modulating the Link between Glycemic and Lipogenic Metabolism

Autor: Aikaterini Andreadi, Davide Lauro, Roberto Arriga, Giuseppe Sconocchia, David Della-Morte, Donatella Pastore, Manfredi Tesauro, Nicola Di Daniele, Barbara Capuani, Maria Giovanna Scioli, Andrea Coppola, Augusto Orlandi, Alfonso Bellia, Francesca Pacifici, Paolo Sbraccia, Giulia Donadel
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Blood Glucose
Male
Aging
medicine.medical_treatment
Adipose tissue
Settore MED/08
Settore MED/09
Settore MED/04
Biochemistry
Antioxidants
Mice
0302 clinical medicine
Settore MED/13
Non-alcoholic Fatty Liver Disease
Insulin-Secreting Cells
Medicine
Insulin
2. Zero hunger
Mice
Knockout
Adipogenesis
lcsh:Cytology
General Medicine
3. Good health
Female
Research Article
medicine.medical_specialty
Article Subject
Carbohydrate metabolism
Diet
High-Fat
03 medical and health sciences
Insulin resistance
Downregulation and upregulation
Internal medicine
Lipolysis
Animals
Obesity
lcsh:QH573-671
business.industry
Lipid metabolism
Cell Biology
Metabolism
medicine.disease
Lipid Metabolism
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
Insulin Resistance
business
030217 neurology & neurosurgery
Peroxiredoxin VI
Zdroj: Oxidative Medicine and Cellular Longevity
Oxidative Medicine and Cellular Longevity, Vol 2019 (2019)
ISSN: 1942-0994
1942-0900
Popis: Insulin action and often glucose-stimulated insulin secretion are reduced in obesity. In addition, the excessive intake of lipids increases oxidative stress leading to overt type 2 diabetes mellitus (T2DM). Among the antioxidative defense systems, peroxiredoxin 6 (PRDX6) is able to reduce H2O2 and short chain and phospholipid hydroperoxides. Increasing evidences suggest that PRDX6 is involved in the pathogenesis of atherosclerosis and T2DM, but its role in the etiopathology of obesity and its complications is still not known. Therefore, in the present study, we sought to investigate this association by using PRDX6 knockout mice (PRDX6-/-). Metabolic parameters, like carbon dioxide (VCO2) production, oxygen consumption (VO2), and the respiratory exchange ratio (RER), were determined using metabolic cages. Intraperitoneal insulin and glucose tolerance tests were performed to evaluate insulin sensitivity and glucose tolerance, respectively. Liver and pancreas histochemical analyses were also evaluated. The expression of enzymes involved in lipid and glucose metabolism was analyzed by real-time PCR. Following 24 weeks of high-fat-diet (HFD), PRDX6-/- mice showed weight gain and higher food and drink intake compared to controls. VO2 consumption and VCO2 production decreased in PRDX6-/- mice, while the RER was lower than 0.7 indicating a prevalent lipid metabolism. PRDX6-/- mice fed with HFD showed a further deterioration on insulin sensitivity and glucose-stimulated insulin secretion. Furthermore, in PRDX6-/- mice, insulin did not suppress adipose tissue lipolysis with consequent hepatic lipid overload and higher serum levels of ALT, cholesterol, and triglycerides. Interestingly, in PRDX6-/- mice, liver and adipose tissue were associated with proinflammatory gene upregulation. Finally, PRDX6-/- mice showed a higher rate of nonalcoholic steatohepatitis (NASH) compared to control. Our results suggest that PRDX6 may have a functional and protective role in the development of obesity-related metabolic disorders such as liver diseases and T2DM and may be considered a potential therapeutic target against these illnesses.
Databáze: OpenAIRE
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