Glucagon-like peptide-1 receptor agonist stimulates mitochondrial bioenergetics in human adipocytes

• Authors: Joanna Góralska , Agnieszka Śliwa , Anna Gruca , Urszula Raźny , Monika Chojnacka , Anna Polus , Bogdan Solnica , Małgorzata Malczewska-Malec
• Languages of publication: EN

Abstracts

EN

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions. For this purpose, preadipocytes CHUBS7 were differentiated to mature adipocytes and then stimulated with GLP-1RA, exendin-4 at 100 nM for 24 h. Oxygen consumption rates, mitochondrial membrane potential, intracellular ATP (adenosine triphosphate) level, SIRT1 and SIRT3 gene expression and the histone deacetylases' activity were measured. Exendin-4 was found to uncouple mitochondrial electron transport from ATP synthesis, slightly decreasing mitochondrial membrane potential in mature adipocytes. Routine respiration and uncoupled oxy- gen consumption rates were higher in exendin-4 treated adipocytes than in the non-treated cells. The ATP level remained unchanged. Exendin-4 enhanced SIRT1 and SIRT3 genes expression. Histone deacetylases' activity in the nuclear fraction was not affected by exendin-4, although the activity of class III histone deacetylases was increased. All of the effects on mitochondrial bioenergetics induced by exendin-4 were abolished by addition of glucagon-like peptide 1 receptor antagonist. In conclusion, exendin-4 activates the sirtuin pathway and increases energy expenditure in human adipocytes. Our results suggest another mechanism that may be responsible for body weight reduction observed in patients using GLP-1RAs.

Keywords

EN

exendin-4; GLP-1; mitochondria; sirtuin; mitochondrial respiration

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2017
• Volume: 64
• Issue: 3
• Pages: 423-429

Dates

published

2017

received

2017-03-19

revised

2017-06-25

accepted

2017-06-29

(unknown)

2017-08-19

Contributors

author

Joanna Góralska

• Department of Clinical Biochemistry, Medical College, Jagiellonian University, Kraków, Poland

author

Agnieszka Śliwa

• Department of Clinical Biochemistry, Medical College, Jagiellonian University, Kraków, Poland

author

Anna Gruca

• Department of Clinical Biochemistry, Medical College, Jagiellonian University, Kraków, Poland

author

Urszula Raźny

• Department of Clinical Biochemistry, Medical College, Jagiellonian University, Kraków, Poland

author

Monika Chojnacka

• Department of Clinical Biochemistry, Medical College, Jagiellonian University, Kraków, Poland

author

Anna Polus

• Department of Clinical Biochemistry, Medical College, Jagiellonian University, Kraków, Poland

author

Bogdan Solnica

• Department of Clinical Biochemistry, Medical College, Jagiellonian University, Kraków, Poland

author

Małgorzata Malczewska-Malec

• Department of Clinical Biochemistry, Medical College, Jagiellonian University, Kraków, Poland

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Identifiers

DOI

10.18388/abp.2017_1634