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

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Góralska J., Śliwa A., Gruca A., Raźny U., Chojnacka M., Polus A., Solnica B., Malczewska-Malec M.

Acta Biochimica Polonica

2017

vol. 64

issue 3

423-429

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.

Relation of the protein glycation, oxidation and nitration to the osteocalcin level in obese subjects

81%

Razny U., Goralska J., Zdzienicka A., Fedak D., Masania J., Rabbani N., Thornalley P., Pawlica-Gosiewska D., Gawlik K., Dembinska-Kiec A., Solnica B., Malczewska-Malec M.

Acta Biochimica Polonica

2017

vol. 64

issue 3

415-422

Carboxylated osteocalcin (Gla-OC) contributes to the bone formation, whereas its undercarboxylated form (Glu-OC) takes part in the energy metabolism. In vitro studies had shown that treatment of osteoblast-like cells with advanced glycation end product-modified bovine serum resulted in reduced synthesis of collagen 1 and osteocalcin. The aim of this study was to find association between Gla-OC and markers of protein glycation, oxidation and nitration, as well as pro-inflammatory and antioxidant defense markers in obese subjects. Non-obese [(body mass index (BMI)<30 kg/m; n=34)] and obese subjects (30

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2 Acta Biochimica Polonica

2 2017

2 Malczewska-Malec M.

2 Solnica B.

1 Chojnacka M.

1 Dembinska-Kiec A.

1 Fedak D.

1 Gawlik K.

1 Goralska J.

1 Gruca A.

1 Góralska J.

1 Masania J.

1 Pawlica-Gosiewska D.

1 Polus A.

1 Rabbani N.

1 Razny U.

1 Raźny U.

1 Thornalley P.

1 Zdzienicka A.

1 Śliwa A.

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

Relation of the protein glycation, oxidation and nitration to the osteocalcin level in obese subjects