Forbes-Hernandez 2017 MiPschool Obergurgl
Event: MiPschool Obergurgl 2017
Usually, loss of mitochondrial function- characterized by a reduction of the efficiency in the electron transport chain and reductions in the ATP synthesis- has been linked to the pathogenesis of numerous diseases and their complications. However, it has been recently suggested that perturbation of energy homeostasis in the liver resulting from a temporary inhibition of mitochondrial energy transduction, may actually be relevant in the control of hyperglycemia by activation of the AMP-activated protein kinase (AMPK), [1,2] as illustrated by the antidiabetic drug metformin [1,3,4]. Hence, mitochondrial modulation has been proposed as a prospective therapy for metabolic diseases. Scientific evidence indicates the role of strawberries in the reduction of oxidative damage, the normalization of blood glucose levels, and the improvement of lipid profile. Our group newly demonstrated that diminution of lipid accumulation by strawberry extract depends on the AMPK activation. Since AMPK is activated not only through its upstream kinases but also by an increase in the AMP/ATP ratio, the objective of the present work was to evalute the effect of a strawberry extract on mitochondrial functionality in HepG2 cells.
For that purpose the oxygen consumption rate (OCR) was examined using an XF24 Extracellular Flux Analyzer (Seahorse Bioscience, Billerica MA, USA) and the different respiration rates were calculated.
Increasing concentrations of strawberry extract had no significant (p<0.05) effect on basal respiration while they caused a dose-depending diminution in the spare, the maximal respiration and the ATP turnover compared to the control. Moreover, it significantly (p<0.05) increased the proton leak when it was applied at the higher concentration (100 μg/mL). Therefore, it can be hypothesized that strawberry extract could activate AMPK through alterations on the electron transport chain functionality, subsequently affecting cell energy state. However further analyses should be performed to confirm that the AMP/ATP ratio certainly increases. In addition, strawberry extract decreased intracellular reactive oxygen species (ROS) content and upregulated the expression of the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), which is implicated in mitochondrial biogenesis.
• Bioblast editor: Kandolf G
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Pharmacology;toxicology
Organism: Human Tissue;cell: Liver
Event: D2, Poster Metformin
- Forbes-Hernández TY(1,2), Gasparrini M(2), Afrin S(2), Reboredo P(3), Cianciosi D(2), Varela-López A(4), Giampieri F, Battino M(2,5)
- Área Nutrición Salud, Univ Internacional Iberoamericana (UNINI), Campeche, México
- Dept DISCO, Sez. Biochimica, Fac Medicina, UNIVPM, Ancona, Italy
- Dept Analytical Food Chem, Univ Vigo, Ourense, Spa
- Dept Physiol, Inst Nutrition Food Technol “José Mataix”, Biomedical Research Centre, Univ Granada, Spain
- Centre Nutrition Health, Univ Europea Atlantico (UEA), Santander, Spain.- [email protected]
Figure 1. Effects of strawberry methanolic extract on mitochondrial respiration in HepG2 cells. Cells were treated with the indicated concentration for 24 h. Values are expressed as mean ± SD of three independent experiments (n = 3). Different superscript letters between different strawberry dried methanolic extract concentrations for each parameter in the chart bar indicate statistical significance (p<0.05).
Figure 2. Effects of strawberry methanolic extract on intracellular reactive oxygen species (ROS) production in HepG2 cells. Cells were treated with the indicated concentration of strawberry extracts for 24 h. Scale bar, 50 µm. Representative images of intracellular ROS quantification by the Tali® Image-Based Cytometer (Thermo Fisher Scientific, Milan, Italy) are shown following the graphs (stressed cells appear red). Values are expressed as the mean ± SD of three independent experiments (n = 3). Columns belonging to the same set of data with different superscript letters are significantly different (p < 0.05).
- Martineau LC (2012) Large enhancement of skeletal muscle cell glucose uptake and suppression of hepatocyte glucose-6-phosphatase activity by weak uncouplers of oxidative phosphorylation. Biochim Biophys Acta 1820:133–50.
- Zhang Y, Ye J (2012) Mitochondrial inhibitor as a new class of insulin sensitizer. Acta Pharm Sin B 2:341-9.
- Desler C, Hansen TL, Frederiksen JB, Marcker ML, Singh KK, Rasmussen LJ (2012) Is there a link between mitochondrial reserve respiratory capacity and aging? J Aging Res 192503.
- Owen MR, Doran E, Halestrap AP (2000) Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 348:607-14.