Leptin Modulates Mitochondrial Function, Dynamics and Biogenesis in MCF-7 Cells.
The adipokine leptin, known for its key role in the control of energy metabolism, has been shown to be involved in both normal and tumoral mammary growth. One of the hallmarks of cancer is an alteration of tumor metabolism since cancerous cells must rewire metabolism to satisfy the demands of growth and proliferation. Considering the sensibility of breast cancer cells to leptin, the objective of this study was to explore the effects of this adipokine on their metabolism. To this aim, we treated the MCF-7 breast cancer cell line with 50 ng/mL leptin and analyzed several features related to cellular and mitochondrial metabolism. As a result, leptin increased cell proliferation, shifted ATP production from glycolysis to mitochondria and decreased the levels of the glycolytic end-product lactate. We observed an improvement in ADP-dependent oxygen consumption and an amelioration of oxidative stress without changes in total mitochondrial mass or specific oxidative phosphorylation (OXPHOS) complexes. Furthermore, RT-PCR and western blot showed an up-regulation for genes and proteins related to biogenesis and mitochondrial dynamics. This expression signature, together with an increased mitophagy observed by confocal microscopy suggests that leptin may improve mitochondrial quality and function. Taken together, our results propose that leptin may improve bioenergetic efficiency by avoiding the production of reactive oxygen species (ROS) and conferring benefits for growth and survival of MCF-7 breast cancer cells.
Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Palma de Mallorca, Illes Balears, Spain.|Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain.
M Mar
MM
Blanquer-Rosselló
Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Palma de Mallorca, Illes Balears, Spain.|Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain.
Francisca M
FM
Santandreu
Jordi
J
Oliver
Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Palma de Mallorca, Illes Balears, Spain.|Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain.
Pilar
P
Roca
Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Palma de Mallorca, Illes Balears, Spain.|Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain.
Adamo
A
Valle
D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects; D063306:Mitophagy; D018384:Oxidative Stress / Q000187:drug effects*
D020738:Leptin; D019344:Lactic Acid
BIOENERGETIC; BIOGENESIS; BREAST CANCER; FISSION; FUSION; LEPTIN; MITOCHONDRIA; MITOPHAGY