Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence

Abstract

Fatty acid b-oxidation (FAO) is essential for oocyte maturation in mice. The objective of this study was to determine the effect of etomoxir (a FAO inhibitor; 100 mM), carnitine (1 mM), and palmitic acid (1 or 100 mM) during maturation on metabolism and gene expression of the oocyte and cumulus cells, and subsequent embryo development in the mouse. Carnitine significantly increased embryo development, while there was a decrease in development following maturation with 100 mM palmitic acid or etomoxir (P!0.05) treatment. Glucose consumption per cumulus-oocyte complex (COC) was decreased after treatment with carnitine and increased following etomoxir treatment (P!0.05). Intracellular oocyte lipid content was decreased after carnitine or etomoxir exposure (P!0.05). Abundance of Slc2a1 (Glut1) was increased after etomoxir treatment in the oocyte and cumulus cells (P!0.05), suggesting stimulation of glucose transport and potentially the glycolytic pathway for energy production when FAO is inhibited. Abundance of carnitine palmitoyltransferase 2 (Cpt2) tended to increase in oocytes (PZ0.1) after treatment with 100 mM palmitic acid and in cumulus cells after exposure to 1 mM palmitic acid (PZ0.07). Combined with carnitine, 1 mM palmitic acid increased the abundance of Acsl3 (P!0.05) and Cpt2 tended to increase (PZ0.07) in cumulus cells, suggesting FAO was increased during maturation in response to stimulators and fatty acids. In conclusion, fatty acid and glucose metabolism are related to the mouse COC, as inhibition of FAO increases glucose consumption. Stimulation of FAO decreases glucose consumption and lipid stores, positively affecting subsequent embryo development, while an overabundance of fatty acid or reduced FAO negatively affects oocyte quality.

The role of l-carnitine during oocyte in vitro maturation: essential co-factor?

“…These studies demonstrate a requirement for beta-oxidation in nuclear maturation (Downs et al, 2009;Valsangkar and Downs, 2013;Paczkowski et al, 2014;Sanchez-Lazo et al, 2014), as described above, and in the acquisition of oocyte developmental competence in mouse, bovine and porcine oocytes (Ferguson and Leese, 2006;Sturmey et al, 2006;Dunning et al, 2010;Paczkowski et al, 2014).…”

“…The beneficial effects of L-carnitine supplementation on oocyte quality can at least be partially ascribed to its effects on stimulating fatty acid beta-oxidation. The role of supplying exogenous fatty acid to IVM for utilization via betaoxidation, at least in the mouse, appears detrimental (Paczkowski et al, 2014). This may be due to the concentration or type of fatty acid used in this study.…”

“…There is a growing number of studies that have investigated the role of L-carnitine during IVM in various species including mouse (Dunning et al, 2010(Dunning et al, , 2011Paczkowski et al, 2014), bovine (Ferguson and Leese, 2006;Phongnimitr et al, 2013;Giorgi et al, 2016;Sovernigo et al, 2017), porcine (Hashimoto, 2009;Somfai et al, 2011;Wu et al, 2011;You et al, 2012) and sheep (Reader et al, 2015;Mishra et al, 2016a). The effects of L-carnitine on oocyte quality and the associated mechanism(s) are detailed in the following sections.…”

“…There is a growing body of literature describing the importance of fatty acid beta-oxidation as a source of energy during oocyte IVM (Ferguson and Leese, 2006;Sturmey et al, 2006;Downs et al, 2009;Dunning et al, 2010;Dunning and Robker, 2012;Valsangkar and Downs, 2013;Dunning et al, 2014b;Paczkowski et al, 2014). This is not surprising when one considers the energy dense nature of fatty acids with the potential to produce 106 ATP molecules from a single fatty acid, greater than 3.5-fold the capacity of a single glucose molecule.…”

“…Beta-oxidation appears to be important for oocyte nuclear maturation; meiotic maturation to metaphase II and extrusion of the first polar body (Downs et al, 2009;Valsangkar and Downs, 2013;Paczkowski et al, 2014). Further, it appears that betaoxidation is important in the acquisition of oocyte developmental competence (reviewed in McKeegan and Sturmey, 2011;Dunning et al, 2014b).…”