Needless to say FA must enter

Needless to say, FA must enter into the cell in order to be metabolized. One of the proteins involved in FA uptake is FAT/CD36, an integral membrane glycoprotein which has been found in a wide variety of cells (Abumrad et al., 1993, Coburn et al., 2000, Bonen et al., 2004). Once FA are incorporated into the cells, they are activated by covalently linking to coenzyme A forming an acyl-CoA derivative. Thereafter, the carnitine-palmitoyltransferase 1 (CPT1) is responsible for the entrance of acyl-CoA into the mitochondria where β-oxidation takes place (Rasmussen and Wolfe, 1999). β-oxidation involves the stepwise removal of acetyl-CoA molecules from the shrinking FA chain. The first step is the α-β-dehydrogenation of the acyl-CoA by a family of specific chain length acyl-CoA dehydrogenases (Ghisla and Thorpe, 2004). This family includes, among others, long chain (LCAD) and medium chain (MCAD) dehydrogenases. The molecular events necessary for FA oxidation are strictly controlled and their regulation varies within different tissues (McGarry and Foster, 1980, Lopaschuk et al., 1994, Rasmussen and Wolfe, 1999). Additionally, an association between FA oxidation and regulation of mitochondrial biogenesis in various tissues has been observed (Deepa et al., 2013, O’Neill et al., 2013, Santillo et al., 2013). To this respect, it has been shown that regulation of mitochondrial biogenesis is a crucial mechanism for cellular KB SRC 4 sale in response to hormonal environment and energy deprivation. For instance, induction of mitochondrial biogenesis can be observed in skeletal muscle in response to exercise (Joseph et al., 2006), in brown adipose tissue in adaptative thermogenesis (Butow and Bahassi, 1999) and in white adipose tissue during differentiation (Wilson-Fritch et al., 2003). In Sertoli cells, a cell type that utilizes FA as the main source of energy, it is reasonable to assume that the genes involved in mitochondrial biogenesis and those involved in FA oxidation may be somehow associated and regulated by hormones. It is well known that Sertoli cells are under the control of follicle-stimulating hormone (FSH) and a plethora of locally produced factors (Gnessi et al., 1997). Basic fibroblast growth factor (bFGF), which belongs to the family of locally produced peptides, regulates several biological processes in a wide range of tissues and organs including the testis (Han et al., 1993). We have previously observed that FSH and bFGF regulate several mechanisms involved in lactate production in Sertoli cells (Meroni et al., 2002, Riera et al., 2002, Riera et al., 2003). However, the possible participation of these hormones in the regulation of FA metabolism and in mitochondrial biogenesis in Sertoli cells has not been analyzed yet. Recently, we have observed that pharmacological PPARα and PPARβ/δ activation regulates the expression of genes involved in FA metabolism such as FAT/CD36, CPT1, LCAD and MCAD in Sertoli cells. We have also observed that PPARβ/δ activation can simultaneously regulate the expression of the above-mentioned genes and lactate production. These results were interpreted as a reflection of a coordinated mechanism which will ensure the concomitant provision of energy to Sertoli and germ cells (Regueira et al., 2014). The mechanisms involved in a possible activation of this nuclear receptor under physiological conditions, which may include hormonal regulation, have not been analyzed yet in Sertoli cells.