Metabolic Effects of L-Carnitine on Prepubertal Rat Sertoli Cells

Abstract

The role of carnitine on Sertoli cell metabolism was investigated. Carnitine effects on Sertoli cell lipid metabolism were evaluated by measuring the intracellular levels of non-esterified fatty acids (NEFA) and ketone bodies. The concentration of NEFA in Sertoli cell cultured in the presence of carnitine is significantly reduced as compared to control, while, no significant changes were observed in the concentration of ketone bodies. The functional parameters evaluated to assess the influence of carnitine on Sertoli cell carbohydrate metabolism, i.e., lactate and pyruvate production, lactate dehydrogenase activity and hexose transport, were all significantly increased following carnitine in vitro supplementation. Thus, carnitine appears to drive Sertoli cell intermediary metabolism in an intimately interrelated way, stimulating both fatty acid breakdown and glycolysis. Our results indicate that Sertoli cells are a possible target for a widespread metabolic action of carnitine and strongly support the involvement of carnitine in the regulation of Sertoli cell functions which are related with germ cell "nutrition", convincingly suggesting a direct influence of the compound at testis level.

Carnitine partially protects the rat testis against the late damage produced by doxorubicin administered during pre‐puberty

“…In this study, it is likely that part of the protective action provided by carnitine to the seminiferous epithelium was mediated by Sertoli cells, by maintaining the blood-testis barrier function, as the Sertoli cells express OCTN2, the Carnitine/ Organic Cation Transporter 2, commonly found in blood-tissue barriers (Kobayashi et al 2005). Indeed, Palmero et al (2000) demonstrated that carnitine acts directly on the Sertoli cells in vitro, improving their physiology and, consequently, germ cell development and maturation. Nevertheless, this issue still deserves further investigation.…”

“…Our results indicate that, indeed, doxorubicin causes damage to sperm DNA and that carnitine anyhow maintains its integrity. Palmero et al (2000) also showed that exogenous carnitine might act as a cellular protector through the stimulation of DNA repair by serving as an extra source of acetyl group to the coenzyme A, by increasing cellular energy metabolism and favoring DNA repair and germ cell development. In addition, carnitine may operate through a mechanism likely involved in the inhibition of ceramides production; such characteristic reasserts carnitine as a promising cytoprotector, capable of avoiding the cellular depletion caused by chemotherapy (Andrieu-Abadie et al, 1999).…”

“…It acts on male gamete maturation (Ng et al, 2004) and seems to have a role in the production of energy for sperm motility. Besides, carnitine is also involved in DNA repair (Garcia et al, 2005), germ cell recovery (Tarladacalisir et al, 2009) and Sertoli cell metabolism (Palmero et al, 2000). Waldner et al (2006) showed that high plasmatic carnitine levels following supplementation with L-carnitine induce the upregulation of enzymes involved in the fatty acid (FA) metabolism in doxorubicin-treated patients with non-Hodgkin lymphoma, providing evidences that doxorubicin-induced blockage of L-carnitine uptake may be attenuated by L-carnitine treatment.…”

OCTN2-mediated transport of carnitine in isolated Sertoli cells

“…5b), suggesting that carnitine can be passed from the blood circulation to Sertoli cells, as well as germ cells. This speculation was supported by the findings that oxidation of fatty acids is likely to be the major energy source for Sertoli cells (Jutte et al 1985) and that L-carnitine treatment significantly reduced non-esterified fatty acids in cultured rat Sertoli cells (Palmero et al 2000).…”

Carnitine reduces testicular damage in rats treated with etoposide in the prepubertal phase

“…Because of its antioxidant properties, carnitine has been used in the treatment of male infertility (Vicari et al 2002;Lenzi et al 2003) and as a cytoprotective substance against the toxicity of drugs such as alcohol and bleomycin (Arafa and Sayed-Ahmed 2003;Demirdag et al 2004;Sayed-Ahmed et al 2004). Moreover, Palmero et al (2000) have demonstrated that carnitine acts directly on the Sertoli cells in vitro, improving their physiology and, consequently, the development of the germ cells. In view of the therapeutic, antioxidant, and cytoprotective properties of carnitine in other tissues, we have investigated whether carnitine protects rat testes against etoposide and, thus, improves fertility in adulthood.…”