The Warburg Effect Revisited—Lesson from the Sertoli Cell

Abstract

Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient. Since Warburg’s pioneering works, special attention has been given to this difference in cell metabolism. The Warburg effect has been implicated in cell transformation, immortalization, and proliferation during tumorigenesis. Cancer cells display enhanced glycolytic activity, which is correlated with high proliferation, and thus, glycolysis appears to be an excellent candidate to target cancer cells. Nevertheless, little attention has been given to noncancerous cells that exhibit a “Warburg-like” metabolism with slight, but perhaps crucial, alterations that may provide new directions to develop new and effective anticancer therapies. Within the testis, the somatic Sertoli cell (SC) presents several common metabolic features analogous to cancer cells, and a clear “Warburg-like” metabolism. Nevertheless, SCs actively proliferate only during a specific time period, ceasing to divide in most species after puberty, when they become terminally differentiated. The special metabolic features of SC, as well as progression from the immature but proliferative state, to the mature nonproliferative state, where a high glycolytic activity is maintained, make these cells unique and a good model to discuss new perspectives on the Warburg effect. Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg effect and cell proliferation.

Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea

“…The Sertoli cells (SCs) are responsible for the production of metabolic precursors essential for germ cells development [20]. These cells show a "Warburg-like effect" metabolism [21], using the external glucose to produce lactate, which is the preferred substrate of developing germ cells [22].…”

Novel molecular mechanisms involved in hormonal regulation of lactate production in Sertoli cells

“…Even though Sertoli cells do not proliferate after puberty, these cells in the testis present similar metabolic characteristics to those observed in cancer cells. Consequently, Sertoli cells have been recently proposed as a useful model to revisit the 'Warburg effect' (Oliveira et al 2015).…”

Impact of DNA mismatch repair system alterations on human fertility and related treatments

“…This indicates that defects in MMR may underlie some forms of male infertility such as Sertoli cell-only, hypospermatogenesis type, and maturation arrest. Recently, Sertoli cells have been recognized as having several common metabolic features analogous to those of cancer cells and could be used as a good model for exploring new perspectives of the Warburg effect (Oliveira et al, 2015). Sertoli cells may play a significant role in obesity-induced male infertility .…”