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Many lipids, including simple sphingolipids, are known to regulate cell activation and metabolism (Gomez-Munoz et al., 1992; Gomez-Munoz, 1998; Gomez-Munoz, 2004; GomezMunoz, 2006; Hannun & Obeid, 2008; Chen et al., 2011; Hannun & Obeid, 2011) . Some of them, including sphingosine, ceramides and their phosphorylated forms, sphingosine 1phosphate (S1P) and ceramide 1-phosphate (C1P) have been described as crucial regulators of key processes that are essential for normal development, and have also been involved in the establishment and progression of different diseases (Gangoiti et al., 2008a; Arana et al., 2010). In particular, ceramides can induce cell growth arrest and cause apoptosis, when they are generated (Hannun et al., 1986; Kolesnick, 1987; Kolesnick & Hemer, 1990; Merrill & Jones, 1990; Merrill, 1991; Hannun, 1994; Kolesnick & Golde, 1994; Hannun & Obeid, 1995; Hannun, 1996; Spiegel & Merrill, 1996; Merrill et al., 1997; Kolesnick et al., 2000; Hannun & Obeid, 2002; Merrill, 2002). Nonetheless, although in general, ceramides are negative signals for cell survival, in neurons they can induce cell growth (Goodman & Mattson, 1996; Ping & Barrett, 1998; Brann et al., 1999; Song & Posse de Chaves, 2003; Plummer et al., 2005). Also, ceramides play important roles in the regulation of cell differentiation, inflammation, tumor development (Okazaki et al., 1990; Mathias et al., 1991; Dressler et al., 1992; Hannun, 1994; Kolesnick & Golde, 1994; Hannun & Obeid, 1995; Gomez-Munoz, 1998; Menaldino et al., 2003), bacterial and viral infections, and ischemia-reperfusion injury(Gulbins & Kolesnick, 2003). More recently, ceramides have been associated with insulin resistance through activation of protein phosphatase 2A and the subsequent dephosphorylation and inactivation of protein kinase B (PKB) (Schmitz-Peiffer, 2002; Adams et al., 2004; Stratford et al., 2004), and toll-like receptor 4 (TLR4)-dependent induction of inflammatory cytokines, a fact essential for TLR4-dependent insulin resistance (Holland et al., 2011).

Role of Ceramide 1-Phosphate in the Regulation of Cell Survival and Inflammation