Sphingolipid Profiling Reveals Different Extent of Ceramide Accumulation in Bovine Retroperitoneal and Subcutaneous Adipose Tissues : [Preprint]

Background: Sphingolipids are bioactive lipids that can modulate insulin sensitivity, cellular differentiation, and apoptosis in a tissue-specific manner. Previous studies in dairy cattle reported that the retroperitoneal adipose tissue (RPAT) was more active than the subcutaneous adipose tissue (SCAT) in terms of insulin sensitivity, lipolytic activity, and pro-inflammatory signaling. Sphingolipids were discussed to be involved in inflammation, however, their comparative profiles in bovine RPAT and SCAT are currently unknown. We aimed to characterize the sphingolipid profiles using a targeted lipidomics approach and to assess whether potentially related sphingolipid pathways are different between SCAT and RPAT. Holstein bulls (n = 6) were slaughtered, and SCAT and RPAT samples were collected for sphingolipid profiling. A total of 70 sphingolipid species were detected, including 24 species of ceramide (Cer) and dihydroceramide (DHCer), 18 species of sphingomyelin (SM) and dihydrosphingomyelin (DHSM), 11 species of ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P), 9 species of galactosylceramide (GalCer), glucosylceramide (GluCer), lactosylceramide (LacCer), and 8 species of sphinganine (DHSph) and sphingosine (Sph). The concentration of each sphingolipid was quantified by UPLC-MRM/MS. Results: Our results showed that sphingolipids of the de novo synthesis pathway such as DHSph, DHCer, and Cer, were more concentrated in RPAT than in SCAT. Sphingolipids of the salvage pathway and the sphingomyelinase pathway such as Sph, S1P, C1P, glycosphingolipid, and SM were more concentrated in SCAT. Our results indicate that RPAT had a greater extent of ceramide accumulation, and thereby increased the concentration of further sphingolipid intermediates in the de novo synthesis pathway. Conclusion: This distinctive sphingolipid distribution pattern in RPAT and SCAT can potentially explain the tissue-specific activity in insulin sensitivity, pro-inflammation, and oxidative stress in RPAT and SCAT.