Sphingolipids are bioactive lipids that can modulate insulin sensitivity, cellular differentiation, and apoptosis in a tissue-specific manner. However, their comparative profiles in bovine retroperitoneal (RPAT) and subcutaneous adipose tissue (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 and quantified by UPLC-MS/MS in multiple reaction monitoring (MRM) mode, including ceramide (Cer), dihydroceramide (DHCer), sphingomyelin (SM), dihydrosphingomyelin (DHSM), ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), galactosylceramide (GalCer), glucosylceramide (GluCer), lactosylceramide (LacCer), sphinganine (DHSph), and sphingosine (Sph). 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, thereby increasing the concentration of further sphingolipid intermediates in the de novo synthesis pathway. This distinctive sphingolipid distribution pattern in RPAT and SCAT can potentially explain the tissue-specific activity in insulin sensitivity, proinflammation, and oxidative stress in RPAT and SCAT.
Background: Sphingolipids modulate insulin sensitivity in mammals. Increased synthesis of ceramides is linked to decreased insulin sensitivity of tissues. Conversely, activation of the insulin signaling pathway can downregulate ceramide synthesis. Elucidating the association between sphingolipid metabolism and insulin response during oral glucose testing may help explain the pathophysiology of insulin dysregulation in horses.Hypotheses: Horses with insulin dysregulation will have a plasma sphingolipid profile characterized by increased ceramide concentrations. The plasma sphingolipid profile will have decreased ceramide concentrations after acute activation of the insulin signaling pathway by oral glucose testing. Animals: Twelve Icelandic horses.Methods: Horses were subjected to an oral glucose test (0.5 g/kg body weight glucose), with plasma insulin concentrations measured at 0, 30, 60, 120, 180, and 240 minutes postglucose administration. Plasma samples were collected at 0 and 120 minutes for sphingolipid profiling using a liquid chromatography-mass spectrometry-based metabolomics analysis. Eighty-three species of sphingolipids were detected, including 3-ketosphinganines, dihydroceramides, ceramides, dihydrosphingomyelins, sphingomyelins, galatosylceramides, glucosylceramides, lactosylceramides, and ceramide-1-phosphates.
Insulin dysregulation (ID) is a determinant of equine metabolic syndrome. Among the sphingolipids, ceramides contribute to the development of ID; however, the crosstalk between the liver and adipose tissue (AT) depots and the variation among AT depots in terms of ceramide metabolism are not well-understood. We aimed to characterize the sphingolipidome of plasma, liver, and AT (nuchal, NUAT; subcutaneous, SCAT; omental, OMAT; retroperitoneal, RPAT) and their associations with insulin response to oral glucose testing (OGT) in normoinsulinemic and hyperinsulinemic horses. Plasma, liver, and AT samples were collected from 12 Icelandic horses upon euthanasia and analyzed by liquid chromatography-mass spectrometry. Eighty-four targeted compounds were effectively quantified. Comparing the AT depots, greater (FDR < 0.05) ceramide, dihydroceramide, and sphingomyelin concentrations and lower glucosyl- and galactosyl-ceramides were found in RPAT and OMAT than in NUAT and SCAT. Hyperinsulinemic response to OGT was associated with sphingolipidome alterations primarily in the RPAT and OMAT, while the NUAT sphingolipidome did not show signs of ceramide accumulation, which was inconsistent with the previously proposed role of nuchal adiposity in ID. The plasma sphingolipidome was not significantly associated with the liver or AT sphingolipidomes, indicating that plasma profiles are determined by an interplay of various organs. Further, hepatic sphingolipid profiles were not correlated with the profiles of AT depots. Finally, statistically valid partial least square regression models predicting insulin response were found in the plasma (Q2= 0.58, R2= 0.98), liver (Q2= 0.64, R2= 0.74), and RPAT (Q2= 0.68, R2= 0.79) sphingolipidome, but not in the other adipose tissues.
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.
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