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American journal of physiology. Regulatory, integrative and comparative physiology2022; 323(4); R397-R409; doi: 10.1152/ajpregu.00018.2022

Sphingolipidome of plasma, liver, and adipose tissues and its association with insulin response to oral glucose testing in Icelandic horses.

Abstract: Insulin dysregulation (ID) is a determinant of equine metabolic syndrome. Among the sphingolipids, ceramides contribute to the development of ID; however, the cross talk 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 (false discovery rate, 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, whereas 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. Furthermore, 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.
Publication Date: 2022-08-08 PubMed ID: 35938687DOI: 10.1152/ajpregu.00018.2022Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research studied the presence of certain lipid compounds in the plasma, liver, and fat tissues of Icelandic horses and its connection to insulin response. It found significant variations of these compounds in different fat deposits, and established a correlation between their levels and the horses’ insulin response to glucose, particularly in horses with high insulin.

Overview of the Research

  • This study was directed towards understanding the role of a class of lipids called sphingolipids, specifically ceramides, in the development of insulin dysregulation (ID) in horses. Insulin dysregulation refers to conditions where the body’s response to insulin is not appropriate.
  • The research aimed to establish a connection between the sphingolipid composition of plasma, liver, and different adipose tissues with the insulin response to oral glucose testing in both normal and hyperinsulinemic horses.
  • The samples for this research were obtained from 12 Icelandic horses and were analyzed using liquid chromatography-mass spectrometry, a technique used to identify and quantify molecules in a mixture.

Findings of the Study

  • 84 different targeted compounds within the sphingolipid class could be effectively quantified.
  • The study discovered major differences between the fat depots in horses, in terms of their ceramide composition. Retroperitoneal and omental fat deposits showed higher levels of ceramides than nuchal and subcutaneous fat deposits.
  • Hyperinsulinemic response to oral glucose testing was linked to changes in the sphingolipid composition largely in the retroperitoneal and omental fat tissues.
  • The sphingolipid profile of plasma was found to be independent of the liver or adipose tissue sphingolipidomes, suggesting that plasma profiles are the result of the interaction of various organs.
  • The liver’s sphingolipid profile did not show correlation with the adipose tissue profiles.
  • Statistically validated models predicting insulin response could be derived from the sphingolipid profile of the plasma, liver, and retroperitoneal adipose tissue, but not with other adipose tissues.

Significance of the Study

  • This research adds to the understanding of the role of different lipid compounds in metabolic conditions like insulin dysregulation in horses-
  • It also highlights the need to consider the variations between different adipose tissues when studying their lipid composition and its impact on insulin regulation.
  • The findings may pave the way for new diagnostic approaches based on lipid profiles and help in developing therapies that modulate lipid metabolism for the management of insulin dysregulation in equines.

Cite This Article

APA
Jorge-Smeding E, Warnken T, Grob AJ, Feige K, Pudert T, Leung YH, Go YY, Kenéz Á. (2022). Sphingolipidome of plasma, liver, and adipose tissues and its association with insulin response to oral glucose testing in Icelandic horses. Am J Physiol Regul Integr Comp Physiol, 323(4), R397-R409. https://doi.org/10.1152/ajpregu.00018.2022

Publication

ISSN: 1522-1490
NlmUniqueID: 100901230
Country: United States
Language: English
Volume: 323
Issue: 4
Pages: R397-R409

Researcher Affiliations

Jorge-Smeding, Ezequiel
  • Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong Special Administrative Region, China.
Warnken, Tobias
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany.
Grob, Anne Julia
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany.
Feige, Karsten
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany.
Pudert, Tanja
  • Department of Surgery and Orthopaedics, Clinic for Horses, Faculty of Veterinary Medicine, Justus-Liebig University, Giessen, Germany.
Leung, Yue Hei
  • Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong Special Administrative Region, China.
Go, Yun Young
  • Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong Special Administrative Region, China.
Kenéz, Ákos
  • Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong Special Administrative Region, China.

MeSH Terms

  • Adipose Tissue
  • Animals
  • Ceramides
  • Glucose
  • Horses
  • Iceland
  • Insulin
  • Liver

Citations

This article has been cited 1 times.
  1. Furse S, Virtue S, Huang-Doran I, Vidal-Puig A, Chiarugi D, Stevenson PC, Snowden SG, Koulman A. Systemic analyses show that the biosynthesis and spatial distribution of fatty acids, triglycerides and lipids differed in male and female mice and humans. Open Biol 2025 Aug;15(8):250198.
    doi: 10.1098/rsob.250198pubmed: 40829644google scholar: lookup