Sphingolipid Profiling Reveals Different Extent of Ceramide Accumulation in Bovine Retroperitoneal and Subcutaneous Adipose Tissues

Leung, Yue Hei; Bäßler, Sonja Christiane; Koch, Christian; Scheu, Theresa; Meyer, Ulrich; Dänicke, Sven; Huber, Korinna; Kenéz, Ákos

doi:10.3390/metabo10110473

Cited by 9 publications

(8 citation statements)

References 46 publications

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“…Sphingolipids of the de novo synthesis pathway, such as sphinganine, dihydroceramide, and Cer, were more concentrated in RPAT than in SCAT [90]. Sphingolipids of the salvage pathway and the sphingomyelinase pathway, such as SPH, S1P, ceramide-1-phosphate, glycosphingolipid, and SM, were more concentrated in SCAT [90]. This unique distribution of sphingolipids may contribute to differences in insulin sensitivity, inflammation, and oxidative stress between RPAT and SCAT in cows with SCK.…”

Section: Discussionmentioning

confidence: 90%

“…Leung et al [90] observed variations in sphingolipid compositions between bovine RPAT and SCAT, notably finding higher ceramide levels in RPAT than in SCAT. Sphingolipids of the de novo synthesis pathway, such as sphinganine, dihydroceramide, and Cer, were more concentrated in RPAT than in SCAT [90]. Sphingolipids of the salvage pathway and the sphingomyelinase pathway, such as SPH, S1P, ceramide-1-phosphate, glycosphingolipid, and SM, were more concentrated in SCAT [90].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, RPAT shows a higher expression of proinflammatory cytokines and chemokines at the mRNA level under conditions of energy surplus [88]. Leung et al [90] observed variations in sphingolipid compositions between bovine RPAT and SCAT, notably finding higher ceramide levels in RPAT than in SCAT. Sphingolipids of the de novo synthesis pathway, such as sphinganine, dihydroceramide, and Cer, were more concentrated in RPAT than in SCAT [90].…”

Section: Discussionmentioning

confidence: 99%

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Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective

Zhao,

Li,

Tan

et al. 2024

Antioxidants

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Ketosis, especially its subclinical form, is frequently observed in high-yielding dairy cows and is linked to various diseases during the transition period. Although adipose tissue plays a significant role in the development of metabolic disorders, its exact impact on the emergence of subclinical ketosis (SCK) is still poorly understood. The objectives of this study were to characterize and compare the profiling of transcriptome and lipidome of blood and adipose tissue between SCK and healthy cows and investigate the potential correlation between metabolic disorders and lipid metabolism. We obtained blood and adipose tissue samples from healthy cows (CON, n = 8, β-hydroxybutyric acid concentration < 1.2 mmol/L) and subclinical ketotic cows (SCK, n = 8, β-hydroxybutyric acid concentration = 1.2–3.0 mmol/L) for analyzing biochemical parameters, transcriptome, and lipidome. We found that serum levels of nonesterified fatty acids, malonaldehyde, serum amyloid A protein, IL-1β, and IL-6 were higher in SCK cows than in CON cows. Levels of adiponectin and total antioxidant capacity were higher in serum and adipose tissue from SCK cows than in CON cows. The top enriched pathways in whole blood and adipose tissue were associated with immune and inflammatory responses and sphingolipid metabolism, respectively. The accumulation of ceramide and sphingomyelin in adipose tissue was paralleled by an increase in genes related to ceramide biosynthesis, lipolysis, and inflammation and a decrease in genes related to ceramide catabolism, lipogenesis, adiponectin production, and antioxidant enzyme systems. Increased ceramide concentrations in blood and adipose tissue correlated with reduced insulin sensitivity. The current results indicate that the lipid profile of blood and adipose tissue is altered with SCK and that certain ceramide species correlate with metabolic health. Our research suggests that disruptions in ceramide metabolism could be crucial in the progression of SCK, exacerbating conditions such as insulin resistance, increased lipolysis, inflammation, and oxidative stress, providing a potential biomarker of SCK and a novel target for nutritional manipulation and pharmacological therapy.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective

Zhao,

Li,

Tan

et al. 2024

Antioxidants

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“…The sphingolipid metabolome was quantified by a targeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics assay in the liver, muscle, and subcutaneous adipose tissue samples. This analysis was carried out at the UVic Node of The Metabolomics Innovation Centre (TMIC; Genome BC Proteomics Centre, The University of Victoria, Victoria, BC, Canada) following the previously published workflow ( Leung et al, 2020 ). The 77 compounds targeted herein belonged to the following sphingolipid classes: 3-keto-sphinganine (3-KSpha), sphinganines (Spha), sphinganine-1-phosphates (Spha-P), dihydroceramides (dhCer), dihydroceramide-1-phosphates (dhCer-P), ceramides (Cer), ceramide-1-phosphates (Cer-P), galactosyl-ceramides (GalCer), glucosyl-ceramides (GlcCer), lactosyl-ceramides (LacCer), sphingomyelins (SM), dihydrosphingomyelins (dhSM), and sphingosines (Spho).…”

Section: Methodsmentioning

confidence: 99%

Ceramide metabolism associated with chronic dietary nutrient surplus and diminished insulin sensitivity in the liver, muscle, and adipose tissue of cattle

et al. 2022

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High dietary energy and protein supply is common practice in livestock nutrition, aiming to maximize growth and production performance. However, a chronic nutritional surplus induces obesity, promotes insulin insensitivity, and triggers low-grade inflammation. Thirty Holstein bulls were randomly assigned to two groups, low energy and protein (LEP), and high energy and protein (HEP) intake, provided from the 13th to the 20th month of life. Body weight, carcass composition, laminitis score, and circulating insulin and glucose concentrations were assessed. The expression and extent of phosphorylation of insulin signaling proteins were measured in the liver, muscle, and adipose tissue. The sphingolipid metabolome was quantified by a targeted liquid chromatography-mass spectrometry based metabolomics approach. The HEP bulls were obese, had hyperinsulinemia with euglycemia, and expressed clinical signs of chronic laminitis. In the liver, protein kinase B (PKB) phosphorylation was decreased and this was associated with a higher tissue concentration of ceramide 16:0, a sphingolipid that diminishes insulin action by dephosphorylating PKB. In the adipose tissue, insulin receptor expression was lower in HEP bulls, associated with higher concentration of hexosylceramide, which reduces the abundance of functional insulin receptors. Our findings confirm that diet-induced metabolic inflammation triggers ceramide accumulation and disturbs insulin signaling. As insulin insensitivity exacerbates metabolic inflammation, this self-reinforcing cycle could explain the deterioration of metabolic health apparent as chronic laminitis. By demonstrating molecular relationships between insulin signaling and sphingolipid metabolism in three major tissues, our data extend our mechanistic understanding of the role of ceramides in diet-induced metabolic inflammation.

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“…Equine plasma samples, collected at 0 and 120 minutes, relative to glucose administration, were used for sphingolipid analysis at The Metabolomic Innovation Centre (TMIC UVic Node at The University of Victoria, Genome BC Proteomics Centre, Victoria, British Colombia, Canada), as reported previously. 24 Briefly, 50 μL of sample were mixed with 0.95 mL of methanol‐chloroform (5:2), including 0.1 mg/mL of butylated hydroxytoluene as antioxidant. The sample mixtures then were vortexed for 30 seconds, sonicated for 5 minutes in an ice bath, and centrifuged for 20 minutes at 21 000 g at 10°C to precipitate proteins.…”

Section: Methodsmentioning

confidence: 99%

Associations of plasma sphingolipid profiles with insulin response during oral glucose testing in Icelandic horses

Leung

Kenéz

Grob

et al. 2021

Veterinary Internal Medicne

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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.

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Sphingolipid Profiling Reveals Different Extent of Ceramide Accumulation in Bovine Retroperitoneal and Subcutaneous Adipose Tissues

Cited by 9 publications

References 46 publications

Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective

Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective

Ceramide metabolism associated with chronic dietary nutrient surplus and diminished insulin sensitivity in the liver, muscle, and adipose tissue of cattle

Associations of plasma sphingolipid profiles with insulin response during oral glucose testing in Icelandic horses

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