Ganglioside <scp>GM3</scp> content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: <scp>I</scp>mplications of glycosphingolipid metabolism in pathophysiology of diabetes

Božić, Joško; Markotić, Alemka; Čulić, Vedrana Čikeš; Novak, Anita; Borovac, Josip Anđelo; Vučemilović, Hrvoje; Trgo, Gorana; Kurir, Tina Tičinović

doi:10.1111/1753-0407.12569

Cited by 16 publications

(9 citation statements)

References 64 publications

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“…Rats fed a high-fat, obesogenic diet for 12 weeks had an accumulation of hexosylceramides in adipose tissue but a depletion in muscle (27). However, in rodent diabetes models, it was found that muscle hexosylceramide levels increased in a T2DM model but decreased in a T1DM model (28). In the current study, we identified only 1 GM3 species (d18:1/16:0).…”

Section: L I N I C a L M E D I C I N Ementioning

confidence: 43%

Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence

Chew¹,

Torta²,

Ji³

et al. 2019

JCI Insight

110

109

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BACKGROUND. Sphingolipids (SPs) are ubiquitous, structurally diverse molecules that include ceramides, sphingomyelins (SMs), and sphingosines. They are involved in various pathologies, including obesity and type 2 diabetes mellitus (T2DM). Therefore, it is likely that perturbations in plasma concentrations of SPs are associated with disease. Identifying these associations may reveal useful biomarkers or provide insight into disease processes. METHODS. We performed a lipidomics evaluation of molecularly distinct SPs in the plasma of 2302 ethnically Chinese Singaporeans using electrospray ionization mass spectrometry coupled with liquid chromatography. SP profiles were compared to clinical and biochemical characteristics, and subjects were evaluated with follow-up visits for 11 years. RESULTS. We found that ceramides correlated positively but hexosylceramides correlated negatively with BMI and homeostatic model assessment of insulin resistance (HOMA-IR). Furthermore, SPs with a d16:1 sphingoid backbone correlated more positively with BMI and HOMA-IR, while d18:2 SPs correlated less positively, relative to canonical d18:1 SPs. We also found that higher concentrations of 2 distinct SMs were associated with a higher risk of T2DM (HR 1.45 with 95% CI 1.18-1.78 for SM d16:1/18:0 and HR 1.40 with 95% CI 1.17-1.68 for SM d18:1/18:0). CONCLUSIONS. We identified significant associations between SPs and obesity/T2DM characteristics, specifically, those of hexosylceramides, d16:1 SPs, and d18:2 SPs. This suggests that the balance of SP metabolism, rather than ceramide accumulation, is associated with the pathology of obesity. We further identified 2 specific SPs that may represent prognostic biomarkers for T2DM.

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Section: L I N I C a L M E D I C I N Ementioning

confidence: 43%

Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence

Chew¹,

Torta²,

Ji³

et al. 2019

JCI Insight

110

109

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“…Thus, incorporating HFD and STZ simulates not only the phenotype, but also the pathogenesis of human T2DM. This has made it a widely recognized method for induction of T2DM in rats (Reed et al, 2000;Flanagan et al, 2008; Liu et al, 2015;Bozic et al, 2018). By feeding an HFD for four weeks and administering STZ at a dose of 35 mg/kg, we successfully created a T2DM model in the rat.…”

Section: Discussionmentioning

confidence: 99%

IGF-1R/β-catenin signaling axis is involved in type 2 diabetic osteoporosis

Zhang

Ren

Wang

et al. 2019

J. Zhejiang Univ. Sci. B

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Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.

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“…In particular, decreased plasma levels of very long-chain ceramide were associated with a significantly lower frequency of developing diabetes-related nephropathy and macroalbuminuria. Moreover, the reduction of sphingolipids containing fatty acid C24:1 was demonstrated and associated with a reduction in cardio-and neuro-protection [7,9].…”

Section: Type 1 Diabetesmentioning

confidence: 99%

“…The role of S1P in inflammation and pathogenesis is not easy to understand. Autoimmune diabetes and especially its complications were associated with a dysmetabolism in the sphingolipids [7,9]. In particular, decreased plasma levels of very long-chain ceramide were associated with a significantly lower frequency of developing diabetes-related nephropathy and macroalbuminuria.…”

Section: Type 1 Diabetesmentioning

confidence: 99%

Functional Lipids in Autoimmune Inflammatory Diseases

Dei

Roda

et al. 2020

IJMS

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Lipids are apolar small molecules known not only as components of cell membranes but also, in recent literature, as modulators of different biological functions. Herein, we focused on the bioactive lipids that can influence the immune responses and inflammatory processes regulating vascular hyperreactivity, pain, leukocyte trafficking, and clearance. In the case of excessive pro-inflammatory lipid activity, these lipids also contribute to the transition from acute to chronic inflammation. Based on their biochemical function, these lipids can be divided into different families, including eicosanoids, specialized pro-resolving mediators, lysoglycerophospholipids, sphingolipids, and endocannabinoids. These bioactive lipids are involved in all phases of the inflammatory process and the pathophysiology of different chronic autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, type-1 diabetes, and systemic lupus erythematosus.

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Ganglioside GM3 content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: Implications of glycosphingolipid metabolism in pathophysiology of diabetes

Abstract: The expression patterns of GM3 ganglioside and its precursors in diabetic rats suggest that the role of glycosphingolipid metabolism may differ between T2DM and T1DM.

Cited by 16 publications

References 64 publications

Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence

Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence

IGF-1R/β-catenin signaling axis is involved in type 2 diabetic osteoporosis

Functional Lipids in Autoimmune Inflammatory Diseases

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