Sphingolipid serum profiling in vitamin D deficient and dyslipidemic obese dimorphic adults

Al-Daghri, Nasser M.; Torretta, Enrica; Barbacini, Pietro; Asare, Hannah; Ricci, Cristian; Capitanio, Daniele; Guerini, Franca Rosa; Sabico, Shaun; Alokail, Majed S.; Clerici, Mario; Gelfi, Cecilia

doi:10.1038/s41598-019-53122-4

Cited by 15 publications

(15 citation statements)

References 61 publications

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“…In line with our results, changes in specific chains abundance appear to be a common trait of viral infections and of their outcome. The risk of death from COVID-19 is about 10 times higher in countries where most of the population is overweight (COVID-19 and Obesity: The 2021 Atlas) and previous studies from our group highlighted the role of acyl chain composition in bodily fluids in obesity and obesity-related comorbidities [ 36 , 37 , 38 ]. In obese subjects, high levels of total Cers, lower levels of total SM, and of DhSM compared to normolipidemic normal weight controls were found.…”

Section: Discussionmentioning

confidence: 90%

Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature

Torretta

Garziano

Poliseno

et al. 2021

IJMS

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The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient’s outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.

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Section: Discussionmentioning

confidence: 90%

Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature

Torretta

Garziano

Poliseno

et al. 2021

IJMS

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“…Ceramide is the central hub, acting as a second messenger in cellular signaling pathways with beneficial or detrimental effects for cell survival [ 4 , 5 , 6 ]. In biological fluids, abundance of SLs is sex-specific and characterizes dementia, cardiovascular diseases (CVD), diabetes (T2DM), obesity, susceptibility to viral infections and osteoporosis [ 7 , 8 , 9 , 10 , 11 , 12 ]. In physiology, the comparative assessment of SL levels made it possible to reveal changes in aging, identifying molecules potentially able to predict a better trajectory of aging or evolution toward CVD, T2DM [ 13 , 14 ] or disabilities as osteoarthritis [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Insight into the Serum Sphingolipid Fingerprint Characterizing Longevity

Barbacini

Torretta

Arosio

et al. 2022

IJMS

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Sphingolipids (SLs) are structural components of the lipid bilayer regulating cell functions. In biological fluids, their distribution is sex-specific and is at variance in aging and many disorders. The aim of this study is to identify SL species associated with the decelerated aging of centenarians. SLs, extracted from serum of adults (Ad, 35–37 years old), aged (Ag, 75–77 years old) and centenarian (C, 105–107 years old) women were analyzed by LC-MS/MS in combination with mRNA levels in peripheral blood mononuclear cells (PBMCs) of SL biosynthetic enzymes. Results indicated in Ag and C vs. Ad a comparable ceramides (Cers) increase, whereas dihydroceramide (dhCer) decreased in C vs. Ad. Hexosylceramides (HexCer) species, specifically HexCer 16:0, 22:0 and 24:1 acyl chains, increased in C vs. Ag representing a specific trait of C. Sphingosine (Sph), dihydrosphingosine (dhSph), sphingosine-1-phosphate (S1P) and dihydrosphingosine-1-phosphate (dhS1P), increased both in Ag and C vs. Ad, with higher levels in Ag, indicating a SL fine-tuning associated with a reduced physiological decline in C. mRNA levels of enzymes involved in ceramide de novo biosynthesis increased in Ag whereas enzymes involved in sphingomyelin (SM) degradation increased in C. Collectively, results suggest that Ag produce Cers by de novo synthesis whereas C activate a protective mechanism degrading SMs to Cers converting it into glycosphingolipids.

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“…Dysfunctional organelles promote the release of FFAs and their intermediates (e.g., diacylglycerol, linoleic, phosphatidic and lysophosphatidic acids and ceramides), proinflammatory molecules and ROS. The increase of these molecules in the bloodstream [ 17 , 18 ] can develop a low-grade systemic inflammation that determines the onset of insulin resistance [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Skeletal Muscle Proteomic Profile Revealed Gender-Related Metabolic Responses in a Diet-Induced Obesity Animal Model

Moriggi

Belloli

Barbacini

et al. 2021

IJMS

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Obesity is a chronic, complex pathology associated with a risk of developing secondary pathologies, including cardiovascular diseases, cancer, type 2 diabetes (T2DM) and musculoskeletal disorders. Since skeletal muscle accounts for more than 70% of total glucose disposal, metabolic alterations are strictly associated with the onset of insulin resistance and T2DM. The present study relies on the proteomic analysis of gastrocnemius muscle from 15 male and 15 female C56BL/J mice fed for 14 weeks with standard, 45% or 60% high-fat diets (HFD) adopting a label-free LC–MS/MS approach followed by bioinformatic pathway analysis. Results indicate changes in males due to HFD, with increased muscular stiffness (Col1a1, Col1a2, Actb), fiber-type switch from slow/oxidative to fast/glycolytic (decreased Myh7, Myl2, Myl3 and increased Myh2, Mylpf, Mybpc2, Myl1), increased oxidative stress and mitochondrial dysfunction (decreased respiratory chain complex I and V and increased complex III subunits). At variance, females show few alterations and activation of compensatory mechanisms to counteract the increase of fatty acids. Bioinformatics analysis allows identifying upstream molecules involved in regulating pathways identified at variance in our analysis (Ppargc1a, Pparg, Cpt1b, Clpp, Tp53, Kdm5a, Hif1a). These findings underline the presence of a gender-specific response to be considered when approaching obesity and related comorbidities.

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Sphingolipid serum profiling in vitamin D deficient and dyslipidemic obese dimorphic adults

Cited by 15 publications

References 61 publications

Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature

Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature

Novel Insight into the Serum Sphingolipid Fingerprint Characterizing Longevity

Skeletal Muscle Proteomic Profile Revealed Gender-Related Metabolic Responses in a Diet-Induced Obesity Animal Model

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